The platelet-sparing effect of paclitaxel is not related to changes in the pharmacokinetics of carboplatin

Abstract

Purpose: To determine whether the platelet-sparing effect of paclitaxel is related to changes in pharmacology of carboplatin. Methods: A group of 32 patients with epithelial ovarian cancer were treated with intraperitoneal (i.p.) carboplatin-based chemotherapy with carboplatin alone or in combination with cyclophosphamide or paclitaxel, and the relationship between the pharmacology of serum platinum and thrombocytopenia was examined. The target AUC of i.p. carboplatin was 6.5 mg·min/ml. Cyclophosphamide was administered intravenously at 400 mg/m² after i.p. carboplatin and paclitaxel at 175 mg/m² was given before i.p. carboplatin. Results: Ten patients received i.p. carboplatin alone, 10 received cyclophosphamide and 12 received paclitaxel. The ages of the patients, body surface area, serum creatinine, platelet count before chemotherapy, and the total dose of carboplatin in each patient were similar in all groups. The measured AUC, C_max, T_1/2, and MRT were similar in these groups. The nadir platelet counts were significantly higher (P=0.0018) in patients treated with i.p. carboplatin with paclitaxel (12.1±4.3×10⁴/mm³) compared with carboplatin alone (5.2±3.3×10⁴/mm³) or with cyclophosphamide (5.2±4.8×10⁴/mm³). The percentage decrease in platelet counts was significantly lower (62.5±18.2%) in patients treated with paclitaxel than in the other two groups (81.5±12.6% carboplatin alone, 88.7±7.9% with cyclophosphamide). Conclusion: The addition of paclitaxel or cyclophosphamide to i.p. carboplatin did not alter the pharmacology of serum platinum. Thrombocytopenia was significantly less in patients treated with carboplatin in combination with paclitaxel. The platelet-sparing effect of paclitaxel is not related to changes in the pharmacology of carboplatin.