RANDOMIZED PHASE-II STUDIES IN ADVANCED COLORECTAL-CARCINOMA - A NORTH-CENTRAL-CANCER-TREATMENT-GROUP STUDY

  • 1 January 1983
    • journal article
    • research article
    • Vol. 67  (11) , 1001-1008
Abstract
5-FU (5-fluorouracil), semustine (MeCCNU), triazinate (TZT), and razoxane (ICRF-159) have each shown activity against advanced colorectal cancer in studies by at least two investigative groups. Objective response rates, however, have been low, without evidence of increased patient survival. This study investigated whether enhanced activity might result from giving these agents in 2-drug combinations. There were 167 eligible and evaluable patients randomized among the programs: 5-FU at a dose of 500 mg/m2 per day by i.v. push .times. 5 (F); 5-FU at a dose of 400 mg/m2 per day i.v. .times. 5 plus TZT at a dose of 175 mg/m2 per day i.v. .times. 3 (FT); 5-FU at a dose of 400 mg/m2 per day plus ICRF-159 at a dose of 600 mg/m2 per day orally .times. 3 (FI); MeCCNU at a dose of 150 mg/m2 per day orally plus TZT at a dose of 200 mg/m2 per day i.v. .times. 3 (MT); MeCCNU at a dose of 150 mg/m2 orally plus ICRF-159 at a dose of 500 mg/m2 per day orally .times. 3 (MI); and ICRF-159 at a dose of 425 mg/m2 per day orally .times. 3 plus TZT at a dose of 125 mg/m2 per day i.v. .times. 3 (IT). Patients with limiting conditions (serum creatinine > 1.5 mg/dl or elevated bilirubin) were randomized among programs F, FI and MI. Objective response rates by treatment arm were: F-13% (4 of 31 patients); FT-13% (4 of 31); FI-15% (4 of 27); MT-11% (3 of 28); MI-13% (4 of 32) and IT-6% (1 of 17). Response rates of combination arms were not significantly larger than those of 5-FU alone. With regard to survival, patients initially treated with 5-FU alone had the most favorable experience (median, 10.8 mo). Multivariate analysis showed the following factors to have a significant and independent influence on survival: Eastern Cooperative Oncology Group performance score, grade, site of indicator lesion and the presence of 5-FU in the treatment regimen. Toxic effects most frequently seen were nausea, vomiting, thromobocytopenia, leukopenia, diarrhea, stomatitis, alopecia and dermatitis. The incidence and severity of toxicity were roughly comparable among the 6 treatment arms.