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Shakerzadeh E. Li@B40 and Na@B40 fullerenes serving as efficient carriers for anticancer nedaplatin drug: A quantum chemical study. COMPUT THEOR CHEM 2021. [DOI: 10.1016/j.comptc.2021.113339] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Chikazawa K, Netsu S, Imai K, Ishiguro A, Kimura A, Wang L, Kuwata T, Konno R. Nedaplatin use in patients with hypersensitivity reaction episodes to carboplatin. Taiwan J Obstet Gynecol 2021; 59:546-550. [PMID: 32653127 DOI: 10.1016/j.tjog.2020.05.013] [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] [Accepted: 03/11/2020] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE To evaluate the benefits of nedaplatin treatment in patients with a history of hypersensitivity reactions to carboplatin. MATERIALS AND METHODS We retrospectively reviewed the medical records of patients with ovarian, fallopian, and peritoneal cancers and with a history of hypersensitivity to carboplatin between January 2010 and December 2016 at the Department of Gynecology in the Saitama Medical Center associated with Jichi Medical University. We studied the response rate to treatment with a nedaplatin-based regimen compared to that of a carboplatin regimen. Fisher's exact test was used to determine statistical significance. RESULTS Thirty-one patients with a past hypersensitivity to carboplatin were treated with nedaplatin-based regimen, while ten patients were treated with other drugs. The response rates in the nedaplatin- and non-nedaplatin-treated patient groups were 71.4% and 30.0%, respectively (P = 0.021). Among all the patients, only one experienced hypersensitivity reaction to nedaplatin. CONCLUSION The nedaplatin regimen following hypersensitivity to carboplatin was safe, feasible, and effective in achieving complete or partial response.
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Affiliation(s)
- Kenro Chikazawa
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Japan.
| | - Sachiho Netsu
- Department of Gynecology, Cancer Institute Hospital, Tokyo, Japan
| | - Ken Imai
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Japan
| | - Aya Ishiguro
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Japan
| | - Azusa Kimura
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Japan
| | - Liangcheng Wang
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Japan
| | - Tomoyuki Kuwata
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Japan
| | - Ryo Konno
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Japan
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The Protein-Binding Behavior of Platinum Anticancer Drugs in Blood Revealed by Mass Spectrometry. Pharmaceuticals (Basel) 2021; 14:ph14020104. [PMID: 33572935 PMCID: PMC7911130 DOI: 10.3390/ph14020104] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 01/22/2021] [Accepted: 01/26/2021] [Indexed: 02/06/2023] Open
Abstract
Cisplatin and its analogues are widely used as chemotherapeutic agents in clinical practice. After being intravenously administrated, a substantial amount of platinum will bind with proteins in the blood. This binding is vital for the transport, distribution, and metabolism of drugs; however, toxicity can also occur from the irreversible binding between biologically active proteins and platinum drugs. Therefore, it is very important to study the protein-binding behavior of platinum drugs in blood. This review summarizes mass spectrometry-based strategies to identify and quantitate the proteins binding with platinum anticancer drugs in blood, such as offline high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC–ICP-MS) combined with electrospray ionization mass spectrometry (ESI-MS/MS) and multidimensional LC–ESI-MS/MS. The identification of in vivo targets in blood cannot be accomplished without first studying the protein-binding behavior of platinum drugs in vitro; therefore, relevant studies are also summarized. This knowledge will further our understanding of the pharmacokinetics and toxicity of platinum anticancer drugs, and it will be beneficial for the rational design of metal-based anticancer drugs.
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Bian M, Sun Y, Liu Y, Xu Z, Fan R, Liu Z, Liu W. A Gold(I) Complex Containing an Oleanolic Acid Derivative as a Potential Anti‐Ovarian‐Cancer Agent by Inhibiting TrxR and Activating ROS‐Mediated ERS. Chemistry 2020; 26:7092-7108. [DOI: 10.1002/chem.202000045] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 02/03/2020] [Indexed: 12/28/2022]
Affiliation(s)
- Mianli Bian
- School of Pharmacy Nanjing University of Chinese Medicine Nanjing 210023 P. R. China
| | - Ying Sun
- School of Pharmacy Nanjing University of Chinese Medicine Nanjing 210023 P. R. China
| | - Yuanhao Liu
- School of Pharmacy Nanjing University of Chinese Medicine Nanjing 210023 P. R. China
| | - Zhongren Xu
- School of Pharmacy Nanjing University of Chinese Medicine Nanjing 210023 P. R. China
| | - Rong Fan
- School of Pharmacy Nanjing University of Chinese Medicine Nanjing 210023 P. R. China
| | - Ziwen Liu
- School of Pharmacy Nanjing University of Chinese Medicine Nanjing 210023 P. R. China
| | - Wukun Liu
- School of Pharmacy Nanjing University of Chinese Medicine Nanjing 210023 P. R. China
- State Key Laboratory of Natural Medicines China Pharmaceutical University Nanjing 210009 P. R. China
- State Key Laboratory of Coordination Chemistry Nanjing University Nanjing 210023 P. R. China
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Taniguchi H, Yamaguchi H, Dotsu Y, Shimada M, Gyotoku H, Senju H, Takemoto S, Kitazaki T, Fukuda M, Ogawara D, Soda H, Nakatomi K, Sugasaki N, Kinoshita A, Nagashima S, Ikeda T, Nakamura Y, Sakamoto N, Obase Y, Fukuda M, Mukae H. Phase II study of nedaplatin and amrubicin as first-line treatment for advanced squamous cell lung cancer. Thorac Cancer 2019; 10:1764-1769. [PMID: 31309738 PMCID: PMC6718021 DOI: 10.1111/1759-7714.13134] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 06/13/2019] [Accepted: 06/15/2019] [Indexed: 11/29/2022] Open
Abstract
Background The first‐line treatment for squamous cell lung cancer (SCC) has not necessarily been established; however, our previous exploratory study suggested that the combination of nedaplatin and amrubicin would be a promising treatment approach for patients with SCC. Therefore, a phase II study of this chemotherapeutic combination was designed to evaluate its efficacy and safety for treatment‐naïve patients with advanced SCC. Methods A total of 21 treatment‐naïve patients with stage IIIB/IV or postoperative recurrent SCC were enrolled from six institutions. Nedaplatin (100 mg/m2) on day 1 and amrubicin (25 mg/m2) on days 1–3 were administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR), while the secondary endpoints included overall survival (OS), progression‐free survival (PFS), and drug toxicities. Results Partial response was observed in seven of 21 cases (ORR, 33.3%; 95% confidence interval [CI], 14.5–52.2). Disease control rate, which includes stable disease, was 71.4%. Median OS and PFS was 14.6 and 4.1 months, respectively. This regimen did not cause any treatment‐related deaths. Grade 3/4 neutropenia developed in 8 of 21 cases (38.1%); however, febrile neutropenia developed in only 9.5% of the cases. Grade 3/4 gastrointestinal or neuromuscular toxicities were not observed. Conclusion The efficacy of the combination of nedaplatin and amrubicin was comparable to that of other conventional chemotherapeutic regimens for treatment‐naïve patients with advanced SCC, and no severe gastrointestinal or neuromuscular toxicities were observed. This combination therapy may be an alternative treatment approach, particularly in patients who cannot tolerate gastrointestinal or neuromuscular toxicities.
