EXPECTANCY OR PRIMARY CHEMOTHERAPY IN PATIENTS WITH ADVANCED ASYMPTOMATIC COLORECTAL-CANCER - A RANDOMIZED TRIAL

Purpose: The advantage of chemotherapy in asymptomatic patients with advanced colorectal cancer is debatable. Whether early chemotherapy improves survival and the length of the symptom-free period versus no therapy until symptoms appear was studied in a randomized trial. Patients and Methods: A total of 183 patients with advanced, but asymptomatic colorectal cancer were randomly allocated to receive either initial treatment with sequential methotrexate 250 mg/m2 during the first 2 hours, and fluorouracil (5-FU) 500 mg/m2 at hours 3 and 23 followed by leucovorin rescue initiated at hour 24 (MFL) for 12 courses or to primary expectancy with chemotherapy not considered until symptoms appeared. One patient was ineligible and excluded from analysis. Nine patients did not fulfill the inclusion criteria and five patients refused treatment allocation; these patients were not excluded from the study population so as not to introduce bias. So far, 51 of 90 (60%) patients in the expectancy group have received chemotherapy. Results: Overall survival was better in the MFL group than in the expectancy group (Breslow-Gehan, P < .02; log-rank, P = .13) with a difference in median survival of approximately 5 months. Also the symptom-free period and the time to disease progression were longer in the MFL group (P < .001), with median differences of 8 and 4 months, respectively. Toxicity to MFL treatment was low; however, three patients died because of toxicity - none of them should have received therapy because of poor performance or S-creatinine elevation. The patients maintained an excellent performance throughout the MFL treatment unless the disease was progressive. Conclusion: We concluded that early treatment with MFL in asymptomatic patients with advanced colorectal cancer prolongs survival, the asymptomatic period, and the time to disease progression by approximately 6 months over primary expectancy. © 1992 by American Society of Clinical Oncology.