A Phase I trial of a modified, dose intensive FAMTX regimen (high dose 5-fluorouracil + doxorubicin + high dose methotrexate + leucovorin) with oral uridine rescue Journal Article
| Authors: | Schwartz, G. K.; Christman, K.; Saltz, L.; Casper, E.; Quan, V.; Bertino, J.; Martin, D. S.; Colofiore, J.; Kelsen, D. |
| Article Title: | A Phase I trial of a modified, dose intensive FAMTX regimen (high dose 5-fluorouracil + doxorubicin + high dose methotrexate + leucovorin) with oral uridine rescue |
| Abstract: | BACKGROUND. Dose intensification of 5-fluorouracil (5-FU) is complicated by increased toxicity, 5-FU is a fluorine-substitute analog of uracil. In preclinical studies, administration of oral uridine (Ur) has been shown to allow for dose intensification of 5-Fu with enhancement of its antitumor activity. Therefore, a Phase I trial was designed aimed at dose intensification of 5-FU as a component of a modified 5-FU-doxorubicin- methotrexate (FAMTX) regimen using oral Ur rescue. METHODS. Methotrexate (MTX) was administered to all patients at a fixed dose of 1.5 g/m2. MTX was followed 24 hours later by escalating doses of 5-FU starting at 800 mg/m2 with leucovorin rescue. Cycles of 5-FU and MTX were repeated every 15 days. Every other cycle, patients received doxorubicin ('Adria cycles') at a dose of 30 mg/m2. Oral Ur was administered at a dose of 8 mg/m2 every 6 hours for 12 doses. In the first phase of the study, patients received Ur only if they developed Grade 3 or 4 hematologic toxicity. In the second phase, all patients received Ur 24 hours after 5-FU on all cycles. RESULTS. Without Ur rescue, the maximum tolerated dose (MTD) of 5-FU was 900 mg/m2 on the Adria cycles and 1.1 mg/m2 on the non-adria cycles. With Ur, the MTD of 5-FU increased to 1.2 mg/m2 on the adria cycles and to 1.6 mg/m2 on the non- adria cycles. CONCLUSIONS. In this modified FAMTX regimen, oral Ur administration allowed for dose-intensification of 5-FU, with a 33% increase in the MTD of 5-FU on the Adria cycles and a 45% increase in the MTD of 5-FU dose on the non-Adria cycles. |
| Keywords: | adult; cancer survival; controlled study; aged; middle aged; major clinical study; clinical trial; neutropenia; doxorubicin; fluorouracil; dose response; drug efficacy; methotrexate; neoplasms; controlled clinical trial; leukopenia; antineoplastic combined chemotherapy protocols; antineoplastic activity; folinic acid; patient compliance; phase 1 clinical trial; cancer control; administration, oral; leucovorin; stomach carcinoma; drug tolerance; uridine; oral drug administration; gastric carcinoma; antidotes; uridine derivative; dose intensification; humans; human; male; female; priority journal; article; famtx; oral uridine |
| Journal Title: | Cancer |
| Volume: | 78 |
| Issue: | 9 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 1996-11-01 |
| Start Page: | 1988 |
| End Page: | 1995 |
| Language: | English |
| DOI: | 10.1002/(sici)1097-0142(19961101)78:9<1988::aid-cncr21>3.0.co;2-t |
| PUBMED: | 8909321 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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