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Affiliation(s)
- Hirokazu Taniguchi
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hiroyuki Yamaguchi
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Yosuke Dotsu
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Midori Shimada
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hiroshi Gyotoku
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hiroaki Senju
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Shinnosuke Takemoto
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takeshi Kitazaki
- Department of Respiratory Medicine, The Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Masaaki Fukuda
- Department of Respiratory Medicine, The Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Daiki Ogawara
- Department of Respiratory Medicine, Sasebo City General Hospital, Sasebo, Japan
| | - Hiroshi Soda
- Department of Respiratory Medicine, Sasebo City General Hospital, Sasebo, Japan
| | - Katsumi Nakatomi
- Department of Respiratory Medicine, Ureshino Medical Center, Ureshino, Japan
| | - Nanae Sugasaki
- Department of Respiratory Medicine, Nagasaki Prefecture Shimabara Hospital, Shimabara, Japan
| | - Akitoshi Kinoshita
- Department of Respiratory Medicine, Nagasaki Prefecture Shimabara Hospital, Shimabara, Japan
| | - Seiji Nagashima
- Department of Respiratory Medicine, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan
| | - Takaya Ikeda
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Yoichi Nakamura
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Division of Thoracic Oncology, Tochigi Cancer Center, Utsunomiya, Japan
| | - Noriho Sakamoto
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Yasushi Obase
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Minoru Fukuda
- Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan
| | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Watanabe A, Katada C, Komori S, Moriya H, Yamashita K, Harada H, Azuma M, Kondo Y, Kubota Y, Furue Y, Kawanishi N, Yamane S, Wada T, Yano T, Ishido K, Tanabe S, Hayakawa K, Koizumi W. Feasibility of definitive chemoradiation therapy with nedaplatin and 5-fluorouracil in elderly patients with esophageal squamous cell carcinoma: A retrospective study. Adv Radiat Oncol 2018; 3:305-313. [PMID: 30197939 PMCID: PMC6127966 DOI: 10.1016/j.adro.2018.02.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Revised: 01/23/2018] [Accepted: 02/20/2018] [Indexed: 11/29/2022] Open
Abstract
PURPOSE This study was designed to retrospectively analyze the safety and efficacy of chemoradiation therapy with nedaplatin and 5-fluorouracil in elderly patients with esophageal squamous cell carcinoma. METHODS AND MATERIALS Eligible patients were aged 76 years or older, had a histopathologic diagnosis of esophageal squamous cell carcinoma, and were treated at the Kitasato University Hospital between January 2010 and March 2016. Chemotherapy consisted of nedaplatin in an intravenous dose of 90 mg/m2 on day 1 and 5-fluorouracil in an intravenous dose of 800 mg/m2 on days 1 to 5, repeated every 4 weeks for 2 cycles. Radiation therapy consisted of 50.4 Gy in 28 fractions for thoracic tumors and 61.2 Gy for cervical tumors. RESULTS Twenty-five patients were studied. Patient characteristics were as follows: median age 79 years (range, 76-85 years), clinical stage I/II/III/IV (7/8/8/2, respectively), and surgically resectable/unresectable (17/8, respectively). The completion rates of radiation therapy and chemoradiation therapy were 100% and 84%, respectively. Grade ≥3 acute toxicities included neutropenia (76%), leukopenia (72%), thrombocytopenia (32%), anemia (28%), anorexia (32%), oral mucositis (20%), febrile neutropenia (12%), and esophagitis (8%). Grade ≥3 late toxicities included esophageal stenosis (12%) and pleural effusion (4%). The complete response rate was 64%. In the median follow-up period of 18.9 months, the 1-year overall survival rate was 68%. CONCLUSIONS Definitive chemoradiation therapy with nedaplatin and 5-fluorouracil may be a feasible treatment option for elderly patients with esophageal squamous cell carcinoma.
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Affiliation(s)
- Akinori Watanabe
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Chikatoshi Katada
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Shouko Komori
- Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Hiromitsu Moriya
- Department of Gastrointestinal Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - Keishi Yamashita
- Department of Gastrointestinal Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - Hiroki Harada
- Department of Gastrointestinal Surgery, Kitasato University School of Medicine, Sagamihara, Japan
| | - Mizutomo Azuma
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Yuki Kondo
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Yo Kubota
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Yasuaki Furue
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Natsuko Kawanishi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Sakiko Yamane
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Takuya Wada
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Takafumi Yano
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Kenji Ishido
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Satoshi Tanabe
- Research and Development Center for New Frontier, Kitasato University School of Medicine, Sagamihara, Japan
| | - Kazushige Hayakawa
- Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Wasaburo Koizumi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
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Fahmy SA, Ponte F, Abd El-Rahman MK, Russo N, Sicilia E, Shoeib T. Investigation of the host-guest complexation between 4-sulfocalix[4]arene and nedaplatin for potential use in drug delivery. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2018; 193:528-536. [PMID: 29306207 DOI: 10.1016/j.saa.2017.12.070] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Revised: 12/10/2017] [Accepted: 12/26/2017] [Indexed: 05/28/2023]
Affiliation(s)
- Sherif Ashraf Fahmy
- Department of Chemistry, The American University in Cairo, New Cairo 11835, Egypt
| | - Fortuna Ponte
- Department of Chemistry and Chemical Technologies, University of Calabria, Arcavacata di Rende, 87036, Italy
| | - Mohamed K Abd El-Rahman
- Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr-El Aini Street, Cairo, Egypt 11562
| | - Nino Russo
- Department of Chemistry and Chemical Technologies, University of Calabria, Arcavacata di Rende, 87036, Italy; Division de Ciencias Basicas e Ingenieria, Departamento de Quimica, Universidad, Autonoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco No. 186, Col. Vicentina, CP 09340 Mexico, Distrito Federal, Mexico
| | - Emilia Sicilia
- Department of Chemistry and Chemical Technologies, University of Calabria, Arcavacata di Rende, 87036, Italy.
| | - Tamer Shoeib
- Department of Chemistry, The American University in Cairo, New Cairo 11835, Egypt.
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Paclitaxel plus nedaplatin vs. paclitaxel plus carboplatin in women with epithelial ovarian cancer: A multi-center, randomized, open-label, phase III trial. Oncol Lett 2018; 15:3646-3652. [PMID: 29467885 PMCID: PMC5796383 DOI: 10.3892/ol.2018.7761] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Accepted: 09/13/2017] [Indexed: 11/05/2022] Open
Abstract
The multi-center, randomized, open-label, phase III trial discussed in the present study was performed to compare the clinical outcomes of nedaplatin (NDP) plus paclitaxel, and carboplatin (CBP) plus paclitaxel for the treatment of epithelial ovarian cancer (EOC). In the current study, 182 patients with International Federation of Gynecology and Obstetrics (FIGO) stage II-IV EOC were randomly assigned to receive NDP plus paclitaxel or CBP plus paclitaxel at 3-week intervals for a total of six courses. The primary endpoints were progression-free survival rate (PFS) and overall survival rate (OS). The secondary endpoints were toxicity profiles. The median follow-up was 44.63 months [95% confidence interval (CI) 33.67-46.47 months] for the NDP group and 47.63 months (95% CI 45.13-49.07 months) for the CBP group. Overall, there was no significant difference in PFS or OS between the two groups (P=0.09 for PFS, and P=0.65 for OS). For the patients with FIGO stage III-IV EOC, the NDP plus paclitaxel regimen significantly prolonged PFS (P=0.02) but did not result in improved OS (P=0.53) when compared with the CBP group. The patients in the NDP plus paclitaxel group also exhibited a lower incidence rate of grade 3 or 4 leucopenia (P=0.03). Other hematological and non-hematological toxicity profiles were similar between the two groups. Compared with CBP plus paclitaxel regimens, NDP plus paclitaxel regimens achieved comparable survival outcomes and similar toxicity profiles. However, patients of FIGO stage III-IV EOC may experience more clinical benefits from NDP plus paclitaxel treatment, including a prolonged PFS and a lower incidence rate of leucopenia. Therefore, an NDP-based regimen may be an alternative choice when using platinum-based agents to treat EOC.
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Yoshida H, Shintani D, Ogasawara A, Fujiwara K. Feasibility and response to nedaplatin monotherapy in older patients with ovarian cancer. Arch Gynecol Obstet 2017; 296:819-826. [PMID: 28803267 DOI: 10.1007/s00404-017-4487-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Accepted: 08/07/2017] [Indexed: 11/28/2022]
Abstract
PURPOSE Nedaplatin (NDP), a second-generation platinum analog, has been developed to reduce the toxicity of cisplatin. Although the use of NDP for older patients seems suitable because of the reduced risk of toxicity, few studies have investigated its application to older patients with ovarian cancer (OC). The objective of this study was to compare the tolerability and effectiveness of NDP between patients older and younger than 70 years of age with OC. METHODS We enrolled 56 patients with OC who were treated with NDP monotherapy and divided them into those who were 70 years and older (n = 18) and younger than 70 years (n = 38). NDP was administered intravenously until disease progression or unacceptable toxicities occurred. RESULTS The incidences of grade 3/4 hematological toxicities were significantly higher in the older patients than in the younger patients, including anemia (p = 0.0021), leucopenia (p = 0.029), neutropenia (p = 0.0048), and thrombocytopenia (p = 0.0024). The incidence of elevated creatinine was also significantly higher in the older patients (p = 0.0063). Older patients had significantly more frequent dose reductions (p = 0.017) and treatment interruptions from toxicity (p = 0.04). The tumor response rate for NDP did not differ significantly between younger (29%) and older (28%) patients (p = 0.47). The two age groups also did not significantly differ in progression-free survival (p = 0.27) and overall survival (p = 0.46). CONCLUSIONS Although NDP is a useful therapeutic option for OC, careful consideration of the adverse effect should be given for patients 70 years and older.
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Affiliation(s)
- Hiroyuki Yoshida
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.
| | - Daisuke Shintani
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
| | - Aiko Ogasawara
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
| | - Keiichi Fujiwara
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan
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Peng PJ, Lv BJ, Wang ZH, Liao H, Liu YM, Lin Z, Con YY, Huang PY. Multi-institutional prospective study of nedaplatin plus S-1 chemotherapy in recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-containing regimens. Ther Adv Med Oncol 2016; 9:68-74. [PMID: 28203299 DOI: 10.1177/1758834016675099] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND In this multi-institutional prospective study, we aimed to assess the safety and efficacy of nedaplatin plus S-1 (NS) chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma (NPC) when platinum-containing regimens failed. METHODS A total of 52 recurrent and metastatic NPC patients who previously received, but failed with platinum-containing chemotherapy, had oral S-1 chemotherapy (twice daily from the first day to the fourteenth day) and nedaplatin (80 mg/ m2, day 1) every 3 weeks. The body surface area (BSA) decided the dose of S-1: 40 mg twice a day when BSA < 1.25 m2; 50 mg twice daily when 1.25 m2 ⩽ BSA < 1.5 m2; and 60 mg twice daily when BSA ⩾ 1.5 m2. RESULTS Treatment was well tolerated. The main hematological adverse event was neutropenia. Five patients (9.6%) had grade 3 neutropenia. Three patients were found with grade 3 anemia (5.8%). One patient was found with grade 3 thrombocytopenia (1.9%). No patient was found with grade 3 or 4 nonhematological toxicity. The rates of complete response, partial response and overall response were 3.8%, 38.5% and 42.3%, respectively. Median time to progression was 6.2 months and median survival was 14.6 months. The rates of 1-year survival and 2-year survival were 63% and 27%, respectively. CONCLUSIONS NS chemotherapy provides a satisfactory and safe clinical activity for patients with recurrent and metastatic NPC after platinum-containing chemotherapy failed.
