Phase I dose escalation study of topotecan combined with alternating schedules of paclitaxel and carboplatin in advanced solid tumors

F. R. Dunphy, T. L. Dunleavy, B. R. Harrison, C. L. Cantrell, J. L. Visconti, S. M. Pincus, J. M. Richart, P. J. Petruska

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Combining topotecan with other cytotoxics has been problematic due to marrow suppression. A phase I trial was initiated to identify the optimal sequence and maximum-tolerated dose of topotecan in combination with paclitaxel and carboplatin. Patients and methods: Patients with advanced cancer and performance status ECOG ≤2. The starting dose was paclitaxel 175 mg/m2 day 1, carboplatin AUC 6.0 day 1, and topotecan 0.5 mg/m2 daily day 1-5 (early sequence). The next course of paclitaxel and carboplatin administration was delayed to day 5 (late sequence). Treatment was repeated every three weeks. After determining maximum-tolerated dose without cytokines, granulocyte colony-stimulating factor (G-CSF) was added and further dose escalation was pursued. Results: Fifty-one patients were entered; men: women ratio 30 : 21. Dose-limiting toxicity (DLT) for the early sequence was neutropenia at doses paclitaxel mg/m2/carboplatin AUC 5/ topotecan mg/m2 (PCT) 175/5/0.75 for four to five days. DLT for the late sequence was neutropenia at PCT doses of 175/5/1.0 for four days. G-CSF 5 μg/kg subcutaneously starting day 6 permitted further topotecan dose escalation. After adding G-CSF, late sequence DLT was neutropenia at doses 175/5/1.25 for four days. Forty-six patients were evaluable for response and of those, there were thirteen partial responses. Conclusions: The late sequence resulted in less toxicity and was better tolerated. The early sequence maximum-tolerated dose (MTD) was 175/6/0.5 for five days. The late sequence MTD was PCT 175/5/0.75 for five days. The late sequence MTD with G-CSF was 175/5/1.0 for four days. The recommended phase II PCT dose is the late sequence 175/5/1.0 for four days with G-CSF.

Original languageEnglish
Pages (from-to)549-555
Number of pages7
JournalAnnals of Oncology
Volume12
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Carboplatin
  • Hycamtin
  • Paclitaxel
  • Phase I
  • Taxol
  • Topotecan

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