Erlotinib and vinorelbine in advanced malignant solid tumors: A phase I study

Angela M. Davies, Cheryl Ho, Paul J. Hesketh, Laurel A Beckett, Primo N Lara, Derick H Lau, David R Gandara

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Erlotinib is an oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). Vinorelbine, a vinca alkaloid, interferes with microtubule assembly inhibiting mitosis during metaphase. Both drugs are commonly used as single agents in the treatment of advanced non small cell lung cancer (NSCLC). Given their efficacy in NSCLC and their non-overlapping toxicity profile, we conducted a phase I study of erlotinib and vinorelbine to establish the feasibility and safety of the combination and to determine the maximum tolerated dose (MTD). Patients and methods: Patients with advanced solid tumors were treated with vinorelbine intravenously on day 1 and 8 and erlotinib orally daily on a 21 day schedule. The dose levels of vinorelbine/erlotinib were 25 mg/m2/100 mg, 25/150 and 30/150. Results: Sixteen patients were enrolled. Five patients were chemo-naïve; 11 had one prior therapy. The majority of patients had NSCLC (n=7). Dose limiting toxicities included febrile neutropenia (4 patients) and grade 5 infection (1 patient). Non-hematologic grade 3/4 toxicities included diarrhea, hypokalemia, infection, dyspnea and mucositis. Of 12 patients assessable for radiologic response, there were no objective responses; eight had stable disease. Conclusions: (1) The MTD was vinorelbine 25 mg/m2 day 1 and 8 with erlotinib 100 mg/day every 21 days. (2) The combination was associated with high rate of febrile neutropenia (25%). (3) Due to subsequent data demonstrating a lack of efficacy of erlotinib in combination with platinum doublets in advanced NSCLC, this combination has not been explored further.

Original languageEnglish (US)
Pages (from-to)351-355
Number of pages5
JournalInvestigational New Drugs
Volume25
Issue number4
DOIs
StatePublished - Aug 2007

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Non-Small Cell Lung Carcinoma
Neoplasms
Febrile Neutropenia
Maximum Tolerated Dose
Vinca Alkaloids
Mucositis
Hypokalemia
vinorelbine
Erlotinib Hydrochloride
Metaphase
Infection
Platinum
Epidermal Growth Factor Receptor
Mitosis
Microtubules
Dyspnea
Protein-Tyrosine Kinases
Diarrhea
Appointments and Schedules
Safety

Keywords

  • EGFR
  • Erlotinib
  • Phase I
  • Vinorelbine

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Erlotinib and vinorelbine in advanced malignant solid tumors : A phase I study. / Davies, Angela M.; Ho, Cheryl; Hesketh, Paul J.; Beckett, Laurel A; Lara, Primo N; Lau, Derick H; Gandara, David R.

In: Investigational New Drugs, Vol. 25, No. 4, 08.2007, p. 351-355.

Research output: Contribution to journalArticle

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