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Yuan X, Chen J, Shi D, Song J, Wang P, Cheng D, Yang C, Qiu X, Zhai C. Advanced esophageal cancer with bone metastases: Prognostic biomarkers and palliative treatment. Heliyon 2024; 10:e23510. [PMID: 38170113 PMCID: PMC10758821 DOI: 10.1016/j.heliyon.2023.e23510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 11/16/2023] [Accepted: 12/05/2023] [Indexed: 01/05/2024] Open
Abstract
Esophageal cancer (EC) is a common and devastating tumor of the upper digestive tract. Unfortunately, by the time any symptoms have manifested, the disease has often progressed to an advanced stage and is accompanied by macro- and micrometastases, including in the bones. The treatment of esophageal cancer with bone metastases remains clinically challenging, given the poor prognosis associated with this condition. Effective prognostic biomarkers can help medical staff choose the appropriate operation and treatment plan, that is for most beneficial for making patients. Current treatments for esophageal cancer with bone metastases include pain-relieving drugs, surgical therapy, radiotherapy (RT), chemotherapy (CT, including molecular-targeted drug therapy), endocrine therapy (ET), bisphosphonates (BPs) and interventional therapy. Of these robust measures, radiotherapy has emerged as a particularly promising therapy for bone metastases from esophageal cancer. Substantial progress has been made in radiation therapy techniques since the discovery of X-rays by Roentgen in 1895. In its palliative capacity, the key goals of radiotherapy are to relieve the patients' bone pain and debilitate effects, including relieving spinal cord compression, correcting the spinal deformity and restoring spinal stability. However, it is worth mentioning that RT for esophageal cancer has various side effects. Currently, the available studies focused exclusively on radiotherapy for ECBM are too small to draw any definitive conclusions, and each of these studies has significant limitations. In this review, in addition to the epidemiology described at the beginning, we will explore the current prognostic biomarkers and radiotherapy for esophageal cancer, with a particular focus on those with bone metastases.
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Affiliation(s)
- Xiaofeng Yuan
- The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Jun Chen
- Department of Orthopedics, Yixing People's Hospital, Yixing, China
| | - Dingsen Shi
- The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Jiaxun Song
- The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Pu Wang
- The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Dong Cheng
- The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Cheng Yang
- The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Xubin Qiu
- The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Chenjun Zhai
- Department of Orthopedics, Yixing People's Hospital, Yixing, China
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Tsvetkova D, Ivanova S. Application of Approved Cisplatin Derivatives in Combination Therapy against Different Cancer Diseases. Molecules 2022; 27:2466. [PMID: 35458666 PMCID: PMC9031877 DOI: 10.3390/molecules27082466] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 02/03/2023] Open
Abstract
The problems with anticancer therapy are resistance and toxicity. From 3000 Cisplatin derivatives tested as antitumor agents, most of them have been rejected, due to toxicity. The aim of current study is the comparison of therapeutic combinations of the currently applied in clinical practice: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, Heptaplatin, and Satraplatin. The literature data show that the strategies for the development of platinum anticancer agents and bypassing of resistance to Cisplatin derivatives and their toxicity are: combination therapy, Pt IV prodrugs, the targeted nanocarriers. The very important strategy for the improvement of the antitumor effect against different cancers is synergistic combination of Cisplatin derivatives with: (1) anticancer agents-Fluorouracil, Gemcitabine, Cytarabine, Fludarabine, Pemetrexed, Ifosfamide, Irinotecan, Topotecan, Etoposide, Amrubicin, Doxorubicin, Epirubicin, Vinorelbine, Docetaxel, Paclitaxel, Nab-Paclitaxel; (2) modulators of resistant mechanisms; (3) signaling protein inhibitors-Erlotinib; Bortezomib; Everolimus; (4) and immunotherapeutic drugs-Atezolizumab, Avelumab, Bevacizumab, Cemiplimab, Cetuximab, Durvalumab, Erlotinib, Imatinib, Necitumumab, Nimotuzumab, Nivolumab, Onartuzumab, Panitumumab, Pembrolizumab, Rilotumumab, Trastuzumab, Tremelimumab, and Sintilimab. An important approach for overcoming the drug resistance and reduction of toxicity of Cisplatin derivatives is the application of nanocarriers (polymers and liposomes), which provide improved targeted delivery, increased intracellular penetration, selective accumulation in tumor tissue, and enhanced therapeutic efficacy. The advantages of combination therapy are maximum removal of tumor cells in different phases; prevention of resistance; inhibition of the adaptation of tumor cells and their mutations; and reduction of toxicity.