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Affiliation(s)
- Pei-Jian Peng
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Province, People's Republic of China
| | - Bao-Jun Lv
- Department of Surgical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhu Hai, Guangdong Province, China
| | - Zhi-Hui Wang
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Province, People's Republic of China
| | - Hai Liao
- Department of Medical Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Yu-Meng Liu
- Department of Oncology, the People's Hospital of Zhongshan City, Zhongshan, Guangdong Province, China
| | - Zhong Lin
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Province, People's Republic of China
| | - Yun-Yan Con
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong Province, People's Republic of China
| | - Pei-Yu Huang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of nasopharyngeal carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, China
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Pang H, Feng T, Lu H, Meng Q, Chen X, Shen Q, Dong X, Cai L. Efficacy and Safety of Nedaplatin in Advanced Breast Cancer Therapy. Cancer Invest 2016; 34:167-72. [PMID: 27057601 DOI: 10.3109/07357907.2016.1144061] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE To compare the time-to-treatment failure (TTF), overall survival (OS), overall response rate (ORR), and adverse effects of regimens including nedaplatin- or cisplatin-based chemotherapy for advanced breast cancer (ABC). METHODS A total of 171 patients with ABC (admission between July 2008 and July 2013) were retrospectively analyzed. Patients received either nedaplatin 75 mg/m(2) (arm N; n = 85) or cisplatin 75 mg/m(2) (arm C; n = 86) in combination with other second-generation chemotherapeutic drugs, such as paclitaxel 175 mg/m(2), docetaxel 75 mg/m(2), gemcitabine 1.25 g/m(2), and navelbine 25 mg/m(2) every 21 days (nedaplatin, cisplatin, paclitaxel, docetaxel on day 1; gemcitabine, navelbine on days 1 and 8). The primary endpoint was TTF in each arm; secondary endpoints were OS, ORR, and toxicity. RESULTS In the assessable patient population, in arm N, median TTF and OS was 13.87 months (95% CI: 11.55-16.19) and 31.53 months (95% CI: 28.42-34.64), respectively, with an ORR of 48.2%. In arm C, median TTF and OS was 8.7 months (95% CI: 5.82-11.59) and 24.87 months (95% CI: 18.98-30.75), respectively, with an ORR of 37.2%. The occurrence of grades 3 and 4 hematologic toxicity was more frequent (45.9% vs. 25.6%, p = 0.003) in arm N than in arm C. However, grade ≥2 nonhematologic toxicity was less frequent in arm N than in arm C (12.9% vs. 46.5%, p = 2.05 × 10(-7)). CONCLUSIONS Nedaplatin-based chemotherapy regimen was well tolerated and efficiently improved patients' quality of life characterized by prolonged TTF and OS, with a marginal ORR.
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Affiliation(s)
- Hui Pang
- a Department of Internal Medical Oncology , Harbin Medical University Cancer Hospital , Harbin , China
| | - Ting Feng
- a Department of Internal Medical Oncology , Harbin Medical University Cancer Hospital , Harbin , China
| | - Hailing Lu
- a Department of Internal Medical Oncology , Harbin Medical University Cancer Hospital , Harbin , China
| | - Qingwei Meng
- a Department of Internal Medical Oncology , Harbin Medical University Cancer Hospital , Harbin , China
| | - Xuesong Chen
- a Department of Internal Medical Oncology , Harbin Medical University Cancer Hospital , Harbin , China
| | - Qiang Shen
- b Department of Clinical Cancer Prevention , The University of Texas MD Anderson Cancer Center , Houston , Texas , USA
| | - Xiaoqun Dong
- c College of Medicine, The University of Oklahoma Health Sciences Center , Oklahoma City , Oklahoma , USA
| | - Li Cai
- a Department of Internal Medical Oncology , Harbin Medical University Cancer Hospital , Harbin , China
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Peng PJ, Lv BJ, Tang C, Liao H, Lin Z, Liu YM, Wang ZH, Wang SY, Cheng ZB. Phase II trial of docetaxel combined with nedaplatin for patients with recurrent and metastatic nasopharyngeal carcinoma. DRUG DESIGN DEVELOPMENT AND THERAPY 2015; 9:6401-5. [PMID: 26677316 PMCID: PMC4677648 DOI: 10.2147/dddt.s95946] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Purpose This Phase II trial was designed to evaluate the efficacy and safety of docetaxel combined with nedaplatin as first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma. Methods In this multicenter Phase II trial, the patients were treated with intravenous docetaxel (75 mg/m2, day 1) and nedaplatin (80 mg/m2, day 1), each cycle repeated every 3 weeks for two cycles at least. Results From January 2010 to November 2013, a total of 78 patients were recruited in this trial. Among them, 73 patients were assessable for response. The treatment was well tolerated. The main hematological adverse event was neutropenia. A total of 12 patients (15.4%) had grade 3 or grade 4 neutropenia. Grade 3 anemia was observed in six patients (7.7%) and no grade 3/4 thrombocytopenia was observed. No Grade 3/4 non-hematological toxicity was observed. There were five complete response (6.8%), 43 partial responses (58.9%), and the overall response rate was 65.8% (95% confidence interval [CI], 48.7%–81.2%). With a median follow-up period of 18.6 months, the median time to progression was 7.9 months (95% CI, 4.2–10.8 months), median overall survival was 15.7 months (95% CI, 11.6–18.5 months). Conclusion Docetaxel combined with nedaplatin offers a satisfactory clinical activity and an acceptable safety profile as first-line chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma.
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Affiliation(s)
- Pei-Jian Peng
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Bao-Jun Lv
- Department of Surgical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Con Tang
- Department of Surgical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Hai Liao
- Department of Medical Oncology, Cancer Centre, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Zhong Lin
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Yu-Meng Liu
- Department of Oncology, People's Hospital of Zhongshan City, Zhongshan, People's Republic of China
| | - Zhi-Hui Wang
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China
| | - Si-Yang Wang
- Department of Radiation Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, People's Republic of China
| | - Zhi-Bin Cheng
- Department of Radiation Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, People's Republic of China
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Murakami Y, Tabata KI, Sugita A, Mochizuki K, Maeyama R, Okazaki M, Nishi M, Matsumoto K, Fujita T, Satoh T, Jiang SX, Saegusa M, Iwamura M. Multidisciplinary treatment including systemic chemotherapy for a malignant phyllodes tumour of the prostate. Can Urol Assoc J 2014; 8:E263-5. [PMID: 24839496 DOI: 10.5489/cuaj.1648] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
A 22-year-old man was referred to our hospital with macroscopic hematuria and consistent anal pain. Magnetic resonance imaging revealed an enlarged prostate tumour invading the bladder and rectum. A biopsy revealed an unclassified spindle cell sarcoma. Subsequently, radical cystoprostatectomy and resection of the rectum were performed. A histopathological examination revealed a prostatic malignant phyllodes tumour with a negative surgical margin. However, a local recurrence was identified 2 months after surgery. Induction therapy included 4 cycles of systemic chemotherapy comprising etoposide with ifosfamide and cisplatin. Although a partial response was observed at the local site, lung metastasis developed. Second-line chemotherapy with ifosfamide and doxorubicin with radiotherapy to the pelvis was administered and led to complete regression; however, its efficacy was transient. Although additional chemotherapy was administered, the patient eventually died due to the rapidly growing, recurrent tumour.
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Affiliation(s)
- Yasukiyo Murakami
- Department of Urology, Kitasato University School of Medicine, Japan
| | - Ken-Ichi Tabata
- Department of Urology, Kitasato University School of Medicine, Japan
| | - Atsushi Sugita
- Department of Urology, Kitasato University School of Medicine, Japan
| | - Kohei Mochizuki
- Department of Urology, Kitasato University School of Medicine, Japan
| | - Ryota Maeyama
- Department of Urology, Kitasato University School of Medicine, Japan
| | - Miyoko Okazaki
- Department of Pharmacology, Kitasato University School of Medicine, Japan
| | - Morihiro Nishi
- Department of Urology, Kitasato University School of Medicine, Japan
| | | | - Tetsuo Fujita
- Department of Urology, Kitasato University School of Medicine, Japan
| | - Takefumi Satoh
- Department of Urology, Kitasato University School of Medicine, Japan
| | - Shi-Xu Jiang
- Department of Pathology, Kitasato University School of Medicine, Japan
| | - Makoto Saegusa
- Department of Pathology, Kitasato University School of Medicine, Japan
| | - Masatsugu Iwamura
- Department of Urology, Kitasato University School of Medicine, Japan
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He YF, Ji CS, Hu B, Fan PS, Hu CL, Jiang FS, Chen J, Zhu L, Yao YW, Wang W. A phase II study of paclitaxel and nedaplatin as front-line chemotherapy in Chinese patients with metastatic esophageal squamous cell carcinoma. World J Gastroenterol 2013; 19:5910-5916. [PMID: 24124338 PMCID: PMC3793146 DOI: 10.3748/wjg.v19.i35.5910] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2013] [Revised: 08/01/2013] [Accepted: 08/13/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy and safety of paclitaxel-nedaplatin combination as a front-line regimen in Chinese patients with metastatic esophageal squamous cell carcinoma (ESCC).
