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Erlotinib and vinorelbine in advanced malignant solid tumors: a phase I study
Angela M Davies1, Cheryl Ho, Paul J Hesketh
1Davis Cancer Center, University of California, 4501 X Street, Suite 3016, Sacramento, CA 95817, USA. angela.davies@ucdmc.ucdavis.edu
Investigational New Drugs
|April 19, 2007
Summary
This phase I trial found the maximum tolerated dose of erlotinib and vinorelbine combination therapy for advanced non-small cell lung cancer (NSCLC) was 25 mg/m2 vinorelbine with 100 mg erlotinib, but it showed significant toxicity.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Erlotinib is an oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI).
- Vinorelbine is a vinca alkaloid that inhibits mitosis.
- Both agents are used in advanced non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To establish the feasibility and safety of combining erlotinib and vinorelbine.
- To determine the maximum tolerated dose (MTD) of this combination therapy.
- To evaluate the combination's efficacy in patients with advanced solid tumors.
Main Methods:
- A phase I study involving patients with advanced solid tumors.
- Treatment involved intravenous vinorelbine on days 1 and 8, and daily oral erlotinib on a 21-day schedule.
- Dose escalation levels for vinorelbine/erlotinib were 25 mg/m²/100 mg, 25/150 mg, and 30/150 mg.
Main Results:
- Sixteen patients were enrolled, mostly with NSCLC.
- Dose-limiting toxicities included febrile neutropenia (25%) and grade 5 infection.
- No objective radiologic responses were observed; eight patients had stable disease.
Conclusions:
- The MTD was determined to be vinorelbine 25 mg/m² (days 1, 8) with erlotinib 100 mg/day.
- The combination demonstrated a high rate of febrile neutropenia.
- Further exploration of this combination was halted due to later findings on erlotinib's efficacy in NSCLC.
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