Phase I study of vinorelbine and ifosfamide in advanced non-small-cell lung cancer
| Autor: | Rosemarie Mick, Brian L. Samuels, Harvey M. Golomb, L. C. Drinkard, Alfred Guaspari, Gregory A. Masters, Ai-ly Hsieh, Philip C. Hoffman, Everett E. Vokes |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Lung Neoplasms medicine.medical_treatment Neutropenia Vinblastine Vinorelbine Gastroenterology Drug Administration Schedule chemistry.chemical_compound Carcinoma Non-Small-Cell Lung Internal medicine Antineoplastic Combined Chemotherapy Protocols Granulocyte Colony-Stimulating Factor medicine Humans Ifosfamide Lung cancer Aged Neoplasm Staging Chemotherapy Performance status business.industry Middle Aged medicine.disease Survival Analysis Nitrogen mustard Surgery Granulocyte colony-stimulating factor Oncology chemistry Feasibility Studies Female business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 15:884-892 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | PURPOSE We designed a phase I dose-escalation study of vinorelbine on a novel (daily-times-three) schedule with ifosfamide with granulocyte colony-stimulating factor (G-CSF) support to define the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of vinorelbine in this combination. PATIENTS AND METHODS Cohorts of patients with stage IIIB or IV non-small-cell lung cancer (NSCLC) and no prior chemotherapy received vinorelbine starting at 15 mg/m2 on days 1, 2, and 3, and ifosfamide starting at 2.0 g/m2 on days 1, 2, and 3 with G-CSF support for all patients. Cycles were repeated every 21 days. Plasma vinorelbine concentrations were also analyzed. RESULTS Forty-two patients were treated. The median age was 58 years (range, 34 to 75) and 41 had a performance status of 0 or 1. The DLT was neutropenia and sepsis at a maximum-administered vinorelbine dose of 35 mg/m2 for 3 days. The recommended phase II dose was vinorelbine 30 mg/m2 with ifosfamide 1.6 g/m2 both given on 3 consecutive days. The overall response rate was 40% (17 of 42; all partial responders). The median survival duration was 50 weeks, with a 1-year survival rate of 48%. Pharmacokinetic analysis showed that vinorelbine in this combination and on this schedule is cleared 1.5 to two times faster than in single-agent once-weekly studies. CONCLUSION Myelosuppression is the DLT of this regimen with no major subjective toxicities. With tolerable toxicity and an encouraging 1-year survival rate of 48%, further investigation of this new vinorelbine schedule is warranted in this and other combination regimens. |
| Databáze: | OpenAIRE |
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