METHODS: A two-center, open-label, single-arm phase II study was designed. Thirty-nine patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. Patients received 175 mg/m2 of paclitaxel over a 3 h infusion on 1 d, followed by nedaplatin 80 mg/m2 in a 1 h infusion on 2 d every 3 wk until the documented disease progression, unacceptable toxicity or patient’s refusal.
RESULTS: Of the 36 patients assessable for efficacy, there were 2 patients (5.1%) with complete response and 16 patients (41.0%) with partial response, giving an overall response rate of 46.1%. The median progression-free survival and median overall survival for all patients were 7.1 mo (95%CI: 4.6-9.7) and 12.4 mo (95%CI: 9.5-15.3), respectively. Toxicities were moderate and manageable. Grade 3/4 toxicities included neutropenia (15.4%), nausea (10.3%), anemia (7.7%), thrombocytopenia (5.1%), vomiting (5.1%) and neutropenia fever (2.6%).
CONCLUSION: The combination of paclitaxel and nedaplatin is active and well tolerated as a first-line therapy for patients with metastatic ESCC.
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Yoshiike F, Koizumi T, Kitaguchi Y, Hatayama O, Yasuo M, Sasabayashi M, Wakamatsu H, Fujimoto K, Kubo K. Phase I Trial of Nedaplatin and Paclitaxel for Patients with Non-Small Cell Lung Cancer. J Chemother 2013; 17:550-4. [PMID: 16323445 DOI: 10.1179/joc.2005.17.5.550] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
A phase I study was conducted to evaluate the maximum tolerated dose and feasibility of combination with nedaplatin (NDP) and paclitaxel in patients with non-small cell lung cancer (NSCLC). Fifteen patients under 75 years old, with unresectable NSCLC who had not previously received chemotherapy or radiotherapy, with a performance status of 0-1, were enrolled. The dose escalation levels (NDP/Paclitaxel; mg/m2 day 1) were 80/150 (level 1), 80/180 (level 2), 90/180 (level 3) and repeated every 28 days. All patients receiving level 3 had dose-limiting toxicity. One patient developed grade 4 neutropenia with infection, two had incomplete recovery of neutropenia and thrombocytopenia by the 28th day after the first cycle of chemotherapy. Non-hematologic toxicities, including nephrotoxicity, nausea/vomiting, alopecia, and hypersensitivity reaction, were tolerated. Three of the 15 patients achieved partial responses. We concluded that the recommended dose was paclitaxel 180 and NDP 80 mg/m2 due to the hematologic toxicity.
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Affiliation(s)
- F Yoshiike
- First Department of Internal Medicine, Shinshu University School of Medicine, Japan
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16
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Peng PJ, Ou XQ, Chen ZB, Liao H, Peng YL, Wang SY, Zhang HY, Lin Z. Multicenter phase II study of capecitabine combined with nedaplatin for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy. Cancer Chemother Pharmacol 2013; 72:323-8. [PMID: 23728706 DOI: 10.1007/s00280-013-2203-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Accepted: 05/22/2013] [Indexed: 12/27/2022]
Abstract
PURPOSE There is no standard second-line regimen for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy. A multicenter phase II study was conducted to evaluate the efficacy and toxicity of capecitabine combined with nedaplatin for these patients. PATIENTS AND METHODS In the multicenter, open-label, single-arm phase II study, patients with recurrent and metastatic nasopharyngeal carcinoma who failed to previous cisplatin-based chemotherapy were enrolled. Patients received oral capecitabine (1,000 mg/m(2) twice daily from day 1 to 14) and intravenous nedaplatin (80 mg/m(2), day 1) every 3 weeks for two cycles at least. RESULTS A total of forty-eight patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. Treatment was well tolerated. Grade 3/4 toxicities included neutropenia (8.4 %), anemia (2.1 %), diarrhea (4.2 %), stomatitis (6.3 %), and hand-foot syndrome (HFS) (4.2 %). There were two complete response (4.2 %), eighteen partial responses (37.5 %), giving an overall response rate of 41.7 % [95 % confidence interval (CI) 27.7-55.8]. With a median follow-up period of 12.1 months, the median time to progression was 5.8 months (95 % CI 3.9-7.8 months) and median overall survival was 12.4 months (95 % CI 9.6-16.8 months). CONCLUSION Capecitabine combined with nedaplatin offers a satisfactory clinical activity and an acceptable safety profile for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy.
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Affiliation(s)
- Pei-Jian Peng
- Department of Medical Oncology, The Fifth Affiliated Hospital of Sun-Yat-Sen University, 52 Mei Hua Road East, Zhu Hai, Guangdong Province, People's Republic of China.
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17
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Michikami H, Minaguchi T, Ochi H, Onuki M, Okada S, Matsumoto K, Satoh T, Oki A, Yoshikawa H. Safety and efficacy of substituting nedaplatin after carboplatin hypersensitivity reactions in gynecologic malignancies. J Obstet Gynaecol Res 2012; 39:330-5. [DOI: 10.1111/j.1447-0756.2012.01893.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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18
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Yin M, Zhang H, Li H, Li X, Liu Y, Chen X, Lou G, Li K. The toxicity and long-term efficacy of nedaplatin and paclitaxel treatment as neoadjuvant chemotherapy for locally advanced cervical cancer. J Surg Oncol 2011; 105:206-11. [DOI: 10.1002/jso.22052] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2011] [Accepted: 07/08/2011] [Indexed: 11/07/2022]
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19
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Goto T, Takano M, Ohishi R, Iwasa N, Shimizu M, Hasegawa K, Nagao S, Fujiwara K. Single nedaplatin treatment as salvage chemotherapy for platinum/taxane-resistant/refractory epithelial ovarian, tubal and peritoneal cancers. J Obstet Gynaecol Res 2010; 36:764-8. [DOI: 10.1111/j.1447-0756.2010.01217.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Investigation on pharmacokinetics, tissue distribution and excretion of a novel anticancer platinum compound by inductively coupled plasma mass spectrometry after intravenous administration to rats. Arch Pharm Res 2009; 32:1621-8. [DOI: 10.1007/s12272-009-2116-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2009] [Revised: 09/09/2009] [Accepted: 09/17/2009] [Indexed: 10/20/2022]
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Second-line combination chemotherapy with docetaxel and nedaplatin for Cisplatin-pretreated refractory metastatic/recurrent esophageal squamous cell carcinoma. J Thorac Oncol 2009; 4:1017-21. [PMID: 19542899 DOI: 10.1097/jto.0b013e3181add9c7] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND There is an urgent need for an effective second-line chemotherapy regimen after failure of the standard cisplatin and 5-fluorouracil therapy. PATIENTS AND METHODS This study investigated the efficacy and toxicity of the combination of docetaxel (30 mg/m2) during a 1-hour infusion, followed by nedaplatin (50 mg/m2) during a 2-hour infusion (both drugs were administered on day 1 as an outpatient regimen and repeated every 2 weeks) as second-line chemotherapy for patients with cisplatin-pretreated refractory metastatic/recurrent esophageal squamous cell carcinoma after surgery. RESULTS Forty-six of the 48 patients (95.8%) were assessable for response. Partial response was confirmed in 13 of 48 cases yielding a response rate of 27.1% (95% confidence interval [CI], 14.5-39.7%). The median overall time to progression and overall survival was 3.1 months (95% CI, 2.3-3.9 months) and 5.9 months (95% CI, 3.9-7.8 months), respectively. The estimate of overall survival at 12 months was 16.7% (95% CI, 6.1-27.2%). Grade 3 anemia leucopenia, grade 4 anemia leucopenia and neutropenia were detected in only 4 (8.7%), 8 (17.4%), and 9 patients (19.6%), respectively. CONCLUSIONS The combination chemotherapy of docetaxel and nedaplatin in the outpatient setting is well tolerated and useful as second-line chemotherapy for cisplatin-pretreated refractory metastatic/recurrent esophageal squamous cell carcinoma.
