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Jiang J, Zhan L, Jiang B, Pan J, Hong C, Chen Z, Yang L. Anticancer therapy-induced peripheral neuropathy in solid tumors: diagnosis, mechanisms, and treatment strategies. Cancer Lett 2025; 620:217679. [PMID: 40154913 DOI: 10.1016/j.canlet.2025.217679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 03/21/2025] [Accepted: 03/25/2025] [Indexed: 04/01/2025]
Abstract
Anticancer therapy-induced peripheral neuropathy (PN) is a common adverse event during the diagnosis and treatment of solid tumors. The drug class, cumulative dose, and individual susceptibility affect the incidence and severity of PN. Owing to the lack of specific biomarkers and imaging tests, the diagnostic criteria for PN remain unclear. Moreover, the available and effective clinical treatment strategies are very limited, and most of the current drugs focus on symptom management rather than fundamental reversal of the disease course. The morbidity mechanisms of PN are diverse, including direct neurotoxicity, mitochondrial dysfunction, and disruption of axonal transport. Here, we summarize the diagnosis, mechanisms, and neuroprotective strategies of PN and discuss potential intervention treatments.
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Affiliation(s)
- Jiahong Jiang
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Luying Zhan
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Boyang Jiang
- The Clinical Medical College, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Jingyi Pan
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Chaojin Hong
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Zheling Chen
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
| | - Liu Yang
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
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Emmelheinz M, Marth C, Egle D, Leitner K, Albertini C, Abdel Azim S, Feroz B, Strobel L, Brunner C. Comparison of Efficacy and Safety of Cryotherapy in Chemotherapy-Induced Peripheral Neuropathy Between Upper and Lower Extremities: Results from the Randomized CROPSI Study. Cancers (Basel) 2025; 17:1748. [PMID: 40507230 PMCID: PMC12153638 DOI: 10.3390/cancers17111748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2025] [Revised: 05/18/2025] [Accepted: 05/21/2025] [Indexed: 06/16/2025] Open
Abstract
Background/Objectives: This study aimed to demonstrate the higher efficacy of cryotherapy in temperature reduction in the upper compared to the lower extremity when used for prevention of chemotherapy-induced peripheral neuropathy (CIPN). Methods: This study was conducted between May 2020 and January 2023 at the Department of Obstetrics and Gynecology at the Medical University of Innsbruck. The analysis included all patients from the CROPSI study who received cryotherapy on their upper (UEX) and lower extremity (LEX) and had completed all assessments from start to end of chemotherapy as well as follow-up. The assessments included temperature measurements and neurological tests during CT and at follow-up after completion of CT. Results: Of the 97 patients recruited in the study, 50 completed all assessments and were therefore included in this analysis. Cryotherapy was more effective when cooling was applied to the upper extremity compared to the lower. On the upper extremity, cryotherapy achieved a cooling effect of 12.5 °C compared to 9.6 °C on the lower extremity (p < 0.001). Patients scored better in both neurological tests on their upper extremity compared to lower. Regarding side effects, there was no significant difference between upper and lower extremities. No severe side effects were reported for either location. Conclusions: Our study suggests that currently available devices for continuous cooling for cryotherapy are significantly more effective on the upper extremity.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Christine Brunner
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (M.E.)
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Kanbayashi Y, Ishikawa T, Tabuchi Y, Sugatani K, Taguchi T, Takayama K. Efficacy of compression therapy for prevention of peripheral neuropathy caused by taxane-based chemotherapy: a single-center retrospective observational study. Support Care Cancer 2025; 33:478. [PMID: 40381046 DOI: 10.1007/s00520-025-09527-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 05/06/2025] [Indexed: 05/19/2025]
Abstract
INTRODUCTION Chemotherapy-induced peripheral neuropathy (CIPN) is a significant complication of taxane-based chemotherapies that limits their clinical utility. This study evaluated the effectiveness of compression therapy using surgical gloves in preventing CIPN in various cancer types, including, but not limited to, breast cancer. PATIENTS AND METHODS Data from 603 patients who underwent taxane-based chemotherapy at a single institution between April 2018 and January 2024 were retrospectively analyzed. Variables associated with CIPN development were extracted and analyzed using uni- and multivariate ordered logistic regression models. RESULT Compression therapy was significantly associated with a reduced incidence of CIPN. Significant predictors of CIPN included lung cancer (odds ratio [OR] = 0.342, P = 0.003), number of chemotherapy cycles (OR = 1.015, P = 0.033), and use of surgical gloves (OR = 0.559, P = 0.003). CONCLUSION Compression therapy using simple, cost-effective surgical gloves appeared effective for preventing CIPN in a diverse cancer population undergoing taxane-based chemotherapy. The risk of CIPN increases with the number of chemotherapy cycles, and a lower incidence was observed among patients with lung cancer. These findings provide a foundation for future research aimed at improving patient quality of life during taxane-based chemotherapy.
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Affiliation(s)
- Yuko Kanbayashi
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan.
- Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
| | - Takeshi Ishikawa
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yusuke Tabuchi
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Pharmacy, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazuko Sugatani
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Nursing, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tetsuya Taguchi
- Department of Endocrine and Breast Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Koichi Takayama
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Cao Z, Wang Z, Yang L, Li T, Tao X, Niu X. Reshaping the immune microenvironment and reversing immunosenescence by natural products: Prospects for immunotherapy in gastric cancer. Semin Cancer Biol 2025; 110:1-16. [PMID: 39923925 DOI: 10.1016/j.semcancer.2025.02.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/25/2025] [Accepted: 02/03/2025] [Indexed: 02/11/2025]
Abstract
Gastric cancer (GC) represents a global health-care challenge. Recent progress in immunotherapy has elicited attracted considerable attention as a viable treatment option through modulating the host immune system and unleashing pre-existing immunity, which has profoundly revolutionized oncology, especially GC. Nonetheless, low clinical response and intrinsic and acquired resistance remain persistently challenging. The microenvironment of GC comprising multifarious stromal cell types has remarkable immunosuppressive elements that may impact the efficacy of immunotherapy. Immunosenescence is increasingly regarded as a factor that contributes to cancer development, remodels the tumor microenvironment and affects the efficacy of immunotherapy. Natural products are at the forefront of traditional medicine. Senotherapeutics is a class of drugs and natural products capable of delaying, preventing, or reversing the senescence process (i.e., senolytics) or suppressing senescence-associated secretory phenotype (i.e., senomorphics). Emerging evidence supports that natural products can improve the efficacy of existing immunotherapy and expand their indications in GC mainly based upon remodeling the immunosuppressive microenvironment and reversing immunosenescence. The review provides an integrated review of previously reported and ongoing clinical trials with immunotherapeutic regimens in GC and discusses current challenges. Next, we focus on natural compounds that exert anti-GC functions and possess immunomodulatory properties. More attention is paid to the potential of these natural compounds in modulating the immune microenvironment and immunosenescence. Lastly, we discuss the nanomedicine that can overcome the deficiencies of natural products. Altogether, our review suggests the enormous potential of natural compounds in GC immunotherapy, and provides an important direction for future research.
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Affiliation(s)
- Zhipeng Cao
- Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, China
| | - Zhilin Wang
- Department of Pain Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
| | - Li Yang
- Department of Anesthesiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China
| | - Tian Li
- Tianjin Key Laboratory of Acute Abdomen Disease-Associated Organ Injury and ITCWM Repair, Institute of Integrative Medicine of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China.
| | - Xueshu Tao
- Department of Pain Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
| | - Xing Niu
- Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, China.
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Ashok Kumar P, Sampat P, Sandhu M, Kumar VCS, Smith A, Paulraj S, Ghelani G, Huang D, Wang D, Sivapiragasam A. A meta-analysis of the utility of cryotherapy for preventing peripheral neuropathy among breast cancer patients receiving paclitaxel and nab-paclitaxel. Breast Cancer Res Treat 2025; 210:595-604. [PMID: 39827229 DOI: 10.1007/s10549-024-07597-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 12/21/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND Cryotherapy with taxane infusion is a noninvasive strategy for preventing peripheral neuropathy (PN), but the efficacy of this approach has not been proven. METHODS A systematic search was conducted, and 477 records were initially identified. The titles were screened independently by 2 reviewers. Fourteen studies were ultimately included for meta-analysis, which was conducted using the meta package in the R software. Only studies that analysed cryotherapy use in breast cancer patients who received paclitaxel or nab-paclitaxel were included. Relative risks (RRs) were calculated using the random effects model to compare the occurrence of PN between the paclitaxel and nab-paclitaxel groups. RESULTS The incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 PN was 24.85% (81/326) in the cryotherapy arm and 42.35% (72/170) in the placebo arm. The overall RR CTCAE grade ≥ 2 PN in the cryotherapy group compared with the placebo group was 0.45 [0.27, 0.77, p = 0.0031]. The RR for sensory PN was 0.19 [0.05, 0.66, p = 0.009], and that for motor PN was 0.18 [0.03, 0.99, p = 0.0491]. The RR for Patient Neurotoxicity Questionnaire (PNQ) scores ≥ D, which indicate severe neuropathy, was 0.24 [0.09, 0.62; p = 0.0035]. Cold intolerance was the most reported t adverse effect, with a prevalence of 15% (37/247). CONCLUSIONS The use of cryotherapy decreased the occurrence of CTCAE grade ≥ 2 PN by 55%. Cold intolerance was the most frequently reported adverse effect associated with cryotherapy, but this adverse effect did not lead to high discontinuation rates.
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Affiliation(s)
- Prashanth Ashok Kumar
- Division of Hematology-Oncology, Upstate Cancer Center, Upstate University Hospital, Syracuse, NY, USA.
