BIOCHEMICAL MODULATION IN THE TREATMENT OF ADVANCED CANCER - A STUDY OF COMBINED LEUCOVORIN, FLUOROURACIL, AND IODODEOXYURIDINE

Multiple studies have shown that leucovorin-fluorouracil regimens are modestly superior to fluorouracil alone in the treatment of advanced c olorectal cancer. Laboratory data suggest that iododeoxyuridine could further enhance the efficacy of leucovorin-fluorouracil regimens. This report describes the Phase I clinical evaluation of a leucovorin-fluo rouracil-iododeoxyuridine chemotherapy regimen. Twenty-four patients r eceived treatment with leucovorin (500 mg/m(2)), fluorouracil (500 mg/ m(2)), and iododeoxyuridine (escalating doses) on days 1 and 8 of a 21 -day cycle. The maximum tolerated dose of iododeoxyuridine was 1200 mg /m(2), with a recommended Phase II dose of 1000 mg/m(2). Myelosuppress ion (leukopenia) was dose limiting; other commonly observed treatment toxicities were nausea/vomiting, mucositis, and hyperlacrimation. Alth ough the 1200 mg/m(2) dose was tolerated during the initial few cycles of therapy, chronic administration could not be maintained secondary to dose-limiting neutropenia. Since neutropenia was dose limiting, in a follow-up study, 10 patients received a modified regimen (treatment on days 1 and 6 instead of days 1 and 8) with the addition of granuloc yte colony-stimulating factor (days 8-19). The addition of granulocyte colony-stimulating factor, however, did not permit further escalation of the iododeoxyuridine dose. Three partial responses and six minor r esponses were observed. Phase II studies of this regimen are ongoing i n advanced colorectal and advanced pancreatic cancer to determine resp onse rates in these diseases.