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Kurita H, Yamamoto E, Nozaki S, Wada S, Furuta I, Miyata M, Kurashina K. Multicenter phase 2 study of induction chemotherapy with docetaxel and nedaplatin for oral squamous cell carcinoma. Cancer Chemother Pharmacol 2009; 65:503-8. [PMID: 19579024 DOI: 10.1007/s00280-009-1056-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2009] [Accepted: 06/16/2009] [Indexed: 10/20/2022]
Abstract
PURPOSE To determine the clinical and hisotological efficacy and toxicities of induction chemotherapy with docetaxel (DOC) and nedaplatin (CDGP) for oral squamous cell carcinoma (OSCC) in the preoperative setting. METHODS A total of 30 patients with locally advanced but operable OSCC were enrolled. Combination induction chemotherapy consisted of DOC 60 mg/m2 followed by CDGP 100 mg/m2. RESULTS All patients received one cycle of chemotherapy. In the clinical assessment, ten patients achieved partial response for an overall response rate of 33.3% (95% CI, 16.4-50.2%). Histological assessment of surgical specimens showed an overall response rate of 56.6% (95% CI, 38.9-74.3%). Although severe neutropenia was observed in 90% of patients, only one patient (3.3%) experienced severe infection. Toxicities associated with this regimen did not interfere with planned radical surgery. CONCLUSIONS A single cycle of preoperative combination chemotherapy with DOC and CDGP showed moderate histological activity with an acceptable safety profile for the planned radical surgery. Further studies testing more cycles before surgery might be more appropriate.
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Affiliation(s)
- Hiroshi Kurita
- Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
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Cao W, Xu C, Lou G, Jiang J, Zhao S, Geng M, Xi W, Li H, Jin Y. A phase II study of paclitaxel and nedaplatin as first-line chemotherapy in patients with advanced esophageal cancer. Jpn J Clin Oncol 2009; 39:582-7. [PMID: 19509000 DOI: 10.1093/jjco/hyp058] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE The aim of this study was to assess the efficacy and toxicity of the combination of paclitaxel and nedaplatin as a first-line chemotherapy for patients with advanced esophageal cancer. METHODS Patients with advanced esophageal cancer received 175 mg/m(2) of paclitaxel over a 3 h infusion, followed by nedaplatin 80 mg/m(2) in a 1 h infusion on day 1 every 3 weeks until the documented disease progression, unacceptable toxicity or patient's refusal. RESULTS Between March 2005 and December 2007, 48 patients entered in the study. Forty-six (95.8%) of the 48 patients were assessable for response. The overall response rate was 41.7% (95% CI, 27.8-55.7%) with 2 complete responses and 18 partial responses. The median follow-up period was 20.5 months (range, 12.5-27.2 months). The median overall time to progression and overall survival (OS) were 6.1 months (95% CI, 4.8-7.4 months) and 11.5 months (95% CI, 9.1-13.9 months), respectively. The estimate of OS at 12 and 24 months was 43.8% (95% CI, 29.7-77.8%) and 10.4% (95% CI, 1.8-19.1%), respectively. Most patients experienced anemia, during their course of therapy with 6 (13.0%) patients for grade 3/4 anemia, and grade 1 or 2 anemia was detected in 23 (50%) patients. Grade 3 leucopenia, neutropenia and thrombocytopenia were documented in 8 (17.4%), 9 (17.4%) and 2 (4.3%) patients, respectively. Grade 3 nausea and vomiting were detected in 3 (6.5%) and 2 (4.3%) patients, respectively. Two patients (4.3%) were hospitalized because of treatment-related complications. The treatment was well tolerated and no toxic death occurred. CONCLUSIONS Combination of paclitaxel and nedaplatin is a tolerated treatment modality with promising activity in previously untreated advanced esophageal cancer.
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Affiliation(s)
- Weiguo Cao
- Department of Oncology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Rui Jin Er Lu, Shanghai 200025, PR China
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Phase II evaluation of nedaplatin and paclitaxel in patients with metastatic esophageal carcinoma. Cancer Chemother Pharmacol 2008; 64:327-33. [PMID: 19048253 DOI: 10.1007/s00280-008-0874-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2008] [Accepted: 11/07/2008] [Indexed: 02/05/2023]
Abstract
PURPOSE To evaluate the efficiency and toxicities of nedaplatin and paclitaxel in patients with metastatic carcinoma of the esophagus. METHODS Thirty-nine untreated patients with confirmed metastatic tumors were enrolled. Patients were treated with nedaplatin 80 mg/m(2) and paclitaxel 175 mg/m(2) on day 1. Treatment was repeated every 21 days. RESULTS Thirty-six patients were eligible to be evaluated to have had a response. The overall response rate was 43.6% (17/39), with complete response and partial response rates of 2.6 and 41%, respectively. The median progression-free survival and overall survival time was 6.1 and 10.3 months, respectively. Grade 3/4 toxicities were only observed in six patients [neutropenia in three patients (7.7%) and nausea/vomiting in three patients (7.7%)]. CONCLUSION Comparing to other regimens, combination of nedaplatin and paclitaxel achieved an encouraging clinical outcome, with relatively minimal toxicities for patients with metastatic esophageal carcinoma.
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Su Q, Liu Q, Luo G, Liu W, Yu Y, Wang Y, Bi K. Pharmacokinetic Investigation on a Novel Antitumour Platinum Compound in Rabbit Plasma by Inductively Coupled Plasma Mass Spectrometry After Intravenous Administration. Drug Dev Ind Pharm 2008; 34:472-7. [DOI: 10.1080/03639040701662560] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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Kanai M, Matsumoto S, Nishimura T, Shimada Y, Watanabe G, Kitano T, Misawa A, Ishiguro H, Yoshikawa K, Yanagihara K, Teramukai S, Mitsumori M, Chiba T, Sakai Y, Fukushima M. Retrospective analysis of 27 consecutive patients treated with docetaxel/nedaplatin combination therapy as a second-line regimen for advanced esophageal cancer. Int J Clin Oncol 2007; 12:224-7. [PMID: 17566847 DOI: 10.1007/s10147-007-0666-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2006] [Accepted: 02/02/2007] [Indexed: 12/23/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the efficacy and safety of combination therapy with docetaxel and nedaplatin in advanced esophageal cancer as a second-line regimen in an outpatient setting. METHODS Twenty-seven consecutive patients with advanced esophageal cancer who received docetaxel/nedaplatin combination therapy as a second-line regimen were retrospectively evaluated. The combination therapy consisted of intravenous administration of docetaxel 30 mg/m(2) and nedaplatin 40 mg/m(2) every 2 weeks. RESULTS The patients received a median of 7.4 cycles of treatment (range, 2-25 cycles ). No complete response was observed, and 3 of the 27 patients (11%) achieved partial responses. The disease control rate (partial response + stable disease) was 52%. The median survival time (MST) was 11.4 months. Severe hematological adverse events (grade 3-4) were: neutropenia (n = 10; 37%) and anemia (n = 5; 19%); there was neither febrile neutropenia nor grade 3-4 thrombocytopenia. Furthermore, no severe nonhematological adverse events or treatment-related deaths were observed. CONCLUSION Combination therapy of docetaxel with nedaplatin was safe and well tolerated; however, the development of more effective therapy is warranted to improve the prognosis of esophageal cancer.
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Affiliation(s)
- Masashi Kanai
- Outpatient Oncology Unit, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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27
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Zöllinger M, Kelter G, Fiebig HH, Lindel T. Antitumor activity of the marine natural product dibromophakellstatin in vitro. Bioorg Med Chem Lett 2007; 17:346-9. [PMID: 17095216 DOI: 10.1016/j.bmcl.2006.10.046] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2006] [Revised: 10/17/2006] [Accepted: 10/20/2006] [Indexed: 10/24/2022]
Abstract
The pyrrole-imidazole alkaloid rac-dibromophakellstatin displayed selective antitumor activity in vitro when tested in 36 cell lines in a cell survival and proliferation assay. The ovarian cancer cell line OVXF 899L proved to be most sensitive (0.60 microM, IC50), followed by the glioblastoma cell line CNXF 498NL (0.93 microM), the non-small lung cancer cell line LXF 529L (0.96 microM), and the uterus cancer cell line UXF 1138L (1.21 microM). The selectivity profile of rac-dibromophakellstatin may be indicative for a novel mechanism of action. Separation of the enantiomers on a chiral HPLC column revealed that only the naturally occurring (-)-dibromophakellstatin is antitumor active. Debromination of the pyrrole moiety leads to complete loss of activity.