- George Washington University, 2150 Pennsylvania Avenue NW, Washington, DC, 20037, USA.
| | - Parth Sampat
- Division of Hematology-Oncology, Upstate Cancer Center, Upstate University Hospital, Syracuse, NY, USA
| | - Michael Sandhu
- Department of Medicine, Upstate University Hospital, Syracuse, NY, USA
| | | | - Abigail Smith
- Health Sciences Library, Upstate University Hospital, Syracuse, NY, USA
| | - Shweta Paulraj
- Division of Cardiology, Upstate University Hospital, Syracuse, NY, USA
| | - Ghanshyam Ghelani
- Division of Hematology-Oncology, Upstate Cancer Center, Upstate University Hospital, Syracuse, NY, USA
- The University of Texas Health Science Center at Tyler, Texas, USA
| | - Danning Huang
- Department of Public Health and Preventive Medicine, Upstate University Hospital, Syracuse, NY, USA
| | - Dongliang Wang
- Department of Public Health and Preventive Medicine, Upstate University Hospital, Syracuse, NY, USA
| | - Abirami Sivapiragasam
- Division of Hematology-Oncology, Upstate Cancer Center, Upstate University Hospital, Syracuse, NY, USA
- Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA
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Kim EY, Lee MY, Suh BC. The Use of Nerve Conduction Study to Evaluate the Effects of Frozen Sock Treatment on Docetaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Prospective Clinical Trial. J Clin Med 2025; 14:864. [PMID: 39941535 PMCID: PMC11818139 DOI: 10.3390/jcm14030864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 01/21/2025] [Accepted: 01/23/2025] [Indexed: 02/16/2025] Open
Abstract
Background/Objectives: Docetaxel is a cytotoxic agent for the treatment of breast cancer, and its toxicities include peripheral neuropathy (PN). This study evaluated the ability of frozen sock (FS) treatment to prevent docetaxel-induced PN by performing nerve conduction study (NCS). Methods: From October 2017 to October 2018, 48 patients who had invasive carcinoma and were planned for docetaxel treatment every three weeks were evaluated. Patients wore a FS on the right foot, and the left foot was not protected by the FS during docetaxel infusion. Motor and sensory NCS as well as nail and skin toxicities were assessed. Results: The amplitude and velocity of the motor and sensory nerves significantly decreased after three months in both feet. Before and after three months of chemotherapy, the compound motor action potentials (CMAPs) for the right peroneal nerve were 7.64 ± 2.42 and 6.81 ± 2.21 mV, respectively (p < 0.001), and 7.13 ± 2.41 and 5.90 ± 2.24 mV, respectively (p < 0.001), for the left peroneal nerve. Reductions in the CMAP amplitude of the peroneal nerve were significantly lower in the right foot compared to the left foot (-9.58 vs. -16.8, p = 0.043). Application of the FS did not significantly decrease the overall incidence of skin and nail toxicity compared with the left foot during the study period (all p > 0.05). Conclusions: Docetaxel induced motor and sensory PN, but the use of a FS resulted in a smaller reduction in peroneal nerve amplification three months after the end of chemotherapy.
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Affiliation(s)
- Eun-Young Kim
- Department of Surgery, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 03181, Republic of Korea;
| | - Mi-Yeon Lee
- Division of Biostatistics, Department of Academic Research, Kangbuk Samsung Hospital, Seoul 03181, Republic of Korea;
| | - Bum-Chun Suh
- Department of Neurology, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 03181, Republic of Korea
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Xiaoqian Y, Jiwei H, Lizhi Z, Baojia G, Luyan G, Huiqian X, Hong L, Yijing F. A randomized controlled trial: Effects of compression therapy combined with exercise on chemotherapy-induced peripheral neuropathy in patients with breast cancer. Cancer Treat Res Commun 2025; 42:100871. [PMID: 39842054 DOI: 10.1016/j.ctarc.2025.100871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 01/14/2025] [Accepted: 01/17/2025] [Indexed: 01/24/2025]
Abstract
PURPOSE To investigate the effects of compression therapy combined with exercise for cancer patients (EXCAP) in patients with peripheral neuropathy caused by breast cancer chemotherapy. METHODS Overall, 108 patients with peripheral neuropathy after chemotherapy for breast cancer were randomly divided into the control group (routine nursing), experimental group 1 (compression therapy), and experimental group 2 (compression therapy and EXCAP). The National Institute of Cancer Drug Toxicity Rating Scale and the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool were assessed and compared between groups. RESULTS The incidence of grade 0 peripheral neuropathy in both experimental groups was higher than that in controls (P < 0.001), and the incidence in group 2 was higher than that in group 1 (P < 0.001). The incidence of grade 2 disease in both experimental groups was lower than that in controls (P < 0.001). The rate of symptoms in both experimental groups after the intervention were lower than that in the control group (P < 0.001), and those in experimental group 2 were lower than those in experimental group 1 (P < 0.001). Scores regarding activities of daily living in the experimental groups were lower than those of the control group (P < 0.001), and lower in group 2 than in group 1 (P < 0.001). CONCLUSION Compression therapy and EXCAP can effectively reduce the incidence of chemotherapy-induced peripheral neuropathy in patients undergoing breast cancer chemotherapy. They can both positively impact patients' daily lives and symptom experiences; however, they are more effective when combined.
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Affiliation(s)
- Yu Xiaoqian
- North China University of Science and Technology, Tangshan 063210, China
| | - Hu Jiwei
- Tangshan People's Hospital, Tangshan 063000, China
| | - Zhou Lizhi
- Tangshan People's Hospital, Tangshan 063000, China.
| | - Guo Baojia
- Tangshan People's Hospital, Tangshan 063000, China
| | - Guo Luyan
- North China University of Science and Technology, Tangshan 063210, China
| | - Xu Huiqian
- North China University of Science and Technology, Tangshan 063210, China
| | - Li Hong
- North China University of Science and Technology, Tangshan 063210, China
| | - Fan Yijing
- North China University of Science and Technology, Tangshan 063210, China
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Ozdemir D, Arslan S, Artac M, Karaarslan F. Topical menthol for chemotherapy-induced peripheral neuropathy: a randomised controlled trial in breast cancer. BMJ Support Palliat Care 2024; 15:79-86. [PMID: 39038990 DOI: 10.1136/spcare-2023-004483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 06/12/2024] [Indexed: 07/24/2024]
Abstract
OBJECTIVES Chemotherapy-induced peripheral neuropathy (CIPN) symptom is one of the side effects of paclitaxel in breast cancer patients. This randomised controlled study was conducted to investigate the effect of topical menthol applied on the hands and feet of breast cancer patients receiving chemotherapy on CIPN symptoms. METHODS 60 breast cancer patients receiving chemotherapy were randomly assigned to an intervention group (n=30), which received topical menthol treatment, or a control group (n=30), which received standard care. Both groups continued their routine pharmacological treatments throughout the study. The intervention group applied 1% menthol topically to their hands and feet two times a day. The effect of the intervention on CIPN symptoms was evaluated 3 weeks and 6 weeks after the intervention. RESULTS The intervention group showed a significantly greater improvement in CIPN symptoms over time compared with the control group, with an effect size of η2=0.214 for the group×time interaction. Additionally, the intervention group exhibited a notable positive change in the exposure subscale of the CIPN rating scale, with an effect size of η2=0.114. CONCLUSIONS Topical application of menthol significantly mitigates the symptoms of CIPN in breast cancer patients. This study supports the use of menthol as an effective adjunctive treatment for CIPN. TRIAL REGISTRATION NUMBER NCT05429814.
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Affiliation(s)
| | - Selda Arslan
- Department of Internal Medicine Nursing, Necmettin Erbakan University, Nursing Faculty, Meram, Turkey
| | - Mehmet Artac
- Department of Medical Oncology, Necmettin Erbakan University Meram Faculty of Medicine, Meram, Turkey
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Brunner C, Emmelheinz M, Egle D, Ritter M, Leitner K, Wieser V, Albertini C, Abdel Azim S, Mutz-Dehbalaie I, Kögl J, Marth C. Cropsi study: Efficacy and safety of cryotherapy and cryocompression in the prevention of chemotherapy-induced peripheral neuropathy in patients with breast and gynecological cancer-A prospective, randomized trial. Breast 2024; 76:103763. [PMID: 38941655 PMCID: PMC11260371 DOI: 10.1016/j.breast.2024.103763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 06/01/2024] [Accepted: 06/25/2024] [Indexed: 06/30/2024] Open
Abstract
OBJECTIVE This study aimed to demonstrate the superiority of cryocompression over cryotherapy alone in the prevention of chemotherapy-induced peripheral neuropathy (CIPN) grade 2 or above. METHODS This prospective randomized study was conducted between May 2020 and January 2023 in Innsbruck. Eligible patients had a diagnosis of gynecological cancer and received a minimum of 3 cycles of taxane-based CT (neoadjuvant, adjuvant or palliative therapy). Patients were randomized 1:1 to receive either cryotherapy or cryocompression on their upper extremities during chemotherapy (CT). We performed temperature measurements, two QoL questionnaires and neurological tests during CT and at follow-up 3 and 6-9 months after the completion of CT. CIPN was assessed using the CTCAE score. RESULTS Of 200 patients recruited, both groups showed a lower prevalence of CIPN in this study compared to recent literature. In the group receiving cryotherapy, the prevalence of grade 1 CIPN was 30.1 %, and that of grade 2 CIPN or above was 13.7 %; in the group treated with cryocompression, the prevalence of grade 1 CIPN was 32.8 %, and that of grade 2 or above CIPN was 17.2 %. We found a significant reduction in temperature in the cryotherapy and cryocompression groups. Regarding the two QOL questionnaires as well as the neurological tests no significant differences were found between the two groups. CONCLUSION Our study suggests that cryotherapy as well as cryocompression is a safe and effective way to cool patients' extremities to lower the prevalence of CIPN. Cryocompression was not more effective than cryotherapy alone in the prevention of CIPN.
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Affiliation(s)
- Christine Brunner
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria.
| | - Miriam Emmelheinz
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
| | - Daniel Egle
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
| | - Magdalena Ritter
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
| | - Katharina Leitner
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
| | - Verena Wieser
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
| | - Carmen Albertini
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
| | - Samira Abdel Azim
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
| | - Irene Mutz-Dehbalaie
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
| | - Johanna Kögl
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
| | - Christian Marth
- Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
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10
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Wu H, Jin Y, Song J, Gao X. Effect of frozen gloves on chemotherapy-induced neurotoxicity in breast cancer patients: a systematic review and meta-analysis. Front Oncol 2024; 14:1366782. [PMID: 38903710 PMCID: PMC11187580 DOI: 10.3389/fonc.2024.1366782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Accepted: 05/01/2024] [Indexed: 06/22/2024] Open
Abstract
Background Chemotherapy-induced peripheral neurotoxicity (CIPN) is a dose-limiting side effect observed in breast cancer patients. Its primary clinical manifestations include limb numbness, tingling sensations, hypoesthesia, or paresthesia. In severe instances, some patients may also encounter muscle cramps, weakness, and pain, leading to potential paralysis. The onset of CIPN significantly impacts the quality of life for cancer patients. Hence, it is imperative to explore preventive strategies for managing CIPN. Methods We searched for relevant randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) in several databases. The primary outcome measures encompassed the Patient Neurotoxicity Questionnaire (PNQ), the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Secondary outcomes aimed to evaluate the quality of life and the tolerability of ice gloves. Meta-analysis was conducted using RevMan 5.3 software to determine the relative risk ratio (RR) and 95% confidence interval (CI). Results We conducted an analysis involving 372 patients across seven trials. In our meta-analysis, the use of ice gloves demonstrated non-significant results in reducing the incidence of both motor and sensory neuropathy, as assessed through CTCAE (sensory: RR: 0.94; 95% CI: 0.85 to 1.02; P = 0.15; motor: RR: 1.04; 95% CI: 0.88 to 1.22; P = 0.64). Similarly, when evaluated using the PNQ, there was no significant reduction observed in the incidence of sensory and motor neuropathy (sensory: RR: 0.49; 95% CI: 0.20 to 1.20; P = 0.12; motor: RR: 0.71; 95% CI: 0.26 to 1.99; P = 0.52). Consistently, our conclusions remained unchanged when employing the FACT-Taxane assessment. Regarding the evaluation of the quality of life, our observations suggested a potential improvement with the use of ice gloves, and participants exhibited moderate tolerance towards them. Conclusion Ice gloves are a reasonable option for the treatment of CIPN in patients undergoing chemotherapy for breast cancer. However, the effectiveness of ice gloves in combating CIPN remains inconclusive at this time due to the low quality and limited number of clinical trials on this topic. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023457045, identifier CRD42023457045.
