Nedaplatin

Nedaplatin is a derivative of cisplatin and DNA damage agent for tumor colony forming units with IC50 of 94 μM.

Multi-institutional prospective study of nedaplatin plus S-1 chemotherapy in recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-containing regimens.[Pubmed:28203299]

Ther Adv Med Oncol. 2017 Feb;9(2):68-74.

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/ m(2), 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 m(2); 50 mg twice daily when 1.25 m(2) BSA < 1.5 m(2); and 60 mg twice daily when BSA 1.5 m(2). 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.

Incidence of and risk factors associated with nedaplatin-related hypersensitivity reactions.[Pubmed:28124284]

Int J Clin Oncol. 2017 Jun;22(3):593-599.

BACKGROUND: Nedaplatin (NDP)-related hypersensitivity reactions (HSRs) trigger adverse clinical events. Prediction and prevention of NDP-HSRs are thus essential to minimize the risk and maximize the benefit of NDP therapy. However, the incidence of NDP-HSRs and the associated risk factors remain unclear. METHODS: We retrospectively examined patients who received NDP monotherapy between April 2011 and July 2015 in Nagoya University Hospital. HSRs severity was defined according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE ver.4). Risk factors for NDP-HSRs were determined using multivariate logistic regression. RESULTS: Of 111 patients who received NDP monotherapy, 90 (81%) were female; median age was 59 years (range, 29-78 years). Eighty-eight patients had gynecological cancer and 20 suffered from head and neck cancer. Eight of 111 patients (7.2%) experienced NDP-HSRs, six of which developed in the second NDP cycle. However, all patients with NDP-HSRs were treated with carboplatin (CBDCA) for more than three cycles. Grade 3 and 4 HSRs developed in 2 patients. NDP-HSRs were significantly associated with a history of CBDCA-HSRs (odds ratio 37.5, 95% confidence interval 5.38-262, p < 0.001) and with the interval between NDP administration and the previous platinum treatment (odds ratio 13.9, 95% confidence interval 1.23-158, p = 0.034). CONCLUSION: The risk of NDP-HSRs increases in patients with a history of CBDCA-HSRs and in those administered NDP for more than 6 months after previous platinum treatment. Such individuals must be closely monitored if given NDP, even if they are expected to benefit from the treatment.

[Analysis of Nedaplatin Dose in Patients with Impaired Renal Function].[Pubmed:28223671]

Gan To Kagaku Ryoho. 2017 Feb;44(2):143-147.

Nedaplatin(NDP)is a platinum derivative anticancer drug.An NDP dose of 100mg/m2 every 4 weeks is recommended in non-elderly Japanese patient because a higher dose may lead to myelosuppression, such as thrombocytopenia.In a pharmacokinetic analysis, thrombocytopenia was significantly correlated with renal function.However, the correct dose in patients with impaired renal function remains unclear.To evaluate the usefulness of dose reduction in patients with renal dysfunction, we conducted a retrospective study.This study included Japanese solid cancer patients who received NDP monotherapy in Nagoya University Hospital between April 2011 and March 2014. Eighty three patients were evaluated and divided into 2 groups based on renal function: a creatinine clearance(Ccr; mL/min)>/=60 group and a Ccr<60 group.The frequency of B Grade 3 thrombocytopenia and neutropenia was significantly higher in the Ccr<60 group than that in the Ccr>/=60 group (3.4% vs 32.0%; p=0.001 and 6.8% vs 32.0%; p=0.005, respectively).In the Ccr<60 group, the frequency of BGrade 3 thrombocytopenia and neutropenia was lower in the reduced dose group than that in standard dose(100mg/m2)group (41.7% vs 23.1%; p=0.410 and 41.7% vs 23.1%; p=0.410, respectively).A multiple logistic regression analysis revealed that NDP dose and serum creatinine were risk factors for the incidence of BGrade 3 thrombocytopenia and neutropenia.These results suggest that NDP dose should be reduced to achieve safe drug treatment in patients with Ccr<60.

Clinical efficacy and safety of gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma.[Pubmed:28230029]

J Cancer Res Ther. 2016 Dec;12(Supplement):C252-C255.

OBJECTIVE: The purpose was to explore the clinical effects and safety of gemcitabine plus Nedaplatin in the treatment of advanced nasopharyngeal carcinoma. MATERIALS AND METHODS: From March 2014 to August 2015, we recruited 63 advanced nasopharyngeal carcinoma patients in our hospital. Moreover, the 62 cases were randomly divided into control group (n = 31) and treatment group (n = 32). Patients in the control groups were treated with 5-fluorouracil 500 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1-5 plus cisplatin 20 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1-5 with 21 days per cycle for 3 cycles; Moreover, patients in the treatment group were given gemcitabine 1000 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1 and 8 plus Nedaplatin 20 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1 with 21 days per cycle for 3 cycles. The objective response rate (ORR) and chemotherapy-associated toxicities were compared between the two groups. RESULTS: After 3 cycle chemotherapy, the ORR was 41.9% and 78.1% in the control and treatment group, respectively, with statistical difference (P < 0.05); The main chemotherapy-related toxicity were hematological toxicity and gastrointestinal reaction with no statistical difference between the two groups (P > 0.05). CONCLUSION: The ORR was relative high for gemcitabine plus Nedaplatin in the treatment of advanced nasopharyngeal carcinoma with main toxicity of hematological toxicity and gastrointestinal reaction.