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Affiliation(s)
- Michael Zöllinger
- Ludwig Maximilian University, Department of Chemistry and Biochemistry, Butenandtstr. 5-13, 81377 Munich, Germany
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28
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Yoshioka T, Sakayori M, Kato S, Chiba N, Miyazaki S, Nemoto K, Shibata H, Shimodaira H, Ohtsuka K, Kakudo Y, Sakata Y, Ishioka C. Dose escalation study of docetaxel and nedaplatin in patients with relapsed or refractory squamous cell carcinoma of the esophagus pretreated using cisplatin, 5-fluorouracil, and radiation. Int J Clin Oncol 2006; 11:454-60. [PMID: 17180514 DOI: 10.1007/s10147-006-0610-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2005] [Accepted: 08/08/2006] [Indexed: 02/06/2023]
Abstract
BACKGROUND Definitive chemoradiation with cisplatin (CDDP) and 5-fluorouracil (5FU) has been playing an important role in the treatment of esophageal cancer, but some patients are not curable or have recurrent lesions. However, few chemotherapeutic regimens are available for such patients. Docetaxel and nedaplatin are active for esophageal cancer. We conducted a dose-escalation study of docetaxel and nedaplatin as second line-chemotherapy after definitive chemoradiation in patients with relapsed or refractory squamous cell carcinoma of the esophagus after chemoradiation. METHODS Nedaplatin was administered on day 1 and docetaxel was administered on days 1 and 15, every 4 weeks. Dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle. RESULTS Twelve patients were enrolled. At a docetaxel dose of 30 mg/m(2) and a nedaplatin dose of 80 mg/m(2), one grade 4 neutropenia occurred and caused one treatment break longer than 2 weeks, but there were few DLTs. At doses of 35 and 80 mg/m(2), respectively, two grade 4 neutropenias and one grade 2 thrombopenia occurred and caused three treatment breaks longer than 2 weeks. Therefore, the maximum tolerated dose was established at this dose level. Two grade 3 anorexias and one grade 3 nausea occurred, but other non-hematological toxicities were generally mild. Responses were seen in one-fourth of the 12 patients, including one complete remission. CONCLUSION The recommended doses of docetaxel and nedaplatin were 30 and 80 mg/m(2), respectively. This combination could be a potential second-line treatment for this target population.
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Affiliation(s)
- Takashi Yoshioka
- Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
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Osaka Y, Takagi Y, Hoshino S, Tachibana S, Tsuchida A, Aoki T. Combination chemotherapy with docetaxel and nedaplatin for recurrent esophageal cancer in an outpatient setting. Dis Esophagus 2006; 19:473-6. [PMID: 17069591 DOI: 10.1111/j.1442-2050.2006.00614.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The purpose of this study was to address the feasibility of combination chemotherapy of docetaxel and nedaplatin for recurrent esophageal cancer patients in an outpatient setting. Patients received docetaxel (30 mg/m(2) intravenously) on day 1 and nedaplatin (40 mg/m(2) intravenously) on day 1 every 2 weeks. In total, 28 patients with recurrent esophageal cancer after the initial treatment (esophagectomy, chemotherapy and/or chemoradiotherapy) were enrolled. Each patient received six cycles of treatment and was evaluated with a computed tomography scan. The percentage of patients who completed this therapy was 60.7%. Complete response and partial response were achieved by 3.6% and 35.7% of patients, respectively. The most frequent toxicities were leukopenia and anemia; non-hematological toxicities were generally mild. There was no treatment-related death. The median survival time and 1-year survival rate were 8.5 months and 15.9%, respectively. This outpatient combination chemotherapy was useful as second-line chemotherapy for recurrent esophageal cancer.
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Affiliation(s)
- Y Osaka
- Third Department of Surgery, Tokyo Medical University, Tokyo, Japan.
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Shinohara N, Harabayashi T, Suzuki S, Nagao K, Seki H, Murakumo M, Mitsuhashi K, Demura T, Nagamori S, Matsuyama H, Naito K, Nonomura K. Salvage chemotherapy with paclitaxel, ifosfamide, and nedaplatin in patients with urothelial cancer who had received prior cisplatin-based therapy. Cancer Chemother Pharmacol 2006; 58:402-7. [PMID: 16416335 DOI: 10.1007/s00280-005-0175-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2005] [Accepted: 12/14/2005] [Indexed: 11/25/2022]
Abstract
BACKGROUND AND AIMS The aim of the present phase II study was to evaluate the efficacy of combination chemotherapy of paclitaxel, ifosfamide, and nedaplatin (PIN regimen) in patients with recurrent urothelial cancer who had been treated with cisplatin-based chemotherapy. PATIENTS/METHODS Eligible patients were those with histologically confirmed urothelial cancer who had progressed or relapsed after cisplatin-based chemotherapy. The PIN regimen consisted of paclitaxel 175 mg/m(2) on day 1; ifosfamide 4.5 g/m2 divided over days 1, 2, and 3; and nedaplatin 70 mg/m(2) on day 1; PIN was given every 28 days. RESULTS Among the 32 patients enrolled in the study (median age, 66 years), complete and partial responses were obtained in 5 patients and 19 patients, respectively, with an overall response rate of 75% (95% confidence interval [CI], 59-91%). The median time to progression was 8 months (range, 0-50+ months) and the median survival was 22 months (range, 4-52+ months). The 1- and 2-year overall survival rates were 53.7 and 42.9%, respectively. All patients experienced Grade 3 or 4 neutropenia, while Grade 3 or 4 thrombocytopenia was seen in 8 patients; Grade 3 or 4 anemia was seen in 6 patients; Grade 3 neuropathy was observed in 1 patient, for whom the PIN therapy was discontinued. There were no treatment-related deaths. CONCLUSION The PIN combination was highly active and tolerable in previously treated patients with urothelial cancer as a second-line treatment.
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Affiliation(s)
- Nobuo Shinohara
- Department of Urology, Hokkaido University Graduate School of Medicine, Kitaku, Sapporo, Japan.
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Kawai Y, Taniuchi S, Okahara S, Nakamura M, Gemba M. Relationship between cisplatin or nedaplatin-induced nephrotoxicity and renal accumulation. Biol Pharm Bull 2005; 28:1385-8. [PMID: 16079479 DOI: 10.1248/bpb.28.1385] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Nedaplatin is known to exhibit antitumor activity similar to that of cisplatin. However, concerning side effects, nedaplatin causes renal toxicity less frequently than cisplatin. In this study, we compared the incidence of renal toxicity between cisplatin and nedaplatin by investigating the difference in kidney tissue accumulation. Kidney tissue accumulation of cisplatin administered at 3.75 mg/kg was similar to that of nedaplatin administered at 24 mg/kg. At these doses, the plasma creatinine level and urinary excretion of glucose and N-acetyl-beta-D-glucosaminidase (NAG) similarly increased. There was a correlation between kidney accumulation of cisplatin and nedaplatin and the increases in plasma creatinine level and urinary excretion of NAG. Therefore, our results suggest that nedaplatin less frequently causes renal toxicity in comparison to cisplatin due to lower kidney accumulation.
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Affiliation(s)
- Yoshiko Kawai
- Division of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
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Kohda Y, Kawai Y, Iwamoto N, Matsunaga Y, Aiga H, Awaya A, Gemba M. Serum thymic factor, FTS, attenuates cisplatin nephrotoxicity by suppressing cisplatin-induced ERK activation. Biochem Pharmacol 2005; 70:1408-16. [PMID: 16154539 DOI: 10.1016/j.bcp.2005.08.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2005] [Revised: 08/07/2005] [Accepted: 08/08/2005] [Indexed: 01/09/2023]
Abstract
Serum thymic factor (FTS), a thymic peptide hormone, has been reported to attenuate the bleomycin-induced pulmonary injury and also experimental pancreatitis and diabetes. In the present study, we investigated the effect of FTS on cis-diamminedichloroplatinum II (cisplatin)-induced nephrotoxicity. We have already demonstrated that cephaloridine, a nephrotoxic antibiotic, leads to extracellular signal-regulated protein kinase (ERK) activation in the rat kidney, which probably contributes to cephaloridine-induced renal dysfunction. The aim of this study was to examine the effect of cisplatin on ERK activation in the rat kidney and also the effect of FTS on cisplatin-induced nephrotoxicity in rats. In vitro treatment of LLC-PK1 cells with FTS significantly ameliorated cisplatin-induced cell injury. Treatment of rats with intravenous cisplatin for 3 days markedly induced renal dysfunction and increased platinum contents in the kidney cortex. An increase in pERK was detected in the nuclear fraction prepared from the rat kidney cortex from days 1 to 3 after injection of cisplatin. FTS suppressed cisplatin-induced renal dysfunction and ERK activation in the kidney. FTS did not influence any Pt contents in the kidney after cisplatin administration. FTS has been shown to enhance the in vivo expression of heat shock protein (HSP) 70 in the kidney cortex. The beneficial role of FTS against cisplatin nephrotoxicity may be mediated in part by HSP70, as suggested by its up-regulation in the kidney cortex treated with FTS alone. Our results suggest that FTS participates in protection from cisplatin-induced nephrotoxicity by suppressing ERK activation caused by cisplatin.
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Affiliation(s)
- Yuka Kohda
- Division of Pharmacology, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Osaka 569-1094, Japan.