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Affiliation(s)
- Hongting Wu
- First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Ying Jin
- First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jiaqing Song
- First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xiufei Gao
- First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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11
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Dongxue G, Fangfei Z, Ran L, Lizhi Z. Effect of gradient pressure therapy on the prevention of chemotherapy-induced peripheral neuropathy in patients with breast cancer. Support Care Cancer 2024; 32:367. [PMID: 38761270 DOI: 10.1007/s00520-024-08581-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 05/14/2024] [Indexed: 05/20/2024]
Abstract
PURPOSE To investigate the effect of gradient pressure therapy on the prevention of chemotherapy-induced peripheral neuropathy (CIPN) and improvement in activities of daily living (ADL) in patients with breast cancer. METHODS Eighty female patients with breast cancer treated at Tangshan People's Hospital between October 2022 and July 2023 were selected as research participants and divided into control and intervention, with 40 patients in each group. The control group received routine treatment and care, whereas the intervention group received gradient pressure therapy based on routine treatment and care. Incidence of peripheral neuropathy and the degree of impact on ADL between the two groups were compared after the intervention for cycles 2, 4, and 6. RESULTS There was no significant difference in the general information between the two groups (P > 0.05). After two intervention cycles, there was no significant difference in the incidence of CIPN, various dimensions of Chemotherapy-Induced Peripheral Neuropathy Assessment Tool (CIPNAT), and total scores between the two groups (P > 0.05). After four intervention cycles, the two groups had a statistically significant difference in the incidence of CIPN, sensory dimension, general activity dimension, and total CIPNAT score (P < 0.05). After six intervention cycles, there was a significant difference in the incidence of CIPN, sensory dimension, fine activity dimension, general activity dimension, and total CIPNAT score between the two groups (P < 0.05), while there was no significant difference in the other dimensions (P > 0.05). CONCLUSIONS Gradient pressure therapy can effectively prevent or alleviate peripheral neuropathy in patients with breast cancer undergoing chemotherapy and improve their ability to perform ADL. Thus, it is safe, effective, and worthy of clinical application. TRIAL REGISTRATION RMYY-LLKS-2022-054.
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Affiliation(s)
- Guo Dongxue
- North China University of Science and Technology, Tangshan, 063210, China
| | - Zhao Fangfei
- North China University of Science and Technology Affiliated Hospital, Tangshan, 063000, China
| | - Li Ran
- North China University of Science and Technology, Tangshan, 063210, China
| | - Zhou Lizhi
- Tangshan People's Hospital, Tangshan, 063000, China.
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12
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Okazaki M, Bando H, Terasaki A, Ueda A, Iguchi-Manaka A, Mathis BJ, Hara H. Safety and Efficacy of Compression Therapy to Prevent Chemotherapy-Induced Peripheral Neuropathy in Lower Extremities of Breast Cancer Patients: A Pilot Study. Cureus 2024; 16:e60998. [PMID: 38910688 PMCID: PMC11193973 DOI: 10.7759/cureus.60998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/24/2024] [Indexed: 06/25/2024] Open
Abstract
Background Chemotherapy-induced peripheral neuropathy (CIPN) is a problematic adverse event for breast cancer patients receiving taxane antimitotic agents. We evaluated the effectiveness of compression therapy against CIPN in the lower extremities of breast cancer patients receiving taxanes. Methods Eligible patients scheduled for perioperative treatment with taxanes for early-stage breast cancer were enrolled. Each patient wore latex-free surgical gloves and compression socks, putting on two layers of each 15 minutes before the administration of taxanes and removing them 15 minutes after administration. Peripheral neuropathy (PN) was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and the Patient Neurotoxicity Questionnaire (PNQ). The primary endpoint was the incidence of CTCAE version 4.0 grade 2 or higher CIPN in the lower extremities during the entire period of perioperative chemotherapy with taxanes. Results PN assessment by CTCAE in the lower extremities, the primary outcome, showed that 13.3% developed grade 2 sensory disturbances, and 8.3% developed grade 2 motor disturbances. The incidence of CTCAE grade 2 or higher PN in the hands was 26.7% for sensory disturbances and 13.3% for motor disturbances during the entire study period. No patient had grade 3 or higher PN. No adverse events due to compression therapy were observed. Conclusion Compression of the lower extremities with compression socks tended to reduce the incidence of CIPN compared to the general incidence. Compression therapy may help prevent the development of CIPN.
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Affiliation(s)
- Mai Okazaki
- Department of Breast and Endocrine Surgery, University of Tsukuba Hospital, Tsukuba, JPN
| | - Hiroko Bando
- Department of Breast and Endocrine Surgery, University of Tsukuba Hospital, Tsukuba, JPN
| | - Azusa Terasaki
- Department of Breast and Endocrine Surgery, University of Tsukuba Hospital, Tsukuba, JPN
| | - Aya Ueda
- Department of Breast and Endocrine Surgery, University of Tsukuba Hospital, Tsukuba, JPN
| | - Akiko Iguchi-Manaka
- Department of Breast and Endocrine Surgery, University of Tsukuba Hospital, Tsukuba, JPN
| | - Bryan J Mathis
- Department of Cardiology, International Medical Center, University of Tsukuba Hospital, Tsukuba, JPN
| | - Hisato Hara
- Department of Breast and Endocrine Surgery, University of Tsukuba Hospital, Tsukuba, JPN
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13
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Tandon M, Yacur M, Brenin C, Dillon P. Cryotherapy for prevention of chemotherapy induced peripheral neuropathy in breast cancer. Crit Rev Oncol Hematol 2024; 194:104244. [PMID: 38135017 DOI: 10.1016/j.critrevonc.2023.104244] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 09/11/2023] [Accepted: 12/18/2023] [Indexed: 12/24/2023] Open
Abstract
Peripheral neuropathy is a well-described complication of chemotherapy. There are no known treatments to reverse peripheral neuropathy. Chemotherapy-induced peripheral neuropathy is a dose-limiting toxicity in cancer treatment and is debilitating. Cryotherapy, or the use of cold garments/ice bags applied to extremities during chemotherapy, is a method to prevent or minimize treatment related neuropathy. There is no standard method of providing cryotherapy currently. A review of the literature was performed revealing that a variety of cryotherapy methods exist. While small studies suggest potential preventive effect of some forms of cryotherapy, consistent results from well-designed randomized studies are lacking. A small benefit from the use of cryotherapy to prevent peripheral neuropathy might exist, but conflicting studies exist. In light of the low cost to implement ice bags during chemotherapy and the low risk of toxicity, the use of ice bags may be reasonable during taxane chemotherapy for the treatment of breast cancer.
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Affiliation(s)
- Mihir Tandon
- University of Virginia, Department of Medicine, Charlottesville, VA 22908, USA
| | - Melissa Yacur
- Inova-Schar Cancer Institute, Department of Medical Oncology, Fairfax, VA 22031, USA
| | - Christiana Brenin
- University of Virginia, Department of Medicine, Charlottesville, VA 22908, USA
| | - Patrick Dillon
- University of Virginia, Department of Medicine, Charlottesville, VA 22908, USA.
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14
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Accordino MK, Lee S, Leu CS, Levin B, Trivedi MS, Crew KD, Kalinsky K, Raghunathan R, Faheem K, Harden E, Taboada A, de Oliveira BD, Larson E, Franks L, Honan E, Law C, Hershman DL. Randomized adaptive selection trial of cryotherapy, compression therapy, and placebo to prevent taxane-induced peripheral neuropathy in patients with breast cancer. Breast Cancer Res Treat 2024; 204:49-59. [PMID: 38060077 PMCID: PMC10840989 DOI: 10.1007/s10549-023-07172-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 11/02/2023] [Indexed: 12/08/2023]
Abstract
BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of taxane therapy. Small non-randomized studies in patients with early-stage breast cancer (ESBC) suggest both cryotherapy and compression therapy may prevent CIPN. It is unknown which is more effective. METHODS We conducted a randomized phase IIB adaptive sequential selection trial of cryotherapy vs. compression therapy vs. placebo ("loose" gloves/socks) during taxane chemotherapy. Participants were randomized in triplets. Garments were worn for 90-120 min, beginning 15 min prior and continuing for 15 min following the infusion. The primary goal was to select the best intervention based on a Levin-Robbins-Leu sequential selection procedure. The primary endpoint was a < 5-point decrease in the Functional Assessment of Cancer Therapy Neurotoxicity (FACT-NTX) at 12 weeks. An arm was eliminated if it had four or more fewer successes than the currently leading arm. Secondary endpoints included intervention adherence and patient-reported comfort/satisfaction. RESULTS Between April 2019 and April 2021, 63 patients were randomized (cryotherapy (20); compression (22); placebo (21)). Most patients (60.3%) were treated with docetaxel. The stopping criterion was met after the 17th triplet (n = 51) was evaluated; success at 12 weeks occurred in 11 (64.7%) on compression therapy, 7 (41.1%) on cryotherapy, and 7 (41.1%) on placebo. Adherence to the intervention was lowest with cryotherapy (35.0%) compared to compression (72.7%) and placebo (76.2%). CONCLUSION Compression therapy was the most effective intervention in this phase IIB selection trial to prevent CIPN and was well tolerated. Compression therapy for the prevention of CIPN should be evaluated in a phase III study. CLINICAL TRIAL REGISTRATION ClinicaTrials.gov Identifier: NCT03873272.
