Phase I trial of topotecan plus vinorelbine with/without filgrastim (G-CSF) in patients with refractory malignancies

Nasser H. Hanna, Michael S. Gordon, Karen Fife, Alan B. Sandler

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The purpose of this study was to determine the maximum tolerated dose (MTD) of topotecan plus vinorelbine with and without filgrastim (granulocyte colony-stimulating factor) in refractory solid tumors. Cohorts of three patients with recurrent solid tumors previously treated with no more than one chemotherapy regimen were entered. All patients had a performance status of 0 to 1 with adequate hepatic, renal, and bone marrow function and were treated with topotecan 1.5 mg/m2 intravenously on days 1 to 3 followed by vinorelbine 25 mg/m2 intravenously on days 1 and 8 without filgrastim every 3 weeks. Dose escalation was based on standard criteria for phase I escalation with a maximum of five patients in a cohort until an MTD was defined (first without then with filgrastim). Three patients were treated at dose level 1 (topotecan 1.5 mg/m2 days 1-3 and vinorelbine 25 mg/m2 days 1 and 8) without filgrastim. All three experienced hematologic dose-limiting toxicity (DLT) including grade IV neutropenia in two patients and grade III thrombocytopenia in one patient. An additional two patients, supported with filgrastim, treated at dose level 1 experienced DLT. One patient had dose-limiting neutropenia and the other had significant nonhematologic toxicity. No objective responses were seen, and all patients died within 6 months of entering the trial. The combination of topotecan and vinorelbine was poorly tolerated in the dose and schedule tested in this phase I trial. Subsequent combinations of these drugs, if warranted, should focus on alternate doses, schedules, or routes of administration.

Original languageEnglish (US)
Pages (from-to)337-339
Number of pages3
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Issue number4
StatePublished - Aug 20 2002
Externally publishedYes


  • Filgrastim
  • Topotecan
  • Vinorelbine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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