Concurrent modulation of 5-fluorouracil with methotrexate and L- leucovorin: An effective and moderately toxic regimen for the treatment of advanced colorectal carcinoma a multicenter phase II study of the southern Italy cooperative oncology group

Pasquale Comella, Vito Lorusso, Rossana Casaretti, Luigi De Lucia, Giacomo Cartenì, Luigi Manzione, Sergio Mancarella, Mario De Lena, Giuseppe Comella

Research output: Contribution to journalArticle


Aims and background: Methotrexate (MTX) and leucovorin (LV) can enhance the cytotoxicity of 5-fluorouracil (5FU) by modifying its metabolic pathway inside target cells. Some preclinical studies and clinical trials have suggested that the concurrent or sequential double modulation of 5FU by means of MTX and LV may give a higher activity than single biochemical modulations. The purpose of our phase II study was to assess the activity and toxicity of a biweekly regimen including MTX, levo-LV and 5FU in colorectal cancer patients. Methods: From July 1994 to May 1997, 100 consecutive patients affected by advanced or metastatic colorectal carcinoma were given MTX, 750 mg/m2 iv (2-h infusion) on day 1, and levo-LV, 250 mg/m2 iv (2-h infusion) followed by 5FU, 800 mg/m2 iv bolus on day 2, every two weeks. Patients were treated until complete response or progressive disease was documented, or for a maximum of 16 courses. Results: Among 97 eligible patients, 5 complete and 25 partial responses were obtained, giving an overall response rate of 31% (95% exact confidence limits, 22-41%). Response rate was significantly higher in patients with a good (ECOG scale 0) than with a poor (ECOG scale 1 or 2) performance status (40% versus 17%, P

Original languageEnglish
Pages (from-to)465-472
Number of pages8
Issue number6
Publication statusPublished - Nov 1999



  • 5FU modulation
  • Colorectal carcinoma
  • MTX + 5FU + LV regimen

ASJC Scopus subject areas

  • Cancer Research

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