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Affiliation(s)
- Melissa K Accordino
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA.
| | - Shing Lee
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA
- Department of Biostatistics, Columbia University Medical Center, New York, NY, USA
| | - Cheng Shiun Leu
- Department of Biostatistics, Columbia University Medical Center, New York, NY, USA
| | - Bruce Levin
- Department of Biostatistics, Columbia University Medical Center, New York, NY, USA
| | - Meghna S Trivedi
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA
| | - Katherine D Crew
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA
| | - Kevin Kalinsky
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Rohit Raghunathan
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA
- Department of Biostatistics, Columbia University Medical Center, New York, NY, USA
| | - Khadija Faheem
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA
| | - Erik Harden
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA
| | - Alessandra Taboada
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA
| | | | - Elisabeth Larson
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA
| | - Lauren Franks
- Department of Biostatistics, Columbia University Medical Center, New York, NY, USA
| | - Erin Honan
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA
| | - Cynthia Law
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA
| | - Dawn L Hershman
- Division of Hematology/Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, 161 Ft Washington Ave #1071, New York, NY, 212-305-1945, USA
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15
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Anastasio MK, Unnithan S, Scott A, Hayes T, Shah S, Moss HA, Erkanli A, Havrilesky LJ. Cryocompression to Reduce Peripheral Neuropathy in Gynecologic Cancer: A Randomized Controlled Trial. Obstet Gynecol 2023; 142:1459-1467. [PMID: 37883997 DOI: 10.1097/aog.0000000000005419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 08/24/2023] [Indexed: 10/28/2023]
Abstract
OBJECTIVE To investigate the efficacy of cryocompression therapy to prevent chemotherapy-induced peripheral neuropathy. METHODS This single-institution, randomized, self-controlled trial of cryocompression enrolled gynecologic cancer patients planned for five to six cycles neurotoxic chemotherapy. Exclusion criteria were prior neurotoxic chemotherapy or baseline peripheral neuropathy. Participants were randomized to cryocompression on dominant versus non-dominant hand and foot (treatment), with no intervention on the opposite side (control). Compression socks and gloves and ice bags were applied 15 minutes before, during, and 15 minutes after infusion. Primary outcome measures included the PNQ (Patient Neurotoxicity Questionnaire) and the Semmes-Weinstein monofilament test; secondary outcomes included the FACT/GOG-NTX (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity) and patient acceptability and tolerability. Sixty patients completing the study were necessary to detect a 70% reduction in the odds of PNQ grade C or higher peripheral sensory neuropathy with 80% power. RESULTS Ninety-one patients were enrolled from January 2021 to October 2022; 69 were eligible for final analysis. Of the 91 patients, 64.8% were White, 30.8% were Black, and 1.1% were Hispanic or Latina. With successive cycles, more patients had sensory PNQ grade C or higher neuropathy on the control side compared with the cryocompression side. Cryocompression decreased the odds of sensory neuropathy (PNQ grade C or higher) by 46% at final visit (odds ratio 0.54, 95% CI 0.31-0.94; P =.03). There was no difference in tactile sensitivity based on the monofilament test between sides at the final visit. At the final visit, average FACT/GOG-NTX-11 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 11 Item Version) scores were significantly lower on the cryocompression than the control side (estimate -0.97, 95% CI -1.89 to -0.06; P =.04), as were FACT/GOG-NTX-4 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 4 Item Version) scores (estimate -0.35, 95% CI -0.64 to -0.05; P =.02). More than 85% of patients assessed the intervention as acceptable and tolerable. CONCLUSIONS Cryocompression therapy reduces subjective chemotherapy-induced peripheral sensory neuropathy in patients who are receiving paclitaxel or cisplatin for gynecologic cancer. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov , NCT04563130.
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Affiliation(s)
- Mary Katherine Anastasio
- Department of Obstetrics and Gynecology, the Department of Biostatistics and Bioinformatics, the Department of Neurology, and the Duke Cancer Institute, Duke University Medical Center, and the Division of Gynecologic Oncology, Duke Cancer Institute, Durham, North Carolina
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16
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Fu Z, Gao C, Wu T, Wang L, Li S, Zhang Y, Shi C. Peripheral neuropathy associated with monomethyl auristatin E-based antibody-drug conjugates. iScience 2023; 26:107778. [PMID: 37727735 PMCID: PMC10505985 DOI: 10.1016/j.isci.2023.107778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/21/2023] Open
Abstract
Since the successful approval of gemtuzumab ozogamicin, antibody-drug conjugates (ADCs) have emerged as a pivotal category of targeted therapies for cancer. Among these ADCs, the use of monomethyl auristatin E (MMAE) as a payload is prevalent in the development of ADC drugs, which has significantly improved overall therapeutic efficacy against various malignancies. However, increasing clinical observations have raised concerns regarding the potential nervous system toxicity associated with MMAE-based ADCs. Specifically, a higher incidence of peripheral neuropathy has been reported in ADCs incorporating MMAE as payloads. Considering the increasing global use of MMAE-based ADCs, it is imperative to provide an inclusive overview of diagnostic and management strategies for this adverse event. In this review, we examine current information and what future research directions are required to better understand and manage this type of clinical challenge.
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Affiliation(s)
- Zhiwen Fu
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430000, China
| | - Chen Gao
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430000, China
| | - Tingting Wu
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430000, China
| | - Lulu Wang
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430000, China
| | - Shijun Li
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430000, China
| | - Yu Zhang
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430000, China
| | - Chen Shi
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China
- Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430000, China
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17
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Lustberg MB, Kuderer NM, Desai A, Bergerot C, Lyman GH. Mitigating long-term and delayed adverse events associated with cancer treatment: implications for survivorship. Nat Rev Clin Oncol 2023; 20:527-542. [PMID: 37231127 PMCID: PMC10211308 DOI: 10.1038/s41571-023-00776-9] [Citation(s) in RCA: 88] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/26/2023] [Indexed: 05/27/2023]
Abstract
Despite the importance of chemotherapy-associated adverse events in oncology practice and the broad range of interventions available to mitigate them, limited systematic efforts have been made to identify, critically appraise and summarize the totality of evidence on the effectiveness of these interventions. Herein, we review the most common long-term (continued beyond treatment) and late or delayed (following treatment) adverse events associated with chemotherapy and other anticancer treatments that pose major threats in terms of survival, quality of life and continuation of optimal therapy. These adverse effects often emerge during and continue beyond the course of therapy or arise among survivors in the months and years following treatment. For each of these adverse effects, we discuss and critically evaluate their underlying biological mechanisms, the most commonly used pharmacological and non-pharmacological treatment strategies, and evidence-based clinical practice guidelines for their appropriate management. Furthermore, we discuss risk factors and validated risk-assessment tools for identifying patients most likely to be harmed by chemotherapy and potentially benefit from effective interventions. Finally, we highlight promising emerging supportive-care opportunities for the ever-increasing number of cancer survivors at continuing risk of adverse treatment effects.
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Affiliation(s)
- Maryam B Lustberg
- Department of Medicine, Yale University School of Medicine, New Haven, CT, USA
| | | | - Aakash Desai
- Department of Medicine, Mayo Clinic School of Medicine, Rochester, MN, USA
| | - Cristiane Bergerot
- Centro de Câncer de Brasília, Instituto Unity de Ensino e Pesquisa, Brasilia, Brazil
| | - Gary H Lyman
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
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18
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Machida R, Sakamaki K, Kuchiba A. Clinical trial design and analysis for comparing three treatments with intra-individual right- and left-hand data. Clin Trials 2023; 20:203-210. [PMID: 36651336 DOI: 10.1177/17407745221150281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Chemotherapy-induced peripheral neuropathy can occur in the right and left hand. Studies on prevention treatments for chemotherapy-induced peripheral neuropathy have largely adopted either self-controlled designs or parallel designs to compare two preventive treatments. When three treatment options (two experimental treatments and a control treatment) are available, both designs can be extended. However, no clinical trials have adopted a self-controlled design to compare three prevention treatments for chemotherapy-induced peripheral neuropathy. The incomplete block crossover design for more than two treatments can be extended to compare three treatments in the self-controlled design. In simple extension, some of the participants receive two experimental treatments in both hands; however, it may be difficult to administer different experimental treatments in both hands for practical reasons, such as a concern for the different types of unexpected adverse events. This study proposes a design and analysis method appropriate for the situation where only one experimental treatment is provided to each participant. METHODS We assume clinical trials to compare each of the two experimental treatments (E1 and E2) with the control treatment (C) and between two experimental treatments only when both experimental treatments are superior to the control treatment. We propose a self-controlled design, which equally randomizes to four arms to adjust for the dominant hand effect: Arm 1: E1 for right hand, C for left hand; Arm 2: C for right hand, E1 for left hand; Arm 3: E2 for right hand, C for left hand; and Arm 4: C for right hand, E2 for left hand. We compare operating characteristics of the proposed design with the three-arm parallel design in which the same treatment is performed in both hands by participants. We also assess three proposed analysis methods for comparisons between experimental treatments in the self-controlled design under several conditions of correlations between right and left hands using simulation studies. RESULTS The simulation studies showed that the proposed design was more powerful than the three-arm parallel design when correlation was 0.3 or higher. For comparisons between experimental treatments, the methods based on the regression model, including the outcome of hands with C as a covariate, had the highest power under modest to high correlation among the analysis methods in the self-controlled design. CONCLUSION The proposed design can improve the power for comparing between two experimental treatments and the control treatment. Our design is useful in situations where it is undesirable for participants to receive different experimental treatments in both hands for practical reasons.
