A phase I trial of MTA and gemcitabine in patients with locally advanced or metastatic cancer.
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 1 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.
Adjei
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Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Erlichman
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C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004791:Enzyme Inhibitors; D005260:Female; D005493:Folic Acid Antagonists; D005706:Gallbladder Neoplasms / Q000188:drug therapy / Q000473:pathology; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D000068437:Pemetrexed; D000093542:Gemcitabine
D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine