Mutational activation of the K-ras oncogene and the effect of chemotherapy in advanced adenocarcinoma of the lung: a prospective study.

Rodenhuis S, Boerrigter L, Top B, Slebos RJ, Mooi WJ, van't Veer L, van Zandwijk N
J Clin Oncol. 1997 15 (1): 285-91

PMID: 8996154 · DOI:10.1200/JCO.1997.15.1.285

PURPOSE - To determine whether the clinical course and the response to chemotherapy of patients with advanced adenocarcinoma of the lung depends on the presence or absence of a ras mutation in the tumor. Mutational activation of K-ras is a strong adverse prognostic factor in stage I or II lung cancer and laboratory studies have suggested that ras mutations lead to resistance against ionizing radiation and chemotherapy.

PATIENTS AND METHODS - Patients with advanced adenocarcinoma of the lung with measurable or assessable disease received chemotherapy with mesna, ifosfamide, carboplatin, and etoposide (MICE). Archival biopsies, fresh biopsies, or fine-needle aspirations were tested for the presence of ras gene mutations. Associations of ras mutations with clinical characteristics, response to chemotherapy, and survival were studied.

RESULTS - The presence or absence of ras gene mutations could be established in 69 of 83 patients (83%). A total of 261 courses of MICE were administered to 62 informative patients, 16 of whom were shown to have a K-ras mutation-positive tumor. The frequency of mutations (26%) and the type of mutations closely matched the pattern we have previously reported in operable disease. Patients with a ras mutation in their tumor were more likely to have a close relative with lung cancer, but other clinical characteristics, such as pattern of metastases, response, and survival, were similar between the ras mutation-positive and ras mutation-negative groups.

CONCLUSION - Patients with advanced lung adenocarcinoma who harbor a ras mutation may have major responses to chemotherapy and have similar progression-free and overall survival as patients with ras mutation-negative tumors. K-ras mutations may represent one of several ways in which early tumors are enabled to metastasize to distant sites.

MeSH Terms (17)

Adenocarcinoma Adult Aged Carboplatin Carcinoma, Non-Small-Cell Lung Etoposide Female Gene Expression Regulation, Neoplastic Genes, ras Humans Ifosfamide Lung Neoplasms Male Middle Aged Mutation Prospective Studies Survival Analysis

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