Decreased topotecan platelet toxicity with successive topotecan treatment cycles in advanced ovarian cancer patients

The dose-limiting toxicities of the DNA topoisomerase I inhibitor topotecan are hematological. We prospectively analyzed the platelet toxicity pattern in patients receiving topotecan to optimize the clinical management of topotecan hematotoxicity, Twenty-one advanced ovarian cancer patients, all pretreated with cisplatin and paclitaxel, were treated with 1.25 mg/m(2)/day topotecan as a 30 min infusion for 5 days, every 3 weeks, No prophylactic granulocyte colony stimulating factor (G-CSF) was given, No topotecan dose reduction was planned according to hematologic toxicity. One hundred and thirty-three topotecan courses were administered (median per patient 6; range: 1-15). Despite no dose reduction, the mean platelet nadir values were significantly less pronounced at cycle 2 than at cycle 1 (82 versus 46 x 10(3)/mm(3), p=0.0007), Similar differences were found between cycle 1 and any following cycle, The percent of patients experiencing grade 4 thrombocytopenia decreased from 43% at the first cycle, to 15 and 19% at the second and third courses, respectively (p=0.058). We conclude that the currently recommended topotecan schedule is feasible in heavily pretreated ovarian cancer patients without prophylactic G-CSF, The severity of topotecan-induced thrombocytopenia is maximal at the first cycle but significantly decreases from the second cycle in the absence of dose reduction, [(C) 1999 Lippincott Williams & Wilkins.]