Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer

• Published in: Journal of clinical oncology Vol. 16; no. 1; p. 295
• Main Authors: O'Connell, M J, Laurie, J A, Kahn, M, Fitzgibbons, Jr, R J, Erlichman, C, Shepherd, L, Moertel, C G, Kocha, W I, Pazdur, R, Wieand, H S, Rubin, J, Vukov, A M, Donohue, J H, Krook, J E, Figueredo, A
• Format: Journal Article
• Language: English
• Published: United States 01.01.1998
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Adjuvants, Immunologic - administration & dosage; Adolescent; Adult; Aged; Aged, 80 and over; Antidotes - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Chemotherapy, Adjuvant; Colonic Neoplasms - drug therapy; Colonic Neoplasms - mortality; Colonic Neoplasms - pathology; Colonic Neoplasms - surgery; Female; Fluorouracil - administration & dosage; Humans; Leucovorin - administration & dosage; Levamisole - administration & dosage; Male; Middle Aged; Neoplasm Staging; Prospective Studies
• ISSN: 0732-183X
• DOI: 10.1200/JCO.1998.16.1.295

This study had two major goals: (1) to assess the effectiveness of a regimen of fluorouracil (5-FU) plus levamisole plus leucovorin as postoperative surgical adjuvant therapy for patients with high-risk colon cancer, and (2) to evaluate 6 months versus 12 months of chemotherapy. Patients with poor-prognosis stage II or III colon cancer were randomly assigned to receive adjuvant chemotherapy with either intensive-course 5-FU and leucovorin combined with levamisole, or a standard regimen of 5-FU plus levamisole. Patients were also randomly assigned to receive either 12 months or 6 months of chemotherapy, which resulted in four treatment groups. Eight hundred ninety-one of 915 patients entered (97.4%) were eligible. The median follow-up duration is 5.1 years for patients still alive. There was a difference among the four treatment groups with respect to patient survival, and a significant duration-by-regimen interaction was observed. Specifically, standard 5-FU plus levamisole was inferior to 5-FU plus leucovorin plus levamisole when treatment was given for 6 months (5-year survival rate, 60% v 70%; P < .01). There was no significant improvement in patient survival when chemotherapy was given for 12 months compared with 6 months. When chemotherapy was given for 6 months, standard 5-FU plus levamisole was associated with inferior patient survival compared with intensive-course 5-FU plus leucovorin plus levamisole. These data suggest that 5-FU plus levamisole for 6 months should not be used in clinical practice, whereas 6 months of treatment with 5-FU plus leucovorin plus levamisole is effective.