The CancerWeb Report, What's New In Cancer: November, 1996
Lung Cancer

• Tobacco carcinogen acts at p53 sites that are mutated in lung cancer - The carcinogen benzo[a]pyrene occurs at levels of 20-40 nanograms per cigarette. It is metabolized in the body to the active carcinogen, a compound known as BPDE. Researchers at the Beckman Research Institute in Duarte, California, and the M.D. Anderson Cancer Center in Houston, Texas, treated human cells, including bronchial epithelial cells, with BPDE, and looked at the effects on the p53 gene. Mutations of the p53 tumor suppressor gene are among the most common genetic changes seen in human cancers. In experiments described in an article in the October 18, 1996 issue of Science, they found that the active carcinogen combined with the guanine bases at specific positions along the DNA chain of the p53 gene, namely at what are termed codons 157, 248, and 273. These are the same positions in the gene, also referred to as major hot spots, at which mutations are found in lung cancers. (Denissenko, Science 274:430, 1996)

  Editor's Comment: - This finding probably represents the first example of a direct link between a cigarette smoke carcinogen and specific mutations in human cancer. Codons 248 and 273 are commonly affected in other cancers also. Smoking is associated with increased incidence of several cancers, although the link is weaker than it is for lung cancer. The study should be extended to a range of both tobacco-related and non-related cancers.

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• Vinorelbine superior to vindesine in treatment of lung cancer - Current chemotherapy regimens may give response rate of around 30% in non-small-cell lung cancer, but it is questionable whether they provide a clinically significant improvement in survival. The vinca alkaloid vindesine is among the drugs currently used, often in combination with cisplatin. A new semisynthetic vinca alkaloid, vinorelbine, has produced some responses when used alone in early trials, and an article in the October, 1996 issue of Annals of Oncology by doctors in the Japanese Lung Cancer Cooperative Study Group presents one such study. They compared vindesine and vinorelbine alone and in combination with cisplatin in 204 patients with untreated Stage III and IV non-small-cell lung cancer. In the first stage of the study patients were treated with 4 cycles of vinorelbine alone or vindesine alone, and those who responded were continued on the same drugs. Response rates were 31.1% for vinorelbine versus 8.9% for vindesine. Median response duration was longer for vinorelbine at 18.5 weeks versus 11.7 weeks for vindesine, but overall survival, although better for vinorelbine (52.4 weeks compared with 43.6 weeks), was not statistically significantly greater. Among those patients who failed to respond to treatment with single drug, 33 who were switched from vinorelbine to vindesine plus cisplatin failed to respond, whereas of 49 on vindesine who were switched to vinorelbine plus cisplatin, 13 responded. Vinorelbine had similar toxicity to vindesine as regards the bone marrow except for more frequent anemia with vinorelbine, and the latter gave slightly more local skin reaction, but had significantly less effect on the nervous system. (Furuse, Ann Oncol 7:815, 1996)

  Editor's Comment: - Vinorelbine is an important new member of the vinca alkaloid group which is finding a range of uses. For example, an article in the November, 1996 issue of the Journal of Clinical Oncology by Doctors in Argentina (Leone, J Clin Oncol 14:2993, 1996)describes responses in 58% of patients with metastatic breast cancer when vinorelbine was used in conjunction with ifosfamide.