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Affiliation(s)
- Dobrina Tsvetkova
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University-Sofia, Dunav Str. 2, 1000 Sofia, Bulgaria
| | - Stefka Ivanova
- Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy, Medical University-Pleven, Kliment Ohridski Str. 1, 5800 Pleven, Bulgaria;
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Yan MH, Liu F, Qu BL, Cai BN, Yu W, Dai XK. Induction chemotherapy with albumin-bound paclitaxel plus lobaplatin followed by concurrent radiochemotherapy for locally advanced esophageal cancer. World J Gastrointest Oncol 2021; 13:1781-1790. [PMID: 34853650 PMCID: PMC8603460 DOI: 10.4251/wjgo.v13.i11.1781] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/18/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Albumin-bound paclitaxel (ABP) has been used as second- and higher-line treatments for advanced esophageal cancer, and its efficacy and safety have been well demonstrated. Lobaplatin (LBP) is a third-generation platinum antitumor agent; compared with the first two generations of platinum agents, it has lower toxicity and has been approved for the treatment of breast cancer, small cell lung cancer, and chronic granulocytic leukemia. However, its role in the treatment of esophageal cancer warrants further investigations.
AIM To investigate the efficacy and safety of induction chemotherapy with ABP plus LBP followed by concurrent radiochemotherapy (RCT) for locally advanced esophageal cancer.
METHODS Patients with pathologically confirmed advanced esophageal squamous cell carcinoma (ESCC) at our hospital were enrolled in this study. All patients were treated with two cycles of induction chemotherapy with ABP plus LBP followed by concurrent RCT: ABP 250 mg/m2, ivgtt, 30 min, d1, every 3 wk; and LBP, 30 mg/m2, ivgtt, 2 h, d1, every 3 wk. A total of four cycles were scheduled. The dose of the concurrent radiotherapy was 56-60 Gy/28-30 fractions, 1.8-2.0 Gy/fraction, and 5 fractions/wk.
RESULTS A total of 29 patients were included, and 26 of them completed the treatment protocol. After the induction chemotherapy, the objective response rate (ORR) was 61.54%, the disease control rate (DCR) was 88.46%, and the progressive disease (PD) rate was 11.54%; after the concurrent RCT, the ORR was 76.92%, the DCR was 88.46%, and the PD rate was 11.54%. The median progression-free survival was 11.1 mo and the median overall survival was 15.83 mo. Cox multivariate analysis revealed that two cycles of induction chemotherapy followed by concurrent RCT significantly reduced the risk of PD compared with two cycles of chemotherapy alone (P = 0.0024). Non-hematologic toxicities were tolerable, and the only grade 3 non-hematologic toxicity was radiation-induced esophagitis (13.79%). The main hematologic toxicity was neutropenia, and no grade 4 adverse event occurred.
CONCLUSION Induction chemotherapy with ABP plus LBP followed by concurrent RCT is effective in patients with locally advanced ESCC, with mild adverse effects. Thus, this protocol is worthy of clinical promotion and application.
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Affiliation(s)
- Mao-Hui Yan
- Department of Radiotherapy, The First Medical Center of the Chinese People's Liberation Army (PLA) General Hospital, Beijing 100853, China
| | - Fang Liu
- Department of Radiotherapy, The First Medical Center of the Chinese People's Liberation Army (PLA) General Hospital, Beijing 100853, China
| | - Bao-Lin Qu
- Department of Radiotherapy, The First Medical Center of the Chinese People's Liberation Army (PLA) General Hospital, Beijing 100853, China
| | - Bo-Ning Cai
- Department of Radiotherapy, The First Medical Center of the Chinese People's Liberation Army (PLA) General Hospital, Beijing 100853, China
| | - Wei Yu
- Department of Radiotherapy, The First Medical Center of the Chinese People's Liberation Army (PLA) General Hospital, Beijing 100853, China
| | - Xiang-Kun Dai
- Department of Radiotherapy, The First Medical Center of the Chinese People's Liberation Army (PLA) General Hospital, Beijing 100853, China
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Yan MH, Hou XB, Cai BN, Qu BL, Dai XK, Liu F. Neoadjuvant chemoradiotherapy plus surgery in the treatment of potentially resectable thoracic esophageal squamous cell carcinoma. World J Clin Cases 2020; 8:6315-6321. [PMID: 33392312 PMCID: PMC7760436 DOI: 10.12998/wjcc.v8.i24.6315] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 10/08/2020] [Accepted: 11/02/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND In recent years, neoadjuvant chemoradiotherapy (NCRT) combined with surgery has been gradually applied in patients with locally advanced thoracic esophageal cancer, but its effectiveness and safety remains unclear. In this clinical trial, we prospectively investigated the efficacy and safety of NCRT plus surgery in the treatment of thoracic esophageal squamous cell carcinoma (TESCC).
