title: Phase I trial of topotecan plus vinorelbine with/without filgrastim (G-CSF) in patients with refractory malignancies.
abstract: 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.
authors.affiliation: Department of Medicine, Indiana University, Indianapolis, Indiana, U.S.A.
authors.forename: Nasser H
authors.initials: NH
authors.lastname: Hanna
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gordon
authors.forename: Karen
authors.initials: K
authors.lastname: Fife
authors.forename: Alan B
authors.initials: AB
authors.lastname: Sandler
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D018365:Neoplasm, Residual / Q000188:drug therapy*; D009503:Neutropenia; D011994:Recombinant Proteins; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D019772:Topotecan; D000069585:Filgrastim; D000077235:Vinorelbine