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Smith JA, Ngo H, Martin MC, Wolf JK. An evaluation of cytotoxicity of the taxane and platinum agents combination treatment in a panel of human ovarian carcinoma cell lines. Gynecol Oncol 2005; 98:141-5. [PMID: 15963813 DOI: 10.1016/j.ygyno.2005.02.006] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2004] [Revised: 02/01/2005] [Accepted: 02/04/2005] [Indexed: 11/25/2022]
Abstract
OBJECTIVES The objectives of this study were to determine the optimum schedule for combination of taxane and platinum agents in human ovarian carcinoma cell lines. METHODS Cell growth inhibition was determined by the standard MTT assay and an IC(50) was calculated for docetaxel, paclitaxel, cisplatin, and carboplatin in seven human ovarian cancer cell lines (CAOV-3, OVCAR-3, SKOV-3, ES-2, OV-90, TOV-112D, and TOV-21G). The IC(50) was defined as the drug concentration required for a 50% reduction in optical density. Cytotoxicity assays were performed with four sequential combinations of a taxane and a platinum compound. In each combination, cell lines were treated with the appropriate IC(50) of the drugs for varying time increments between 3 and 24 h. Controls were no drug, each agent alone and the combination of both. Results were obtained via manual cell counting with a hemocytometer. RESULTS The inhibitory concentration to achieve 50% cell death (IC(50)) was determined for each compound in each cell line. The IC(50) ranged from 0.8 to 1.7 nM, 0.7 to 1.8 nM for docetaxel and paclitaxel, respectively, and 17.4 to 25.7 microM, 15.1 to 25.7 microM for cisplatin and carboplatin, respectively. CONCLUSION In this study the combination of docetaxel plus cisplatin was considerably more active in vitro than any of the other taxane plus platinum agent combinations evaluated in the panel of human ovarian cancer cell lines. In vitro activity was similar to previously report clinical studies comparing taxane and platinum combination regimens. This suggests the combination of docetaxel with cisplatin will have enhanced clinical activity compared to the paclitaxel plus carboplatin regimen.
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Affiliation(s)
- Judith A Smith
- Department of Gynecologic Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1439, USA.
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Tanaka R, Takii Y, Shibata Y, Ariyama H, Qin B, Baba E, Kusaba H, Mitsugi K, Harada M, Nakano S. In vitro sequence-dependent interaction between nedaplatin and paclitaxel in human cancer cell lines. Cancer Chemother Pharmacol 2005; 56:279-85. [PMID: 15875187 DOI: 10.1007/s00280-004-0991-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2004] [Accepted: 11/19/2004] [Indexed: 12/15/2022]
Abstract
PURPOSE To define the most effective combination schedule of paclitaxel and nedaplatin, a new platinum derivative, we investigated the in vitro interaction between these drugs in AZ-521 and NUGC-4 gastric adenocarcinoma and KSE-1 esophageal squamous carcinoma cell lines. MATERIALS AND METHODS Cytotoxic activity was determined by the WST-1 assay. Different treatment schedules of the two drugs were compared and evaluated for synergism, additivity, or antagonism using a quantitative method based on the median-effect principle of Chou and Talalay. Cell-cycle perturbation and apoptosis were evaluated by means of flow cytometry. RESULTS Upon 24-h sequential exposure, the sequence paclitaxel followed by nedaplatin induced greater than additive effects in all of the cell lines, with synergistic interactions in NUGC-4 and KSE-1 cells. By contrast, antagonistic effects were observed with the reverse sequence. Simultaneous treatment resulted in either a synergistic or antagonistic effect, depending on the cell line. Therefore, the sequence paclitaxel followed by nedaplatin appears most active, at least in these three cell lines. Flow cytometric analyses at IC50 indicated that paclitaxel induced G2/M arrest with subsequent induction of apoptosis (56%) in the sub-G1 phase. When paclitaxel preceded nedaplatin, apoptosis was most prominent (70%) with pronounced G2/M arrest. By contrast, the reverse sequence yielded only 28% induction of apoptotic cells, with almost identical cell-cycle distribution patterns to those observed with nedaplatin alone, indicating that the activity of paclitaxel is abolished by pretreatment with nedaplatin. CONCLUSIONS Our findings suggest that the interaction of nedaplatin and paclitaxel is highly schedule dependent and that the sequential administration of paclitaxel followed by nedaplatin should be thus incorporated into the design of a clinical trial.
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Affiliation(s)
- Risa Tanaka
- First Department of Internal Medicine and Department of Biosystemic Science of Medicine, Graduate School of Medicine, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan
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Yoshiyama Y, Yamaguchi K, Matsuo K, Kurokawa M, Kanke M. The effect of fosfomycin on nedaplatin-induced nephrotoxicity in rats. J Infect Chemother 2005; 11:14-7. [PMID: 15729482 DOI: 10.1007/s10156-004-0361-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2004] [Accepted: 11/11/2004] [Indexed: 10/25/2022]
Abstract
The effect of coadministration of fosfomycin (FOM) on nedaplatin-induced nephrotoxicity in rats was investigated for 6 days. FOM decreased nedaplatin-induced nephrotoxicity, as shown by reduced blood urea nitrogen (BUN), serum creatinine levels, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG). Further, there were fewer histopathological signs of nephrotoxicity in the groups treated with the combination of nedaplatin and FOM as compared with the nedaplatin-alone group. The concentration of nedaplatin was significantly lower in the renal cortex of rats treated with the combination of nedaplatin and FOM as compared with those treated with nedaplatin alone (p < 0.05). In conclusion, the concomitant administration of FOM and nedaplatin may help to achieve a chemotherapeutic strategy that reduces the nephrotoxic effects of nedaplatin.
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Affiliation(s)
- Yuji Yoshiyama
- Division of Clinical Pharmacy, Kyoritsu University of Pharmacy, 1-15-30 Shibakoen, Minato-ku, 105-8512, Tokyo, Japan.
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Teh B, Kobayashi W, Narita K, Fukui R, Kimura H. Superselective docetaxel–nedaplatin combined infusion concurrent with radiation therapy in advanced oral cancers. ACTA ACUST UNITED AC 2004. [DOI: 10.1016/j.ooe.2004.08.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Kurita H, Yamamoto E, Nozaki S, Wada S, Furuta I, Kurashina K. Multicenter phase I trial of induction chemotherapy with docetaxel and nedaplatin for oral squamous cell carcinoma. Oral Oncol 2004; 40:1000-6. [PMID: 15509491 DOI: 10.1016/j.oraloncology.2004.05.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2004] [Accepted: 05/06/2004] [Indexed: 11/15/2022]
Abstract
A phase I study of combination neoadjuvant chemotherapy with docetaxel (DOC) and nadaplatin (CDGP) was conducted in patients with untreated, advanced but operable oral squamous cell carcinoma. DOC was administered (one-hour i.v. infusion) on day 1 followed by CDGP (one-hour i.v. infusion). The dose levels of DOC and CDGP tested were 60/70, 60/80, 60/90, 60/100, and 70/100 (mg/m(2)). Fifteen patients enrolled in this study and median age was 60 years. Dose-limiting toxicity (DLT) occurred in one of six patients at DOC dose of 60 mg/m(2) and CDGP dose of 100 mg/m(2). The DLT was diarrhea. Because one additional patient at this dose-level developed grade 4 neutropenia lasting for 4 days that approached DLT and because fear of severe hematological problems was predicted, further dose escalation was not performed. This combination chemotherapy is active and well tolerated and warrants a phase II study. We recommended 60 mg/m(2) DOC and 100 mg/m(2) CDGP for phase II study.
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Affiliation(s)
- Hiroshi Kurita
- Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Japan
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Ita M, Okafuji M, Fukuda K, Mitsuoka K, Hanakita T, Hayatsu Y. Concurrent chemoradiotherapy with new platinum compound nedaplatin in oral cancer. Oral Oncol 2003; 39:144-9. [PMID: 12509967 DOI: 10.1016/s1368-8375(02)00035-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Eleven patients with oral cancer were treated with the new platinum agent, nedaplatin, and 5-fluorouracil and simultaneous radiation therapy. The regimen was of 5 days' duration: 5-fluorouracil 400-500 mg/m(2) (days 1-5), nedaplatin 80-90 mg/m(2) (day 4), and a total radiation dose of 8-10 Gy (days 1-5). Of the 11 patients, 4 (36.4%) showed complete response and 5 (45.4%) showed partial response; the total response rate was 81.8%. Major side effects were hypochromia (27%), leukopenia (64%), granulocytopenia (55%), thrombocytopenia (36%), nausea and vomiting (82%), and mucositis (45%). Toxicity was grade 2 or less in most of the 11 patients. The results indicate that the regimen composed of combination chemotherapy with nedaplatin and radiation therapy is effective in the treatment of patients with squamous cell carcinoma of the oral region.
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Affiliation(s)
- Masamichi Ita
- Department of Oral and Maxillofacial Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
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Fuwa N, Kodaira T, Kamata M, Matsumoto A, Furutani K, Tachibana H, Ito Y. Phase I study of combination chemotherapy with 5-fluorouracil (5-FU) and nedaplatin (NDP): adverse effects and eecommended dose of NDP administered after 5-FU. Am J Clin Oncol 2002; 25:565-9. [PMID: 12477999 DOI: 10.1097/00000421-200212000-00006] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
When nedaplatin (NDP) was used as a single agent in the phase I study, the dose-limiting toxicity (DLT) was thrombocytopenia and the recommended dose (RD) was 100 mg/m2. However, the DLT, maximum tolerated dose (MTD) and RD of NDP used in combination with 5-fluorouracil remained unknown. Therefore, we performed this study to assess the DLT and RD of NDP administered after 5-fluorouracil (5-FU). In this study, 5-FU was administered to 38 patients at a fixed dose (700 mg/m2/d on days 1-5) and NDP administered on day 6 at an initial dose of 80 mg/m2, which was subsequently increased to 100, 120, 130, 140, 150, and 160 mg/m2. The DLT of NDP was leukopenia and its MTD and RD were 160 and 150 mg/m2, respectively. Concerning impairment of renal function, only two patients had a grade I increase in serum creatinine. There were 19 responders (50%, 19/38) achieving partial response or complete response in the evaluation of antitumor effect. The result of this study is notable in that administration of 5-FU before NDP allows the dose of NDP to be substantially increased.