AIM To investigate the efficacy and safety of NCRT combined with surgery in the treatment of potentially resectable TESCC.
METHODS Thirty patients with advanced TESCC hospitalized in our hospital from July 2016 to June 2019 were prospectively studied. All patients received NCRT, which included intensity modulated conformal radiotherapy (40-44 Gy/20-22f, 2 Gy/f) and chemotherapy (paclitaxel 150-175 mg/m2d1, 22 + lobaplatin 25-30 mg/m2d2, 23 for two cycles). Surgery was performed after radiotherapy and chemotherapy. The effectiveness and safety of these treatments were observed.
RESULTS Among these 30 patients, complete response was achieved in two cases (6.7%) and partial response in 26 cases (86.7%), yielding an objective response rate of 100%. All patients underwent radical surgery successfully. The R0 resection rate was 100%, and the pathologic complete response rate was 33.3%. The incidence of grade III- IV granulocytopenia was 10% during the NCRT, and anastomotic leakage occurred in one patient after surgery.
CONCLUSION For patients with potentially resectable TESCC, NCRT can effectively reduce the tumor size, increase R0 resection rate, and achieve obvious pathological degradation, with mild adverse reactions. Thus, it is worthy of wider clinical application.
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Affiliation(s)
- Mao-Hui Yan
- Department of Radiotherapy, The First Medical Center of the Chinese PLA General Hospital, Beijing 100853, China
| | - Xiao-Bin Hou
- Department of Thoracic Surgery, The First Medical Center of the Chinese PLA General Hospital, Beijing 100853, China
| | - Bo-Ning Cai
- Department of Radiotherapy, The First Medical Center of the Chinese PLA General Hospital, Beijing 100853, China
| | - Bao-Lin Qu
- Department of Radiotherapy, The First Medical Center of the Chinese PLA General Hospital, Beijing 100853, China
| | - Xiang-Kun Dai
- Department of Radiotherapy, The First Medical Center of the Chinese PLA General Hospital, Beijing 100853, China
| | - Fang Liu
- Department of Radiotherapy, The First Medical Center of the Chinese PLA General Hospital, Beijing 100853, China
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Zhao Z, Wen Y, Liao D, Miao J, Gui Y, Cai H, Chen Y, Wei M, Jia Q, Tian H, Sun M, Zhang Y, Feng G, Du X. Single-Agent Versus Double-Agent Chemotherapy in Concurrent Chemoradiotherapy for Esophageal Squamous Cell Carcinoma: Prospective, Randomized, Multicenter Phase II Clinical Trial. Oncologist 2020; 25:e1900-e1908. [PMID: 32864805 PMCID: PMC8108049 DOI: 10.1634/theoncologist.2020-0808] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 08/14/2020] [Indexed: 02/06/2023] Open
Abstract
LESSONS LEARNED The efficacy of single-agent chemotherapy was not significantly different from that of double-agent chemotherapy in concurrent chemoradiotherapy for inoperable esophageal squamous cell carcinoma. Single-agent concurrent chemoradiotherapy had lower gastrointestinal and hematologic toxicity. Overall survival and progression-free survival were not significantly different between single- and double-agent concurrent chemoradiotherapy. BACKGROUND This multicenter, randomized, phase II trial aimed to compare the efficacy and safety of single-agent concurrent chemoradiotherapy using the oral fluoropyrimidine S-1 with those of double-agent concurrent chemoradiotherapy using S-1 and cisplatin in patients with inoperable esophageal squamous cell carcinoma. METHODS Patients with inoperable esophageal squamous cell carcinoma (clinical stages I to III) were randomly allocated to the single-agent group (S-1) or the double-agent group (S-1/cisplatin). The concurrent intensity-modulated radiation therapy plan was similar for both groups: planning target volume 1.8 Gy/f*30-33f and planning gross target volume of 2 Gy/f*30-33f. The primary outcome measure was the endoscopic complete response rate. RESULTS Of the 105 patients randomized, 89 were assessable. The endoscopic complete response rate was 46.9% (23/49) in the single-agent group and 52.5% (21/40) in double-agent group. The median progression-free survival within a median follow-up of 23 months was 20 and 21 months, respectively. The median overall survival was 26 months and not reached, respectively. Grade 3 hematological toxicities occurred in 4.1% and 27.5% of the patients in the single- and the double-agent group, respectively. CONCLUSION Single-agent chemotherapy in concurrent chemoradiotherapy for inoperable esophageal squamous cell carcinoma has good efficacy and safety, thus warranting a phase III trial.
