MTA has demonstrated activity in breast, lung, bladder, and gastrointestinal malignancies in early clinical trials. Gemcitabine is a cytotoxic pyrimidine antimetabolite with broad activity against solid tumors. We have demonstrated sequence-dependent in vitro cytotoxic synergy when gemcitabine exposure preceded MTA exposure in cultured human HCT-8 colon carcinoma cells. A phase I study testing this synergy in patients is in progress. To date, 14 patients with solid tumors have received 42 courses of treatment at a fixed gemcitabine dose of 1,000 mg/m2 on days I and 8 and escalating doses of MTA (200, 300, and 400 mg/m2) given 90 minutes after gemcitabine on day 1. Courses are repeated every 3 weeks. The median number of courses received is three (range, one to seven). National Cancer Institute Common Toxicity Criteria grade 4 hematologic toxicity lasting less than 5 days has been leukopenia and neutropenia. Mild to moderate nonhematologic toxicities include arthralgia, nausea, fatigue, fever, rash, and liver function test abnormalities. One partial response occurred in a patient with previously treated metastatic gallbladder cancer. Dose escalation continues.
|Original language||English (US)|
|Number of pages||5|
|Journal||Seminars in oncology|
|Issue number||2 SUUPL.|
|State||Published - 1999|
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