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Affiliation(s)
- Ryunosuke Machida
- Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Tokyo, Japan
| | - Kentaro Sakamaki
- Center for Data Science, Yokohama City University, Yokohama, Japan
| | - Aya Kuchiba
- Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Tokyo, Japan
- Graduate School of Health Innovation, Kanagawa University of Human Services, Kanagawa, Japan
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Kanda K, Ishida K, Kyota A, Ishihara C, Fujimoto K, Hosokawa M, Mochizuki R. Randomized clinical trial quantifying the effectiveness of a self-monitoring intervention in cancer patients with peripheral neuropathy: A quantitative study. Asia Pac J Oncol Nurs 2023; 10:100198. [PMID: 36949819 PMCID: PMC10025959 DOI: 10.1016/j.apjon.2023.100198] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 01/27/2023] [Indexed: 02/05/2023] Open
Abstract
Objective The aim of this study was to quantitatively evaluate the efficacy of a self-monitoring intervention for the management of persistent chemotherapy-induced peripheral neuropathy (CIPN). Methods A randomized controlled clinical trial was conducted on 65 outpatients receiving taxane or platinum-based anticancer drugs. Participants were assigned to the control group (CG; n = 32) or the self-monitoring group (SMG; n = 33) and followed for 6 weeks. Non-interveners were blinded. Participants in the intervention group self-monitored and recorded. The researchers provided feedback on the recorded symptoms and coping strategies once every 3 weeks. The efficacy of the 6-week self-monitoring intervention was assessed, using various measures, at baseline (T0), 3 weeks (T1), and 6 weeks (T2). Scores of CIPN, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, Distress and Impact Thermometer, Self-Efficacy Scale for Advanced Cancer, and Functional Assessment of Cancer Therapy-General of both groups were compared. Safety behavior in daily life was also compared. The study was conducted from August 9, 2017 to March 30, 2020 in outpatient clinics at three hospitals. Analysis was conducted using the t-test, Mann-Whitney U test, χ2 test, and two-way repeated-measures analysis of variance (two-way RMANOVA). Results No significant differences were noted between the two groups in the CIPN score, the Distress and Impact Thermometer score, and in safety behavior in daily life. The mean Self-Efficacy Scale for Advanced Cancer score at T1 differed between the two groups (CG mean ± SD: 358.44 ± 109.90; SMG mean ± SD: 421.21 ± 85.54), which was significantly higher in the SMG (P = 0.012). Two-way RMANOVA revealed an interaction between the CG and SMG (F = 5.689, P = 0.004). Quality of life scores were higher in the SMG than in the CG at T0, T1, and T2. Two-way RMANOVA analysis showed an effect of the intervention (F = 7.914, P = 0.007). Conclusions The self-monitoring intervention maintained the participants' quality of life. This finding suggests its effectiveness in patients with peripheral neuropathy.
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Affiliation(s)
- Kiyoko Kanda
- Nursing Department, Takasaki University of Health and Welfare, Takasaki-shi, Japan
- Corresponding author.
| | | | - Ayumi Kyota
- Gunma University, Graduate School of Health Sciences, Maebashi-shi, Japan
| | | | - Keiko Fujimoto
- Nursing Department, Takasaki University of Health and Welfare, Takasaki-shi, Japan
| | - Mai Hosokawa
- Iwate Prefectural University, Faculty of Nursing/Graduate School of Nursing, Takizawa, Japan
| | - Ruka Mochizuki
- Jikei University School of Medicine, School of Nursing, Chouhu-shi, Japan
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Casanovas-Marsal JO, Morales Hijazo L, Grima Campos L, Calvo Sanz V, Fernández Castro B, González de la Cuesta D. [Peripheral neuropathy, onycholysis and health-related quality of life in womens with breast cancer treated with taxanes. Prospective longitudinal study.]. Rev Esp Salud Publica 2023; 97:e202302008. [PMID: 36755503 PMCID: PMC10558105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 01/19/2023] [Indexed: 02/10/2023] Open
Abstract
OBJECTIVE Peripheral neuropathy and onycholysis are adverse events produced by taxanes in breast cancer that persist even after the end of treatment and negatively influence quality of life. The objectives of the study were to describe these side effects and the degree of involvement and relating them to the drug doses received. METHODS Prospective, cross-sectional study of in 50 womens dignosed of breast cancer, treated with docetaxel and paclitaxel in Hospital Universitario Miguel Servet in Zaragoza (Aragón, Spain). CTCAE v.5.0 scale and Semes Weinsten test were used to evaluate peripheral neuropathy and onycholysis. ECOG scale was performed to measure the health-related quality of life. Study variables were evaluated before-during treatment and 1 and 6 months after finish treatment. Statistical analysis was performed using Jamovi 1.2®. For the relationship of the qualitative variables, the chi-square, Fisher's exact test, Mc's test were used. Nemar and the Odds Ratio test. Effects were considered significant if p<0.05. RESULTS 43 subjects were included. During treatment the 9.8 presented motor neuropathy and 12.2% sensitive neuropathy, 37.2% onycholisis in upper extremities and 39.5% in lower extremities (χ2=11.3; p<0.001 / χ2=13.0; p<0.001) and 38.1% a health related quality of live limited in excessive activities (χ2=10.3; p=0.001). Post-treatment evaluation the 20.9% presented motor neuropathy and 32.6% sensitive neuropathy (χ2=3.57; p=0.059 / χ2=6.23; p=0.013), the 86% onycholisis in upper extremities and lower extremities (χ2=6.07; p=0.048 / χ2=10.1; p=0.006) and 58.5% a health related quality of live limited in excessive activities (χ2=8.47; p=0.014). 6 month later, the initials parameters were not recuperated. CONCLUSIONS Taxanes have a negative impact on the health-related quality of life in patients, even 6 months after finishing treatment due to the peripheral neuropathy and onycholysis that they cause.
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Affiliation(s)
| | - Lorena Morales Hijazo
- Enfermera, Hospital de Día de Oncología, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón. Zaragoza. España
| | - Laura Grima Campos
- Enfermera, Hospital de Día de Oncología, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón. Zaragoza. España
| | - Vanesa Calvo Sanz
- Enfermera, Hospital de Día de Oncología, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón. Zaragoza. España
| | - Belén Fernández Castro
- Enfermera, Supervisora Hospital de Día de Oncología, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón. Zaragoza. España
| | - Delia González de la Cuesta
- Enfermera, Supervisora de área investigación e innovación, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón. Zaragoza. España
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21
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Chai Y, Zhao F, Ye P, Ma F, Wang J, Zhang P, Li Q, Wang J, Wang W, Li Q, Xu B. A Prospective, Randomized, Placebo-Controlled Study Assessing the Efficacy of Chinese Herbal Medicine (Huangqi Guizhi Wuwu Decoction) in the Treatment of Albumin-Bound Paclitaxel-Induced Peripheral Neuropathy. J Clin Med 2023; 12:jcm12020505. [PMID: 36675434 PMCID: PMC9863646 DOI: 10.3390/jcm12020505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 01/02/2023] [Accepted: 01/03/2023] [Indexed: 01/11/2023] Open
Abstract
Objective: This study aimed to evaluate the efficacy and safety of Huangqi Guizhi Wuwu decoction (HGWD), which is composed of five crude drugs (Astragali Radix, Cinnamomi Ramulus, Paeoniae Radix Alba, Zingiberis Rhizoma Recens, and Jujubae Fructus), in the treatment of albumin-bound paclitaxel (nab-PTX)-induced peripheral neuropathy (PN) in Chinese patients with breast cancer (BC). Methods: This trial was conducted at the National Cancer Center in China from January 2020 to June 2022. The eligible participants were assigned randomly in a 1:1 ratio to an HGWD group or a control group. The outcome measure was EORTC QLQ-CIPN20 questionnaire. Results: 92 patients diagnosed with BC were enrolled and randomized to either HGWD group (n = 46) or control group (n = 46). There were no significant differences in baseline characteristics between the two groups (p > 0.05). A statistical analysis of the sensory and motor functions of the EORTC QLQ-CIPN20 scores showed that patients in the HGWD group reported a larger decrease in CIPN sensory scores than those in the control group (p < 0.001). The EORTC QLQ-CIPN20 autonomic scores showed no statistical significance between the two groups (p > 0.05). Conclusions: HGWD packs could significantly improve patients’ nab-PTX-induced PN, increase the tolerance for nab-PTX-containing chemotherapy, and further improve the quality of life of patients with BC.
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Affiliation(s)
- Yue Chai
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Fang Zhao
- Nursing Department of the Cancer Hospital, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Peizhi Ye
- Chinese Medicine Department of the Cancer Hospital, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Fei Ma
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jiayu Wang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Pin Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Qing Li
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jiani Wang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wenna Wang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Qiao Li
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Correspondence: (Q.L.); (B.X.)
| | - Binghe Xu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Correspondence: (Q.L.); (B.X.)
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22
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Chan A, Elsayed A, Ng DQ, Ruddy K, Loprinzi C, Lustberg M. A global survey on the utilization of cryotherapy and compression therapy for the prevention of chemotherapy-induced peripheral neuropathy. Support Care Cancer 2022; 30:10001-10007. [PMID: 36214880 PMCID: PMC9715474 DOI: 10.1007/s00520-022-07383-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 10/01/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect that is highly prevalent among cancer patients undergoing chemotherapy. There is a growing use of cryotherapy (CryTx) and compression therapy (ComTx) to prevent CIPN at cancer centers worldwide. In this study, we examined the awareness and recommendation of these modalities and evaluated factors associated with awareness. In addition, we investigated the type of technology utilized, barriers to implementation, and perceived adverse events of CryTx and ComTx. METHODS Active members of the Multinational Association of Supportive Care of Cancer (MASCC) were invited to complete an electronic survey that was sent via SurveyMonkey between September and October 2021. The survey assessed participants' awareness, recommendation, usage, barriers to utilization, and perceived adverse events of CryTx and ComTx. Descriptive statistics and multiple logistic regression were utilized to analyze findings. RESULTS Out of 184 participants, 70.1% were physicians, 73.4% had over 10 years of practice, and 49.5% were practicing in an outpatient setting. While more than half (63.3%) of participants indicated awareness of CryTx for taxane-induced peripheral neuropathy, less than a quarter (22.8%) indicated recommendation in their practice setting. Factors associated with higher awareness of CryTx for patients receiving taxanes include living in Europe (OR = 2.69, 95% CI [1.28-5.64], p = 0.009), not practicing in an inpatient setting (OR = 3.15, 95% CI [1.45-6.85], p = 0.004), and self-identifying as non-physician (OR = 2.40, 95% CI [1.03-4.37], p = 0.041). Commercial cooling (31.5%) and compression (16.8%) gloves and socks were the most used modalities for CryTx and ComTx, respectively. The most identified barriers to CryTx and ComTx utilization include insufficient evidence (53.5%), logistics (34.8%), and patient discomfort (23.4%). Redness/irritation of skin (27.7%) and numbness/tingling (24.5%) accounted for about half of the perceived adverse events associated with use of CryTx and ComTx. CONCLUSION Results of our global survey illustrated that there are varying modes in the delivery of CryTx and ComTx among cancer centers around the world. Education of the utilization of CryTx and ComTx, in addition to efficacy and implementation studies, is needed to close the gap between awareness and implementation in clinical practice.
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Affiliation(s)
- Alexandre Chan
- Department of Clinical Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USA.