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Affiliation(s)
- Nobukazu Fuwa
- Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
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Vermorken JB. The integration of paclitaxel and new platinum compounds in the treatment of advanced ovarian cancer. Int J Gynecol Cancer 2001; 11 Suppl 1:21-30. [PMID: 11488999 DOI: 10.1046/j.1525-1438.2001.11(suppl.1)sup1021.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
There has been a steady improvement in the survival of patients with advanced ovarian cancer. This has been the result of a more skilled surgical approach to these patients and the development of more effective chemotherapy with a better integration of both modalities in first-line treatment. The current optimal chemotherapeutic approach consists of a platinum compound together with paclitaxel. This recommendation is based upon level I evidence of two large randomized trials which established that the combination of paclitaxel-cisplatin was superior to cyclophosphamide-cisplatin. The long-term follow-up of one of these studies continues to show a significant difference in survival at 5 years. Neurotoxicity has been problematic with these regimens, in particular when paclitaxel was given with the higher dosed shorter infusion schedule, as was done in the European-Canadian Intergroup study. Several approaches to reduce this toxicity have been studied. Among these are the use of different paclitaxel infusion schedules, and the application of less neurotoxic platinum compounds. Weekly paclitaxel has a different toxicity profile than the higher dosed three-weekly schedules, with less neutropenia, alopecia, arthralgia and neurotoxicity. Four platinum compounds are currently marketed: cisplatin, carboplatin, oxaliplatin, and nedaplatin. Of these only cisplatin, carboplatin, and nedaplatin have been approved for the treatment of patients with ovarian cancer (nedaplatin only in Japan). The equivalence of carboplatin and cisplatin has been suggested from trials without a taxoid. Three randomized studies of paclitaxel-carboplatin vs. paclitaxel-cisplatin concluded that paclitaxel-carboplatin is the preferred regimen in terms of (less) toxicity and, where studied, in terms of quality of life. So far, no difference in response rates or progression-free survival has been shown. More mature data on overall survival are awaited. Oxaliplatin (a diaminocyclohexane platinum compound) is of interest because it is only partially cross-resistant with cis- or carboplatin and devoid of severe bone marrow suppression, nephrotoxicity, or ototoxicity. Its dose-limiting toxicity is an unusual form of sensory neuropathy, which is cumulative and, contrary to cisplatin's neurotoxicity, generally reversible. Combinations with other active standard agents, as well as platinum compounds and/or taxoids, are feasible and have shown interesting activity. Similar to carboplatin and oxaliplatin, nedaplatin (cis-diammineglycolatoplatinum) can be given without hydration; its dose-limiting toxicity is myelosuppression, in particular thrombocytopenia. Although activity has been shown, no data from randomized comparative trials are available to allow a judgement on its potential advantages.
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Affiliation(s)
- J B Vermorken
- Department of Medical Oncology, University Hospital Antwerp, Edegem, Belgium.
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Piccart MJ, Lamb H, Vermorken JB. Current and future potential roles of the platinum drugs in the treatment of ovarian cancer. Ann Oncol 2001; 12:1195-203. [PMID: 11697824 DOI: 10.1023/a:1012259625746] [Citation(s) in RCA: 92] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
The discovery of cisplatin more than two decades ago was the most important therapeutic advance in the treatment of ovarian cancer. Today, cisplatin or carboplatin in combination with paclitaxel is the most commonly used first-line treatment for patients with advanced ovarian cancer. Although platinum drugs remain a critical component of chemotherapy in this type of cancer, cumulative toxicities can limit their use. These toxicities include nephrotoxicity, neurotoxicity and ototoxicity with cisplatin and myelosuppression with carboplatin. Although these adverse events can often be managed, the interventions themselves can complicate and add to the costs of treatment. Importantly, acquired resistance to traditional platinum drugs often develops in patients with ovarian cancer and can limit the usefulness of these drugs. Research into new platinum drugs has focused on identifying compounds with improved tolerability profiles and, importantly, those which can circumvent mechanisms of platinum resistance. New platinum drugs currently under development that are showing promise in ovarian cancer include oxaliplatin, nedaplatin, satraplatin, BBR3464 and ZD0473. If the encouraging in vitro activity shown by new compounds, such as ZD0473 and BBR3464, translates into efficacy in the clinic, they may offer an extended spectrum of activity which includes patients with ovarian cancer resistant to the classical platinum drugs.
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Affiliation(s)
- M J Piccart
- Jules Bordet Institute, Chemotherapy Unit, Brussels, Belgium.
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Monk BJ, Alberts DS, Burger RA, Fanta PT, Hallum AV, Hatch KD, Salmon SE. In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human cervical cancers. Gynecol Oncol 1998; 71:308-12. [PMID: 9826477 DOI: 10.1006/gyno.1998.5140] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of cisplatin and carboplatin against fresh cervical cancers from untreated patients. METHODS Specimens were obtained prior to irradiation or radical surgery from 20 patients with locally invasive cervical carcinoma. Cytotoxicity was measured after single cell suspensions were grown in agar using colony counts and incorporation of [3H]thymidine. Nedaplatin and cisplatin were tested at 1 and 10 micrograms/ml dose levels while carboplatin was tested at 10 and 100 micrograms/ml dose levels continuously. When single hour exposures were used, drug doses were increased by 10-fold. RESULTS The median drug concentrations associated with a 50% inhibition of growth (IC50) for nedaplatin, cisplatin, and carboplatin were 0.435, 0.73, and 18.6 micrograms/ml, respectively. At 10 micrograms/ml for both cisplatin and nedaplatin and 100 micrograms/ml for carboplatin, cisplatin was the most active drug with 70% of tumors sensitive (</=50% survival relative to control plates) to cisplatin and 45 and 50% sensitive to nedaplatin and carboplatin, respectively (P = 0.015, P = 0.074). Six of 20 (30%) tumors resistant to cisplatin were also resistant to nedaplatin and carboplatin. CONCLUSION At doses approximating clinically achievable drug concentrations as defined by the mean plasma concentration time product, cisplatin appears more cytotoxic in vitro than either carboplatin or nedaplatin among chemotherapy-naive cervical cancers. However, nedaplatin and carboplatin are also active agents with similar activity. Since differences in drug sensitivity may be related to subtle differences in dose and schedule and the pharmacokinetics and safety profile of nedaplatin are favorable, clinical trials of nedaplatin are indicated.
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Affiliation(s)
- B J Monk
- Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Lubbock, Texas, 79430, USA
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Itoh K, Yamashita T, Wakita H, Watanabe Y, Kodama K, Fujii H, Minami H, Ohtsu T, Igarashi T, Sasaki Y. Successful treatment with nedaplatin in patients with ovarian cancer that recurred after platinum-containing chemotherapy: report of two cases. Jpn J Clin Oncol 1998; 28:343-6. [PMID: 9703864 DOI: 10.1093/jjco/28.5.343] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
We report the successful treatment with nedaplatin of two cases of ovarian cancer that recurred after platinum-containing chemotherapy. A 52-year-old woman presented in June 1994 with massive accumulation of ascitic fluid. Pathological diagnosis of the specimen obtained at surgery in July 1994 was serous papillary adenocarcinoma of the ovary. In September 1995, approximately seven months after the completion of six cycles of CAP chemotherapy (cyclophosphamide, adriamycin and cisplatinum), she was referred to our hospital because of massive accumulation of ascitic fluid. The carbohydrate antigen 125 (CA-125) value was 485 U/ml. Cytologic study of her ascitic fluid was positive for adenocarcinoma cells. She did not respond to intravenous irinotecan and two cycles of intraperitoneal cisplatin. Nedaplatin 100 mg/m2 was administered. Complete response was achieved in September 1996 and continued for four months with a total of seven cycles of nedaplatin. The second case was a 60-year-old woman who was admitted to our hospital in December 1994 because of ascitic fluid. Diagnosis of ovarian cancer was based on an elevated level of CA-125 (1380 U/ml). Treatment with CAP and CC (cyclophosphamide and carboplatin) maintained a partial response for seven months. In August 1996, her disease progressed, although she was receiving CC therapy. Nedaplatin 100 mg/m2 was administered. Partial response was achieved again in November 1996 and continued for four months, with a total of five cycles of nedaplatin. In the light of our experience, treatment with nedaplatin in a patient with recurrent ovarian cancer might be worthwhile as palliative chemotherapy.
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Affiliation(s)
- K Itoh
- Division of Oncology and Hematology, National Cancer Center Hospital East, Chiba, Japan
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