Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function
ABSTRACT To characterize the pharmacokinetics and pharmacodynamics of oxaliplatin in cancer patients with impaired renal function.
Thirty-four patients were stratified by 24-h urinary creatinine clearance (CrCL) into four renal dysfunction groups: group A (control, CrCL, >or=60 mL/min), B (mild, CrCL, 40-59 mL/min), C (moderate, CrCL, 20-39 mL/min), and D (severe, CrCL, <20 mL/min). Patients were treated with 60 to 130 mg/m2 oxaliplatin infused over 2 h every 3 weeks. Pharmacokinetic monitoring of platinum in plasma, plasma ultrafiltrates, and urine was done during cycles 1 and 2.
Plasma ultrafiltrate platinum clearance strongly correlated with CrCL (r2 = 0.712). Platinum elimination from plasma was triphasic, and maximal platinum concentrations (Cmax) were consistent across all renal impairment groups. However, only the beta-half-life was significantly prolonged by renal impairment, with values of 14.0 +/- 4.3, 20.3 +/- 17.7, 29.2 +/- 29.6, and 68.1 h in groups A, B, C, and D, respectively (P = 0.002). At a dose level of 130 mg/m2, the area under the concentration time curve increased in with the degree of renal impairment, with values of 16.4 +/- 5.03, 39.7 +/- 11.5, and 44.6 +/- 14.6 mug.h/mL, in groups A, B, and C, respectively. However, there was no increase in pharmacodynamic drug-related toxicities. Estimated CrCL using the Cockcroft-Gault method approximated the measured 24-h urinary CrCL (mean prediction error, -5.0 mL/min).
Oxaliplatin pharmacokinetics are altered in patients with renal impairment, but a corresponding increase in oxaliplatin-related toxicities is not observed.
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ABSTRACT: The purpose of this study is to assess the feasibility of salvage chemotherapy with gemcitabine and oxaliplatin (GEMOX) for Japanese patients with refractory testicular germ cell cancer. Eleven patients were treated with GEMOX. All had experienced disease progression or recurrence and had been treated with the standard induction chemotherapy and at least one cycle of cisplatin-based salvage chemotherapy (median 6 cycles) before the start of GEMOX. GEMOX consisted of gemcitabine 1,000 mg/m(2) intravenously on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 1. Two patients (18 %) achieved a complete response (CR) after GEMOX and surgical resection of residual tumor. One additional patient responded to GEMOX, but was forced to discontinue treatment due to sensory neuropathy. This patient achieved CR after further treatment with irinotecan-based chemotherapy and surgery. All three patients have remained continuously free from disease progression at a median follow-up duration of 24 months. Sixty-four per cent of patients developed grade 3 leukocytopenia and 82 % developed grade 3 or higher thrombocytopenia but they were all managed with routine supportive care. Sensory neuropathy was frequently seen but no patient experienced neurotoxicity higher than grade 3. GEMOX as salvage chemotherapy is tolerable for intensively pretreated Japanese patients. GEMOX may offer a chance of long-term disease-free status even after failure of multiple cycles of chemotherapy.International Journal of Clinical Oncology 03/2014; 19(6). DOI:10.1007/s10147-014-0667-5 · 2.17 Impact Factor
Hospital pharmacy 09/2010; 45(9):685-693. DOI:10.1310/hpj4509-685
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ABSTRACT: Background Sorafenib is the only systemic treatment that has shown a significant benefit in overall survival (OS) and in progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients. No standard of care currently exists for second-line treatment. The association of Gemcitabine-Oxaliplatine (GEMOX) has shown efficacy in the first-line setting. The aim of this study was to evaluate the efficacy of GEMOX after failure of at least one line of anti-angiogenic (AA) therapy. Patient and methods We performed a multicenter retrospective analysis of advanced HCC patients that received GEMOX chemotherapy after progression on at least one line of AA therapy. Results We analyzed a total of 40 patients that received a median of 7 cycles of GEMOX over a 6-year period. Grade 3/4 toxicity was observed in 25 % of patients, mainly neurotoxicity, thrombocytopenia and neutropenia in 12.5 %, 5 % and 5 % of patients respectively. Grade <3 toxicity was mainly hematological and neurotoxicity. In the sub-cohort of 35 patients evaluable for response, partial response was observed in 20 % of patients, while 46 % had stable disease. Median OS was 8.3 months, with a 6-month OS rate of 59 %. Median PFS was 3.1 months. Prognostic factors for OS in univariable analysis were the performance status and AFP levels at GEMOX start, and the BCLC score at diagnosis. None of these factors were prognostic for PFS or tumor response. Conclusion The GEMOX schedule seems to show clinical activity and an acceptable toxicity profile in advanced HCC patients who progressed after anti-angiogenic treatment. The observed median OS of over 8 months is encouraging in this population of heavily pretreated patients. These results would merit confirmation in a prospective randomized study.Investigational New Drugs 04/2014; 32(5). DOI:10.1007/s10637-014-0100-y · 2.93 Impact Factor