- Department of Pharmacy, University of California Irvine Health, Irvine, CA, USA.
| | - Amna Elsayed
- Department of Pharmacy, University of California Irvine Health, Irvine, CA, USA
| | - Ding Quan Ng
- Department of Clinical Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USA
| | - Kathryn Ruddy
- Department of Oncology, Mayo Clinic Alix School of Medicine, Rochester, MN, USA
| | - Charles Loprinzi
- Department of Oncology, Mayo Clinic Alix School of Medicine, Rochester, MN, USA
| | - Maryam Lustberg
- Breast Medical Oncology, Yale Cancer Center, New Haven, CT, USA
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23
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Kanbayashi Y, Sakaguchi K, Ishikawa T, Tabuchi Y, Takagi R, Yokota I, Katoh N, Takayama K, Taguchi T. Predictors of the development of nab-paclitaxel-induced peripheral neuropathy in breast cancer patients: post hoc analysis of a prospective, phase II, self-controlled clinical trial. MEDICAL ONCOLOGY (NORTHWOOD, LONDON, ENGLAND) 2022; 39:153. [PMID: 35852641 DOI: 10.1007/s12032-022-01754-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/17/2022] [Indexed: 02/07/2023]
Abstract
In a previous study, we showed that cryotherapy and compression therapy have comparable efficacy in preventing nab-paclitaxel-induced peripheral neuropathy. However, even with cryotherapy or compression therapy, there were patients with National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade ≥ 2 and/or Patient Neurotoxicity Questionnaire (PNQ) grade ≥ D peripheral neuropathies. Therefore, this post hoc analysis was performed to identify predictors of nab-paclitaxel-induced peripheral neuropathy. The clinical data in this post hoc analysis were the data of 38 breast cancer patients receiving chemotherapy with nanoparticle albumin-bound paclitaxel (nab-PTX) at our outpatient chemotherapy center from August 2017 to March 2019. The number of patients was analyzed assuming that there were data for 76 hands. Variables related to the development of nab-PTX-induced peripheral neuropathy were used for regression analysis. Multivariate-ordered logistic regression analysis was performed to identify predictors for the development of nab-PTX-induced peripheral neuropathy. Significant factors included smoking history [odds ratio (OR) 4.64, 95% confidence interval (CI) 1.60-13.5; P = 0.0048] with neuropathy evaluated by CTCAE, body mass index (BMI) (OR 1.13, 95% CI 1.01-1.26; P = 0.039) with neuropathy evaluated by PNQ (sensory), and smoking history (OR 3.80, 95% CI 1.40-10.30; P = 0.0087) and age (OR 1.06, 95% CI 1.01-1.11; P = 0.012) with neuropathy evaluated by PNQ (motor). In conclusion, smoking history, BMI and age were identified as significant predictors of the development of nab-PTX-induced-peripheral neuropathy.
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Affiliation(s)
- Yuko Kanbayashi
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan.
- Department of Endocrine and Breast Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
- Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
| | - Koichi Sakaguchi
- Department of Endocrine and Breast Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takeshi Ishikawa
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yusuke Tabuchi
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Pharmacy, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Ryo Takagi
- Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Hokkaido, Japan
| | - Isao Yokota
- Department of Biostatistics, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Norito Katoh
- Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Koichi Takayama
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tetsuya Taguchi
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Endocrine and Breast Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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24
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Nicolae R, Uccellini A, Siderov J, Mellerick A, Wong V, Yeo B. Taxane-induced neuropathy: How serious is this problem for patients with early breast cancer? Asia Pac J Clin Oncol 2022; 19:e118-e127. [PMID: 35692105 DOI: 10.1111/ajco.13804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 03/30/2022] [Accepted: 05/09/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Taxanes form the mainstay of breast cancer therapy in the curative setting. Taxane-induced peripheral neuropathy (TIPN) is a common toxicity and confers significant morbidity with no validated therapies. Literature detailing TIPN is inconsistent in reporting its frequency, severity, risk factors, impact upon treatment course, and management practices. METHODS A retrospective chart review was performed including 348 early-stage breast cancer patients undergoing weekly paclitaxel therapy between 2010 and 2020 in the adjuvant or neoadjuvant setting. The frequency, severity, and impact on treatment from TIPN were analyzed during treatment and at one year follow-up. Clinicopathological and patient factors were collected to identify potential risk factors. RESULTS 279 out of 348 patients (80.2%) developed TIPN of any grade. One-year follow-up was available for 232 of the original 279 TIPN patients (83.2%). Of these, 52 patients (22.4%) exhibited persisting TIPN of any grade. The presence and severity of TIPN during treatment was significantly associated with a lower median dose intensity (100% versus 82.5% for non-TIPN and all-grade TIPN respectively, p < 0.001). Neoadjuvant treatment (p = 0.038) and body surface area (BSA, p = 0.035) were independently associated with TIPN during treatment. Increased age (p < .001) and pre-treatment diabetes (p = 0.009) were associated with TIPN at one-year follow-up. CONCLUSION TIPN is common in breast cancer patients undergoing weekly paclitaxel therapy. TIPN results in patients receiving significantly lower dose intensity due to dose reductions and premature treatment cessation. Future prospective studies in similar cohorts are warranted, with a focus on long-term outcomes.
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Affiliation(s)
- Robert Nicolae
- Austin Health, Olivia Newton-John Cancer Wellness and Research Centre Melbourne, Melbourne, Australia
| | - Anthony Uccellini
- Austin Health, Olivia Newton-John Cancer Wellness and Research Centre Melbourne, Melbourne, Australia
| | - Jim Siderov
- Austin Health, Olivia Newton-John Cancer Wellness and Research Centre Melbourne, Melbourne, Australia
| | - Angela Mellerick
- Austin Health, Olivia Newton-John Cancer Wellness and Research Centre Melbourne, Melbourne, Australia
| | - Vanessa Wong
- Austin Health, Olivia Newton-John Cancer Wellness and Research Centre Melbourne, Melbourne, Australia
| | - Belinda Yeo
- Austin Health, Olivia Newton-John Cancer Wellness and Research Centre Melbourne, Melbourne, Australia
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25
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Tamburin S, Park SB, Schenone A, Mantovani E, Hamedani M, Alberti P, Yildiz-Kabak V, Kleckner IR, Kolb N, Mazzucchelli M, McNeish BL, Argyriou AA, Cavaletti G, Hoke A. Rehabilitation, exercise, and related non-pharmacological interventions for chemotherapy-induced peripheral neurotoxicity: Systematic review and evidence-based recommendations. Crit Rev Oncol Hematol 2022; 171:103575. [PMID: 34968623 PMCID: PMC10658987 DOI: 10.1016/j.critrevonc.2021.103575] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/23/2021] [Accepted: 12/24/2021] [Indexed: 12/22/2022] Open
Abstract
Pharmacological strategies for chemotherapy-induced peripheral neurotoxicity (CIPN) are very limited. We systematically reviewed data on rehabilitation, exercise, physical therapy, and other physical non-pharmacological interventions and offered evidence-based recommendations for the prevention and treatment of CIPN. A literature search using PubMed, Web of Science and CINAHL was conducted from database inception until May 31st, 2021. 2791 records were title-abstract screened, 71 papers were full-text screened, 41 studies were included, 21 on prevention and 20 on treatment of CIPN. Treatment type, cancer type, chemotherapy compounds were heterogeneous, sample size was small (median: N = 34) and intention-to-treat analysis was lacking in 26/41 reports. Because of the methodological issues of included studies, the reviewed evidence should be considered as preliminary. Exercise, endurance, strength, balance, and sensorimotor training have been studied in low-to-moderate quality studies, while the evidence for other treatments is preliminary/inconclusive. We offer recommendation for the design of future trials on CIPN.
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Affiliation(s)
- Stefano Tamburin
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy.
| | - Susanna B Park
- Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
| | - Angelo Schenone
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI), University of Genoa, Italy; IRCCS San Martino Hospital, Genoa, Italy
| | - Elisa Mantovani
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy
| | - Mehrnaz Hamedani
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal and Infantile Sciences (DINOGMI), University of Genoa, Italy
| | - Paola Alberti
- Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Vesile Yildiz-Kabak
- Faculty of Physical Therapy and Rehabilitation, Hacettepe University, Ankara, Turkey
| | - Ian R Kleckner
- Department of Pain and Translational Symptom Science, University of Maryland School of Nursing, Baltimore, MD, USA
| | - Noah Kolb
- Department of Neurological Sciences, University of Vermont, Burlington, VT, USA
| | | | - Brendan L McNeish
- Department of Neurological Sciences, University of Vermont, Burlington, VT, USA
| | - Andreas A Argyriou
- Department of Neurology, "Saint Andrew's" State General Hospital of Patras, Patras, Greece
| | - Guido Cavaletti
- Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Ahmet Hoke
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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26
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Leen AJ, Yap DWT, Teo CB, Tan BKJ, Molassiotis A, Ishiguro H, Fan SWX, Sundar R, Soon YY, Bandla A. A Systematic Review and Meta-Analysis of the Effectiveness of Neuroprotectants for Paclitaxel-Induced Peripheral Neuropathy. Front Oncol 2022; 11:763229. [PMID: 35070969 PMCID: PMC8766304 DOI: 10.3389/fonc.2021.763229] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 12/07/2021] [Indexed: 12/17/2022] Open
Abstract
Background Paclitaxel-induced peripheral neuropathy (PIPN) is a disabling side effect of paclitaxel with few effective preventive strategies. We aim to determine the efficacy of pharmacological and non-pharmacological neuroprotective interventions in preventing PIPN incidence. Methods Biomedical literature databases were searched from years 2000 to 2021 for trials comparing neuroprotective interventions and control. Meta-analysis was performed using the random-effects model. The primary outcome was the incidence of PIPN. Results Of 24 relevant controlled trials, 14 were eligible for meta-analysis. Pooled results from seven non-pharmacological trials were associated with a statistically significant 48% relative reduction of PIPN risk with low heterogeneity. Conversely, pooled results from six pharmacological trials were associated with a significant 20% relative reduction of PIPN risk with moderate heterogeneity. Both pharmacological and non-pharmacological approaches appear effective in reducing PIPN incidence in the treatment arm compared to control (pooled RR < 1). Conclusion Current evidence suggests that both interventions may reduce PIPN risk. Non-pharmacological interventions appear more effective than pharmacological interventions.
