Colorectal cancer

Abstract

The report on colorectal cancer by R Midgley and D Kerr1Midgley R Kerr D Colorectal cancer.Lancet. 1999; 353: 391-399Summary Full Text Full Text PDF PubMed Scopus (387) Google Scholar is a well-researched and comprehensive review of colorectal cancer, that provides current, state-of-the-art information about the disease. I, however, strongly disagree with their statement about systemic chemotherapy in the adjuvant therapy of rectal cancer. They state that there is current controversy about the efficacy of adjuvant chemotherapy in rectal and Dukes B colon cancers. I agree with them about the absence of evidence regarding overall survival benefit with adjuvant therapy in Dukes B (American Joint Committee on Cancer Staging [AJCC] stage II) colon cancer.2Moertel CG Fleming TR Macdonald JS et al.Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer.J Clin Oncol. 1995; 13: 2936-2943Crossref PubMed Scopus (329) Google Scholar There is, however, strong evidence that adjuvant chemotherapy in combination with radiotherapy improves disease-free and overall survival in rectal cancer. The study by Gastrointestinal Tumor Study Group showed a significant disease-free survival advantage (54% vs 27%, p=0·005) in patients who received postoperative combined modality therapy with radiation plus 5-fluorouracil and methyl-N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea.3Gastrointestinal Tumor Study Group Prolongation of the disease free interval in surgically treated rectal carcinoma.N Engl J Med. 1985; 312: 1465-1472Crossref PubMed Scopus (1204) Google Scholar The North Central Cancer Treatment Group reported a 46% reduction in local recurrence and 37% reduction in distant metastases with postoperative radiotherapy and systemic 5-fluorouracil-based chemotherapy in patients who had undergone surgical resection of their Dukes stage BII and C rectal cancer.4Krook JE Moertel CG Gunderson LL et al.Effective surgical adjuvant therapy for high risk rectal carcinoma.N Engl J Med. 1991; 324: 709-715Crossref PubMed Scopus (1654) Google Scholar This trial also showed a 36% reduction in the rate of cancer-related deaths. There have been several additional studies that have shown similar benefit with adjuvant chemotherapy in high-risk rectal cancer. The real controversy lies in the optimum schedule and modulation of 5-fluorouracil in adjuvant therapy for rectal cancer. Initial results of Intergroup trial 0114 revealed no additional benefit with the addition of levamisole to 5-fluorouracil and radiation therapy and the investigators concluded that further follow-up was required before a definitive role of addition of folinic acid could be determined. O'Connell and colleagues showed that protracted infusion of 5-fluorouracil during radiation therapy resulted in improved disease-free and overall survival when compared with bolus 5-fluorouracil.5O'Connell MJ Martenson JA Weiand HS et al.Improving adjuvant therapy for rectal cancer by combining protracted infusion fluorouracil with radiation therapy after curative surgery.N Engl J Med. 1994; 331: 502-507Crossref PubMed Scopus (1055) Google Scholar These phase three randomised trials established that 5-fluorouracil-based chemotherapy in combination with pelvic radiation therapy should be the standard of practice in surgically resected Dukes stage BII and C (AJCC stages II and III) rectal cancer.