Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer – a phase II studyReport as inadecuate




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BMC Cancer

, 2:9

First Online: 02 May 2002Received: 21 November 2001Accepted: 02 May 2002DOI: 10.1186-1471-2407-2-9

Cite this article as: Tomlinson, S.K., Melin, S.A., Higgs, V. et al. BMC Cancer 2002 2: 9. doi:10.1186-1471-2407-2-9

Abstract

Background5-fluorouracil remains the standard therapy for patients with advanced-metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate – leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer.

MethodsNinety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate – 30 mg-m was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV – 500 mg-m. Midway through the leucovorin infusion, patients received 5-fluorouracil – 600 mg-m. This constituted a cycle of therapy and was repeated every 2 weeks until progression.

ResultsThe median age was 64 yrs 34–84 and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting.

ConclusionsThis phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents Irinotecan and-or oxaliplatin are in progress and may prove encouraging.

Abbreviations5-FU5-fluorouracil

PALAN-phosphonacetyl-L-aspartic acid

IFNaα-2aInterferon alfa-2a

PVIProtracted venous infusion

DPDdihydropyrimidine dehydrogenase

MTXMethotrexate

LVLeucovorin

ECOGEastern Cooperative Oncology

F-dUMP5-fluoro-2-deoxyuridine – 5-monophosphate

TSthymidylate synthetase

PRPP5-phosphoribosyl-1-pyrophosphate

FUTP5-fluoriuridine – 5-triphosphate

FNuct5-fluoronucleotide

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-2-9 contains supplementary material, which is available to authorized users.





Author: Shannon K Tomlinson - Susan A Melin - Vetta Higgs - Douglas R White - Paul Savage - Douglas Case - A William Blackstock

Source: https://link.springer.com/







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