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Affiliation(s)
- Alisha Joan Leen
- School of Medicine, National University of Ireland (NUI) Galway, Galway, Ireland.,Department of Haematology-Oncology, National University Health System, Singapore, Singapore.,The N.1 Institute for Health, National University of Singapore, Singapore, Singapore
| | - Dominic Wei Ting Yap
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Chong Boon Teo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Benjamin Kye Jyn Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Alex Molassiotis
- School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, Hong Kong SAR, China
| | - Hiroshi Ishiguro
- Department of Medical Oncology, International University of Health and Welfare Narita Hospital, Chiba, Japan
| | - Sarah Wei Xian Fan
- The N.1 Institute for Health, National University of Singapore, Singapore, Singapore
| | - Raghav Sundar
- Department of Haematology-Oncology, National University Health System, Singapore, Singapore.,The N.1 Institute for Health, National University of Singapore, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,National University Cancer Institute, National University Health System, Singapore, Singapore
| | - Yu Yang Soon
- Department of Radiation Oncology, National University Health System, Singapore, Singapore
| | - Aishwarya Bandla
- The N.1 Institute for Health, National University of Singapore, Singapore, Singapore.,National University Cancer Institute, National University Health System, Singapore, Singapore
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27
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Coolbrandt A, Vancoille K, Dejaeger E, Peeters H, Laenen A, Neven P, Punie K, Wildiers H. Preventing taxane-related peripheral neuropathy, pain and nail toxicity: a prospective self-controlled trial comparing hilotherapy with frozen gloves in early breast cancer. Breast Cancer Res Treat 2022; 192:293-301. [PMID: 34982322 DOI: 10.1007/s10549-021-06477-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 12/02/2021] [Indexed: 11/02/2022]
Abstract
PURPOSE The prevention of taxane-related toxicities at the extremities is highly important for patients' treatment and quality-of-life. Several studies endorse hand/foot-cooling using frozen gloves as a prophylactic intervention. Unlike frozen gloves, hilotherapy produces cooling at a constant temperature. Comparative data with frozen gloves are unavailable. METHODS This prospective self-controlled study explores the efficacy of hilotherapy at the right hand and foot compared to frozen gloves at the left in patients with early breast cancer treated with weekly paclitaxel 80 mg/m2 or three-weekly docetaxel 75 mg/m2. Patient-reported outcomes were collected at baseline, 6, 12, 18 and 24 weeks after the start of treatment. Primary and secondary endpoints were the incidence of any-grade and ≥ grade 2 side-effects (peripheral neuropathy, pain and nail toxicities), and perceived comfort of both interventions. RESULTS Sixty-two patients participated. The incidence of any-grade side-effects was similar on both sides, 85.5% with hilotherapy and 90.3% with frozen gloves (p = 1.000). The incidence of ≥ grade 2 side-effects at the extremities was significantly lower with hilotherapy: 43.6% compared to 61.3% with frozen gloves (p = 0.013). Perceived comfort was significantly better for hilotherapy than for frozen gloves (p < 0.0001). CONCLUSIONS Compared to frozen gloves, continuous cooling of hands and feet using hilotherapy produces better prevention of ≥ grade 2 patient-reported side-effects at the extremities (peripheral neuropathy, pain and nail toxicities). Perceived comfort was significantly better for hilotherapy. From a clinical and patient perspective, hilotherapy is a better alternative for preventing clinically significant taxane-related side-effects.
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Affiliation(s)
- Annemarie Coolbrandt
- Department of Oncology Nursing, University Hospitals Leuven, Herestraat 49, Leuven, Belgium. .,Department of Public Health and Primary Care, Academic Centre for Nursing and Midwifery, KU Leuven, Leuven, Belgium.
| | - K Vancoille
- Department of Oncology Nursing, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
| | - E Dejaeger
- Department of Oncology Nursing, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
| | - H Peeters
- Department of Oncology Nursing, University Hospitals Leuven, Herestraat 49, Leuven, Belgium
| | - A Laenen
- Interuniversity Centre for Biostatistics and Statistical Bioinformatics, KU Leuven, Leuven, Belgium
| | - P Neven
- Multidisciplinary Breast Centre, University Hospitals Leuven, Leuven, Belgium
| | - K Punie
- Multidisciplinary Breast Centre, University Hospitals Leuven, Leuven, Belgium
| | - H Wildiers
- Multidisciplinary Breast Centre, University Hospitals Leuven, Leuven, Belgium
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28
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Mezzanotte JN, Grimm M, Shinde NV, Nolan T, Worthen-Chaudhari L, Williams NO, Lustberg MB. Updates in the Treatment of Chemotherapy-Induced Peripheral Neuropathy. Curr Treat Options Oncol 2022; 23:29-42. [PMID: 35167004 PMCID: PMC9642075 DOI: 10.1007/s11864-021-00926-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/06/2021] [Indexed: 12/16/2022]
Abstract
OPINION STATEMENT Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity associated with treatment with platinum-based agents, taxanes, vinca alkaloids, and other specific agents. The long-term consequences of this condition can result in decreased patient quality of life and can lead to reduced dose intensity, which can negatively impact disease outcomes. There are currently no evidence-based preventative strategies for CIPN and only limited options for treatment. However, there are several strategies that can be utilized to improve patient experience and outcomes as more data are gathered in the prevention and treatment setting. Before treatment, patient education on the potential side effects of chemotherapy is key, and although trials have been limited, recommending exercise and a healthy lifestyle before and while undergoing chemotherapy may provide some overall benefit. In patients who develop painful CIPN, our approach is to offer duloxetine and titrate up to 60 mg daily. Chemotherapy doses may also need to be reduced if intolerable symptoms develop during treatment. Some patients may also try acupuncture and physical therapy to help address their symptoms, although this can be limited by cost, time commitment, and patient motivation. Additionally, data on these modalities are currently limited, as studies are ongoing. Overall, approaching each patient on an individual level and tailoring treatment options for them based on overall physical condition, their disease burden, goals of care and co-morbid health conditions, and willingness to trial different approaches is necessary when addressing CIPN.
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Affiliation(s)
- Jessica N. Mezzanotte
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, Room 334B, Columbus, OH 43210
| | - Michael Grimm
- The Ohio State University Comprehensive Cancer Center, 460 W. 10th Avenue, Columbus, OH 43210
| | - Namrata V. Shinde
- Department of Radiology, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, Columbus, OH 43210
| | - Timiya Nolan
- The Ohio State University College of Nursing, 1585 Neil Avenue, Columbus, OH 43210
| | - Lise Worthen-Chaudhari
- Department of Physical Medicine and Rehabilitation, The Ohio State University Wexner Medical Center, 480 Medical Center Drive, Dodd Hall, Suite 1060, Columbus, OH 43210
| | - Nicole O. Williams
- Department of Medical Oncology, The Ohio State University Wexner Medical Center, 1800 Cannon Drive, 1310K Lincoln Tower, Columbus, OH 43210
| | - Maryam B. Lustberg
- Smilow Cancer Hospital/Yale Cancer Center, 35 Park Street, New Haven, CT 06519
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29
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Oneda E, Meriggi F, Zanotti L, Zaina E, Bighè S, Andreis F, Rueda S, Zaniboni A. Innovative Approach for the Prevention of Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Pilot Study With the Hilotherm Device, the Poliambulanza Hospital Experience. Integr Cancer Ther 2021; 19:1534735420943287. [PMID: 32856475 PMCID: PMC7457652 DOI: 10.1177/1534735420943287] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse event of taxanes, with no effective prevention or treatment available and a highly negative impact on patient quality of life. The aim of this study is to asses that the constant application of cooled cuffs on the hands and feet prevent and mitigate CIPN. METHODS Patients with breast, gynecologic, and pancreatic cancer who received weekly paclitaxel (PTX), PTX/carboplatin, and nab-paclitaxel (nab-PTX)/gemcitabine for any indication at the therapeutic scheduled dosage were included in this prospective study. Hilotherm Chemo care device forms a closed-loop system with cuffs and tubes through which a coolant flows at a temperature of 10 °C. CIPN was monitored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (edition 3.0), and the tolerability and side effects were scored by using the Common Terminology Criteria for Adverse Events (T4.03 2017). RESULTS To date, we have enrolled 64 patients. Of these, 54 (84%) completed all cooling cycles. Continuous cooling was well tolerated by all patients. No patients had grade >2 CIPN or had serious or lasting adverse events as a result of Hilotherapy. The median time to CIPN onset was 77 days for the entire population. CONCLUSION Hilotherapy has good effectiveness and tolerability and seems to be able to prevent or reduce the symptoms of CIPN. We are still recruiting patients to obtain more data and to collect data at 3 months after the end of chemotherapy. Prospective studies seem to be warranted.
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Affiliation(s)
| | | | | | | | - Sara Bighè
- Fondazione Poliambulanza, Brescia, Italy
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30
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Merheb D, Dib G, Zerdan MB, Nakib CE, Alame S, Assi HI. Drug-Induced Peripheral Neuropathy: Diagnosis and Management. Curr Cancer Drug Targets 2021; 22:49-76. [PMID: 34288840 DOI: 10.2174/1568009621666210720142542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 05/07/2021] [Accepted: 05/21/2021] [Indexed: 01/09/2023]
Abstract
Peripheral neuropathy comes in all shapes and forms and is a disorder which is found in the peripheral nervous system. It can have an acute or chronic onset depending on the multitude of pathophysiologic mechanisms involving different parts of nerve fibers. A systematic approach is highly beneficial when it comes to cost-effective diagnosis. More than 30 causes of peripheral neuropathy exist ranging from systemic and auto-immune diseases, vitamin deficiencies, viral infections, diabetes, etc. One of the major causes of peripheral neuropathy is drug induced disease, which can be split into peripheral neuropathy caused by chemotherapy or by other medications. This review deals with the latest causes of drug induced peripheral neuropathy, the population involved, the findings on physical examination and various workups needed and how to manage each case.
