Adjuvant Chemotherapy for Stage II Colon Cancer: Less Complicated Than We Thought

Abstract

TO THE EDITOR: In his recent editorial, Mayer agreed with the conclusion of Tournigand et al that there is no benefit for the inclusion of oxaliplatin in adjuvant chemotherapy regimens for patients with standard or indeed high-risk stage II colon cancer. Mayer then posed the question as to whether these patients, with a generally favorable prognosis, merit any adjuvant treatment at all. The virtues of prolonged clinical trial follow-up to provide mature survival data were extolled, but it surprised us greatly that no mention was made of Quasar (Quick and Simple and Reliable) 1 (A UKCCR[United Kingdom Coordinating Committee on Cancer Research] Study of Adjuvant Chemotherapy for Colorectal Cancer), the only trial in this field to show a survival benefit for patients with stage II colon cancer. In the Quasar 1 study, 2,291 patients with colon cancer were randomly assigned to receive chemotherapy with fluorouracil and leucovorin or to undergo observation. After a median follow-up of 5.5 years, the trial demonstrated that although the absolute improvements are small, the relative risk of death that was observed translates into a significant absolute improvement in survival of 3.6% (95% CI, 1.0 to 6.0; P .04). This is by far the largest and therefore the most informative trial of chemotherapy ever undertaken for this disease, and it is the only trial to show a significant survival benefit. The fluorouracil-based chemotherapy was well tolerated, and we believe that these results are sufficient to mandate an informed discussion with all patients with stage II colon cancer so that at least the offer of treatment might be made. Furthermore, we have worked with colleagues from the National Surgical Adjuvant Breast and Bowel Project, the Cleveland Clinic, and Genomic Health to develop a polymerase chain reaction– based prognostic gene signature that has now been validated in more than 5,000 patients. This can be used to define the risk of recurrence with greater precision than conventionally accepted high-risk criteria, and therefore can inform and influence the outcome of the physicianpatient consultation. We believe that there are data and validated tools that support rational and informed decision making on the utility of adjuvant fluorouracil-based therapy for patients with stage II colon cancer, and that matters are not necessarily as nihilistic as Mayer implies.