Randomized phase III Study of 5‐fluorouracil plus high dose folinic acid versus 5‐fluorouracil plus folinic acid plus methyl‐lomustine for patients with advanced colorectal cancer

Dennie V. Jones*, Roger J. Winn, Barry W. Brown, Lawrence B. Levy, Reginald P. Pugh, James L. Wade, Howard M. Gross, Kelly B. Pendergrass, Bernard Levin, James L. Abbruzzese

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background. Metastatic colorectal cancer is generally incurable. The most active regimen available, 5‐fluorouracil (5‐FU) and folinic acid (Leucovorin), produces response rates of approximately 25% to 30%. Methyl‐lomustine is a nitrosourea with modest activity against colorectal cancer. A randomized trial was undertaken to evaluate the impact the addition of methyl‐lomustine would have on response, duration of survival, and survival rates in patients with advanced colorectal cancer. Methods. The methyl‐lomustine/5‐FU/Leucovorin (MFL) regimen consisted of methyl‐lomustine (110 mg/m2), administered on Day 1 of each 8‐week cycle with six weekly boluses of 5‐FU (600 mg/m2), and Leucovorin (500 mg/m2). The FL treatment arm consisted of the administration of 5‐FU and Leucovorin as described above. Patients were evaluated for response and toxicity after each 8‐week cycle. Results. Of 319 patients included in this trial, 297 (93.1%) had disease evaluable for response and toxicity: 145 received MFL, and 152 received FL. In this trial, 526 courses of MFL and 529 courses of FL were administered. Methyl‐lomustine/5‐FU/Leucovorin treatment resulted in 4 complete and 30 partial responses (response rate, 21.9%), and FL treatment resulted in 9 complete and 33 partial responses (response rate, 26.4%). There was no significant difference in median survival duration between patients in the two arms (MFL = 48 weeks, FL = 51 weeks). However, MFL was significantly more toxic with greater myelosuppression than was FL (Grade 3–4 neutropenia: MFL = 56 patients, FL = 27 patients, P < 0.001; Grade 3–4 thrombocytopenia: MFL = 49 patients, FL = 2 patients, P < 0.001; Grade 3–4 anemia: MFL = 15 patients, FL = 6 patients, P < 0.001; and more prolonged median duration of granulocytopenia: MFL = 9 days, FL = 7 days, P < 0.001; and thrombocytopenia: MFL = 14 days, FL = 7.5 days, P < 0.001). Conclusion. Because the addition of methyl‐lomustine in the MFL schedule markedly increased the toxicity of the regimen and because the FL regimen was as effective as MFL, the authors recommend that Leucovorin and 5‐FU remain the treatment choice for treating patients with metastatic colorectal cancer. Cancer 1995; 76:1709–14.

Original languageEnglish (US)
Pages (from-to)1709-1714
Number of pages6
JournalCancer
Volume76
Issue number10
DOIs
StatePublished - Nov 15 1995

Keywords

  • 5‐fluorouracil
  • colon cancer
  • folinic acid
  • methyl‐lomustine
  • nitrosoureas
  • randomized trial

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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