Adjuvant chemotherapy in colorectal cancer: A joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group

Abstract

Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to+/-levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations.

HER3 expression is correlated to distally located and low-grade colon cancer

“…As a result of representative tumor material, reviewed by an affiliated pathologist and a well working antibody SP71 (ErbB, ab 93739), the staining resulted in very few IHC failures. The 521 patients were not expected to differ from the colon cancer cohorts in other Nordic countries regarding age, gender and treatment [10]. However, an overweight of stage III patients were known in our material compared to the Nordic trials.…”

“…In the adjuvant study from which our subgroup of patients originated, the survival benefit of chemotherapy did not reach statistical significance [10].…”

“…The last patient update was in November 2004. Surgical specimens were derived from adjuvant Nordic trials, where patients (75 years) with CRC of stage II and III were randomized to either surgery or surgery plus 5 fluorouracil (5-FU) based adjuvant chemotherapy [10]. The 521 patients were a part of the Swedish cohort of colon cancer patients in the Nordic trials.…”

Metastatic lymph node ratio in stage III rectal cancer; prognostic significance in addition to the 7th edition of the TNM classification

“…However, as in colon cancer, distant recurrences are still a matter of concern and occur in 25-30% of patients at five years (6). Adjuvant chemotherapy can possibly aid, but there is still no strong evidence that its benefits in rectal cancer are comparable to those in colon cancer patients (7)(8)(9)(10). Although there are some studies that show a minor benefit of adjuvant chemotherapy in rectal cancer patients (11-13) a recent European consensus conference failed to reach consensus on its use (14).…”

Curative Strategies for Liver Metastases from Colorectal Cancer: A Review

“…There is evidence that recurrence rates are worse, and possibly similar to those seen with observation alone, if there is a delay Ͼ8 weeks in starting adjuvant chemotherapy after resection of a colonic primary without metastases [82]. This suggests that a simultaneous procedure may be preferential in those who are planned to have adjuvant chemotherapy, because a staged procedure would cause a substantial delay in starting chemotherapy.…”