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Affiliation(s)
- Diala Merheb
- Department of Internal Medicine, Saint George Hospital University Medical Center, Beirut, Lebanon
| | - Georgette Dib
- Department of Internal Medicine, Division of Neurology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Maroun Bou Zerdan
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Clara El Nakib
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Saada Alame
- Department of Pediatrics, Clemenceau Medical Center, Faculty of Medical Sciences, Lebanese University, Beirut,, Lebanon
| | - Hazem I Assi
- Department of Internal Medicine Naef K. Basile Cancer Institute American University of Beirut Medical Center Riad El Solh 1107 2020 Beirut, Lebanon
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31
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Oneda E, Abeni C, Zanotti L, Zaina E, Bighè S, Zaniboni A. Chemotherapy-induced neurotoxicity in the treatment of gynecological cancers: State of art and an innovative approach for prevention. World J Clin Oncol 2021; 12:458-467. [PMID: 34189069 PMCID: PMC8223716 DOI: 10.5306/wjco.v12.i6.458] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/29/2021] [Accepted: 06/04/2021] [Indexed: 02/06/2023] Open
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect that occurs in 20% of ovarian cancer patients treated with the combination of carboplatin/paclitaxel (CP). This toxicity is directly correlated with the dose of paclitaxel administered. Several studies have investigated whether different formulations of taxane can induce this side effect at a lower rate, but, unfortunately, no significant improvement was obtained. CIPN can be disabling in the daily lives of patients and can cause dose reduction or early termination of the treatment. Neuropathy can last for months and even years after its onset. Moreover, patients responsive to CP treatment are candidates for a reintroduction of the same drugs when disease relapse occurs, and residual neuropathy can affect the continuation of treatment. There are no approved drugs that mitigate or prevent the onset of CIPN. In this review, we summarize the evidence regarding the incidence of CIPN with different taxane formulations, regimen schedules and prevention systems. In particular, the Hilotherm® Chemo care device is a regional cooling system that lowers the temperature of the hands and feet to reduce the flow of chemotherapy into the capillaries. We used hilotherapy during chemotherapy infusion to prevent the onset of CIPN. Updated data from 44 ovarian cancer patients treated with 6 cycle of CP show that hilotherapy was well tolerated; only two patients (4.5%) stopped hilotherapy because of cold intolerance, and only one patient (2.2%) experienced grade ≥ 2 CIPN.
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Affiliation(s)
- Ester Oneda
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Chiara Abeni
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Laura Zanotti
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Elisabetta Zaina
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Sara Bighè
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Alberto Zaniboni
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
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32
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Popescu RA, Roila F, Arends J, Metro G, Lustberg M. Supportive Care: Low Cost, High Value. Am Soc Clin Oncol Educ Book 2021; 41:1-11. [PMID: 33830830 DOI: 10.1200/edbk_320041] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Supportive care aims to prevent and manage adverse effects of cancer and its treatment across the entire disease continuum. Research and clinical experience in dedicated centers have demonstrated that early appropriate supportive care interventions improve symptoms, quality of life, and overall survival in a cost-effective manner. The challenge is to assess symptoms and needs with validated tools regularly and, ideally, between clinic appointments; electronic patient-reported outcome measures and dedicated easily accessible supportive care units can help. As management of certain problems improves, others come to the fore. Cancer-related fatigue and malnutrition are very frequent and need regular screening, assessment of treatable causes, and early intervention to improve. Pharmacologic agents and phytopharmaceuticals are of little use, but other interventions are valuable: physical exercise, counseling on fatigue, and cognitive behavioral therapy/mind-body interventions (e.g., for fatigue). Nutrition should be oral, rich in proteins, and accompanied by muscle training adapted to the patient's condition. Psychological and societal counseling is often useful; nausea or other problems such as gastrointestinal dysmotility or metabolic derangements must be tackled. Chemotherapy-induced peripheral neuropathy frequently worsens quality of life and has no established prevention strategy (notwithstanding current interest in cryotherapy and compression therapy) and thus requires careful assessment of patient predisposition to develop it with the consideration of feasible dose and treatment alternatives. When painful, duloxetine helps. Nonpharmacologic strategies, including acupuncture, physical exercise, cryotherapy/compression, and scrambler therapy, are promising but require large phase III trials to become the accepted standard. Personalization of chemotherapy, dependent on realistic goals, is key.
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Affiliation(s)
| | - Fausto Roila
- Medical Oncology, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy
| | - Jann Arends
- Department of Medicine I, Faculty of Medicine, Medical Center-University of Freiburg, University of Freiburg, Freiburg, Germany
| | - Giulio Metro
- Medical Oncology, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy
| | - Maryam Lustberg
- Division of Medical Oncology, The Ohio State University, Columbus, OH
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33
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Li Y, Lustberg MB, Hu S. Emerging Pharmacological and Non-Pharmacological Therapeutics for Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy. Cancers (Basel) 2021; 13:cancers13040766. [PMID: 33673136 PMCID: PMC7918689 DOI: 10.3390/cancers13040766] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/04/2021] [Accepted: 02/08/2021] [Indexed: 12/25/2022] Open
Abstract
Simple Summary Chemotherapy-induced peripheral neuropathy (CIPN) is a common and persistent complication of commonly used chemotherapy drugs. This article provides an overview of emerging therapeutics for the prevention and treatment of CIPN and focuses on pharmacological strategies that are derived from novel mechanistic insights and have the potential to be translated into clinically beneficial approaches. It is our contention to call for fostering collaboration between basic and clinical researchers to improve the development of effective strategies. Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event of several first-line chemotherapeutic agents, including platinum compounds, taxanes, vinca alkaloids, thalidomide, and bortezomib, which negatively affects the quality of life and clinical outcome. Given the dearth of effective established agents for preventing or treating CIPN, and the increasing number of cancer survivors, there is an urgent need for the identification and development of new, effective intervention strategies that can prevent or mitigate this debilitating side effect. Prior failures in the development of effective interventions have been due, at least in part, to a lack of mechanistic understanding of CIPN and problems in translating this mechanistic understanding into testable hypotheses in rationally-designed clinical trials. Recent progress has been made, however, in the pathogenesis of CIPN and has provided new targets and pathways for the development of emerging therapeutics that can be explored clinically to improve the management of this debilitating toxicity. This review focuses on the emerging therapeutics for the prevention and treatment of CIPN, including pharmacological and non-pharmacological strategies, and calls for fostering collaboration between basic and clinical researchers to improve the development of effective strategies.
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Affiliation(s)
- Yang Li
- Division of Pharmaceutics and Pharmacology, College of Pharmacy & Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA;
| | - Maryam B. Lustberg
- Comprehensive Cancer Center, Department of Medical Oncology, The Ohio State University, Columbus, OH 43210, USA;
| | - Shuiying Hu
- Division of Pharmaceutics and Pharmacology, College of Pharmacy & Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA;
- Correspondence: ; Tel.: +1-614-685-8028
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34
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Jordan B, Margulies A, Cardoso F, Cavaletti G, Haugnes HS, Jahn P, Le Rhun E, Preusser M, Scotté F, Taphoorn MJB, Jordan K. Systemic anticancer therapy-induced peripheral and central neurotoxicity: ESMO-EONS-EANO Clinical Practice Guidelines for diagnosis, prevention, treatment and follow-up. Ann Oncol 2020; 31:1306-1319. [PMID: 32739407 DOI: 10.1016/j.annonc.2020.07.003] [Citation(s) in RCA: 183] [Impact Index Per Article: 36.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 07/06/2020] [Accepted: 07/06/2020] [Indexed: 12/14/2022] Open
Affiliation(s)
- B Jordan
- Department of Neurology, University Hospital of Heidelberg, Heidelberg, Germany
| | - A Margulies
- European Oncology Nursing Society, Brussels, Belgium
| | - F Cardoso
- Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal
| | - G Cavaletti
- Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - H S Haugnes
- Department of Oncology, University Hospital of North Norway, Tromsoe, Norway; Institute of Medicine, UIT - The Arctic University, Tromsoe, Norway
| | - P Jahn
- University of Halle, Nursing Research Unit, Halle, Germany
| | - E Le Rhun
- University of Lille, Inserm, U-1192, Lille, France; CHU Lille, Neuro-oncology, General and Stereotaxic Neurosurgery Service, Lille, France; Breast Cancer Department, Oscar Lambret Center, Lille cedex, France; Department of Neurology and Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland
| | - M Preusser
- Clinical Division of Oncology, Comprehensive Cancer Center CNS Tumours Unit, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - F Scotté
- Gustave Roussy Cancer Campus, Interdisciplinary Cancer Course Department, Villejuif, France
| | - M J B Taphoorn
- Department of Neurology, Leiden University Medical Center and Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands
| | - K Jordan
- Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany
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35
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Bailey AG, Brown JN, Hammond JM. Cryotherapy for the prevention of chemotherapy-induced peripheral neuropathy: A systematic review. J Oncol Pharm Pract 2020; 27:156-164. [PMID: 32955997 DOI: 10.1177/1078155220959431] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Chemotherapy induced peripheral neuropathy (CIPN) is an adverse effect of certain chemotherapy agents that can result in dose reductions, permanent nerve damage, and chronic pain. Although pharmacological agents have been studied in this setting, there is no standard of care for the prevention of CIPN. Thus, the objective of this systematic review is to assess the efficacy and safety of cryotherapy for the prevention of CIPN. DATA SOURCES PubMed (1946 to February 2020) and Embase (1947 to February 2020) were utilized to conduct a literature search using the following search terms: antineoplastic agent(s), taxoid(s), or chemotherapy and neuralgia, peripheral nervous system diseases, peripheral neuropathy, or paclitaxel-induced peripheral neuropathy and cryotherapy, cryotherapy device, hypothermia, low temperature procedures, or ice. DATA SUMMARY A total of 11 studies were included in the final assessment. Results of this systematic review indicate that the efficacy of cryotherapy in preventing CIPN is conflicting. This may be due to studies utilizing differing cryotherapy administration methods, study design, and including only a small number of patients. All included studies utilized cryotherapy with taxane-based chemotherapy treatments and cooling gloves and socks was the most common method of administration. Overall, cryotherapy was well-tolerated and no serious adverse effects were noted. CONCLUSIONS Due to the absence of serious adverse effects, cryotherapy is a reasonable option to consider to prevent CIPN in patients receiving taxane-based chemotherapy. However, additional research is needed, including larger, better designed studies, to fully delineate the role of cryotherapy for CIPN.
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Affiliation(s)
- Andrea G Bailey
- Pharmacy Service, Durham Veterans Affairs Health Care System, Durham, NC, USA
| | - Jamie N Brown
- Pharmacy Service, Durham Veterans Affairs Health Care System, Durham, NC, USA
| | - Julia M Hammond
- Pharmacy Service, Durham Veterans Affairs Health Care System, Durham, NC, USA
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36
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Loprinzi CL, Lacchetti C, Bleeker J, Cavaletti G, Chauhan C, Hertz DL, Kelley MR, Lavino A, Lustberg MB, Paice JA, Schneider BP, Lavoie Smith EM, Smith ML, Smith TJ, Wagner-Johnston N, Hershman DL. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. J Clin Oncol 2020; 38:3325-3348. [PMID: 32663120 DOI: 10.1200/jco.20.01399] [Citation(s) in RCA: 555] [Impact Index Per Article: 111.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
PURPOSE To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors. METHODS An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update. RECOMMENDATIONS The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited.Additional information is available at www.asco.org/survivorship-guidelines.
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Affiliation(s)
| | | | | | | | | | | | - Mark R Kelley
- Indiana University School of Medicine, Indianapolis, IN
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