Sequential Treatment with High-Dose Methotrexate and Fluorouracil in Advanced Colorectal Cancer. Experience of The Southern Italian Oncology Group (GOIM)

Summary

A total of 101 patients with advanced colorectal cancer in two consecutive Southern Italian Oncology Groups (GOIM) studies (8501 and 8801- arm A) were treated with a sequential combination of high dose methotrexate (HDMTX) and fluorouracil (FU). Of the 92 eligible patients, 2 achieved complete response (2%) and 27 partial response (30%), with a median duration of 7 months. When classified according to the time interval between administration of the two drugs, retrospective analysis showed significant improvement (p = 0.04) in overall survival in the shorter time interval group (6 hours). The observed toxicities were generally mild and transient. Our data confirm the efficacy of the synergism between the two chemotherapeutic agents, in particular when administered with a 6-hour interval. Further studies are necessary to establish the possibility of enhancing the efficacy of sequential treatment with the modulation of FU with high-dose folinic acid.

Key Words:

• advanced colorectal cancer
• 5FU biochemical modulation
• MTX-5FU sequence.