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Affiliation(s)
- Zhenhuan Zhao
- Department of Oncology, Mianyang Central HospitalMianyangPeople's Republic of China
| | - Yixue Wen
- Department of Oncology, Mianyang Central HospitalMianyangPeople's Republic of China
| | - Dongbiao Liao
- Department of Oncology, Mianyang Central HospitalMianyangPeople's Republic of China
| | - Jidong Miao
- Department of Oncology, Zigong Fourth People's HospitalZi GongPeople's Republic of China
| | - Yan Gui
- Department of Oncology, Affiliated Hospital of North Sichuan Medical CollegeNan ChongPeople's Republic of China
| | - Hongwei Cai
- Department of Oncology, Lang Zhong People's HospitalLang ZhongPeople's Republic of China
| | - Yang Chen
- Department of Oncology, Jianyang People's HospitalJian YangPeople's Republic of China
| | - Min Wei
- Department of Oncology, Ziyang People's HospitalZi YangPeople's Republic of China
| | - Qiang Jia
- Department of Oncology, Jiangyou Second People's HospitalJiang YouPeople's Republic of China
| | - Honggang Tian
- Department of Oncology, Jiangyou People's HospitalJiang YouPeople's Republic of China
| | - Mingqiang Sun
- Department of Oncology, Guangyuan First People's HospitalGuang YuanPeople's Republic of China
| | - Yu Zhang
- Department of Oncology, Mianyang Central HospitalMianyangPeople's Republic of China
| | - Gang Feng
- Department of Oncology, Mianyang Central HospitalMianyangPeople's Republic of China
| | - Xiaobo Du
- Department of Oncology, Mianyang Central HospitalMianyangPeople's Republic of China
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Pan S, Sun Y, Sui D, Yang T, Fu S, Wang J, Hui B, Xi R, He C, Zhang X. Lobaplatin promotes radiosensitivity, induces apoptosis, attenuates cancer stemness and inhibits proliferation through PI3K/AKT pathway in esophageal squamous cell carcinoma. Biomed Pharmacother 2018; 102:567-574. [PMID: 29597090 DOI: 10.1016/j.biopha.2018.03.109] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Revised: 03/16/2018] [Accepted: 03/17/2018] [Indexed: 02/07/2023] Open
Abstract
Radiotherapy is one of the common treatments for esophageal squamous cell carcinoma (ESCC). Yet, local recurrence led by radioresistance is still not solved. Lobaplatin (LBP) is known to have powerful clinical anti-tumor activities in various tumors, but its effect in radiotherapy is rarely studied. Here we report that LBP is a promising radiosensitizer for ESCC. We treated ESCC cells with LBP and radiation, both separately and in combination. Untreated cells were set as control groups. We found that LBP inhibited ESCC cell growth and enhanced their radiosensitivity. LBP also impeded the tumor growth in vivo. LBP combined with radiation significantly increased ESCC cell apoptosis. Meanwhile, LBP obviously decreased the expression of cancer stem cells biomarker CD271 both in vitro and in vivo. The molecular mechanism was related to the downregulation of Bcl-2/Bax ratio, PI3K and p-AKT (Ser473) expression. Taken together, our findings indicated that LBP could enhance the radiosensitivity of ESCC cells by increasing radiation-induced apoptosis, attenuating cancer stemness and inhibiting PI3K/AKT pathway. These results provide a foundation for the combined therapy of radiation and LBP for ESCC in clinical practice.
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Affiliation(s)
- Shupei Pan
- Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yuchen Sun
- Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Donghu Sui
- GuiZhou EverGreen Pharmaceutical Company Limited, Guizhou, China
| | - Tian Yang
- Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Shenbo Fu
- Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jizhao Wang
- The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Beina Hui
- Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Ruxing Xi
- The Fourth Department of Gynecological Tumor, The Shaanxi Province Oncology Hospital, Xi'an, Shaanxi, China
| | - Chenchen He
- Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Xiaozhi Zhang
- Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
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Antitumor activity of Lobaplatin against esophageal squamous cell carcinoma through caspase-dependent apoptosis and increasing the Bax/Bcl-2 ratio. Biomed Pharmacother 2017; 95:447-452. [DOI: 10.1016/j.biopha.2017.08.119] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 08/26/2017] [Accepted: 08/28/2017] [Indexed: 02/06/2023] Open
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