Even Patients With Localised Colorectal Cancer Benefit From Chemotherapy After Surgery

Main Category: Colorectal Cancer
Also Included In: Cancer / Oncology
Article Date: 09 Jan 2008 - 15:00 PDT

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Patients with stage II colon cancer, for whom there is ambiguous evidence about whether or not they should receive chemotherapy, survive longer if treated with fluorouracil and folinic acid than if they undergo surgery alone, according to the results of a prospective randomised trial.

Cytotoxic chemotherapy is known to lower the risk of recurrence in patients with extensive disease who have undergone curative resection for colorectal cancer. However, there is some doubt over whether the benefit is sufficient to justify the toxic side-effects in patients whose risk of recurrence is considered low, ie, those in which there is tumour penetration through the bowel wall but no involvement of regional lymph nodes or distant metastases (stage II disease).

To investigate this issue in a real-world setting, and test which chemotherapy regimen might yield the greatest benefit, the Quasar---QUick And Simple And Reliable---trial enrolled a large group of patients with colorectal whom their local physicians described as having an "uncertain indication" for chemotherapy due to their localised disease. For the study, 3239 patients were recruited from 19 countries between May 1994 and December 2003, part of a larger population of 7559 patients who underwent surgery and were assessed by their clinicians as having either a clear or uncertain indication for chemotherapy; those with a certain indication were reported elsewhere. Patients were only eligible if they had no evidence of distant metastases and no contraindications to chemotherapy.

After the patients had undergone attempted curative resections and agreed to enrolment in the trial, they were randomised to receive either chemotherapy with fluorouracil and folinic acid or to observation alone. Those assigned to the chemotherapy group before October 1997 were further divided between regimens: fluorouracil plus either high-dose or low-dose folinic acid, each combined with levamisole or placebo. Patients in the chemotherapy group after 1997 all received fluorouracil plus low-dose folinic acid in 30 doses. The reason for this change was that in the early 1990s a 1-year course of fluorouracil plus levamisole was the standard treatment for colon cancer, but it was later shown that a 6-month regimen of fluorouracil with folinic acid was at least as effective. All other aspects of patient management were left to the discretion of each patient's physician, including whether or not to administer radiotherapy for those with rectal cancers.

To keep things as simple as possible for the physicians participating in the trial, the study organisers decided that follow up would be limited to a yearly form with basic details for each patient, with a postal follow up of the status of all patients in January 2004. The primary outcome for the trial was all cause mortality.

Over the whole study period, there were 311 deaths and 293 recurrences in the chemotherapy group and 370 and 359 deaths and recurrences, respectively, in the observation group. The relative risk of dying from any cause with chemotherapy versus observation was 0•82 (95% CI 0•70-0•95; p=0•008), meaning that chemotherapy reduced this risk by almost 20%. For recurrence, the relative risk in chemotherapy group versus observation was 0•78 (95% CI 0•67-0•91; p=0•001).

Toxic effects including diarrhoea, nausea, vomiting, mouth pain, fatigue, appetite loss, and social functioning were all significantly worse in those patients in the chemotherapy group than in those in the observation group, but only during chemotherapy.

The authors conclude that, relative to observation alone, adjuvant chemotherapy with fluorouracil and folinic acid lowers the risk of all-cause mortality in patients with colorectal cancer who have an uncertain indication for chemotherapy after surgery. They comment: "Although this improvement was of borderline statistical significance, the survival benefit is supported by a significant reduction in recurrence [and suggests that] the proportional reductions in mortality and recurrence from adjuvant chemotherapy based on fluorouracil are much the same in patients with stage II and III disease."

"The small but definite benefit from well-tolerated chemotherapy found here should provide helpful new information for discussions between patients and physicians on the potential benefits of chemotherapy and allow the patient to make a better informed decision to proceed with, or refuse, the offer of chemotherapy," note the authors.

The QUASAR Collaborative Group. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study.
Lancet 2007; 370: 2020-29.

Linked Comment:
Adjuvant chemotherapy of colorectal cancer.
Cunningham D, Starling N. Lancet 2007; 370: 1980-81

This summary is provided by the Cancer Media Service which is operated by The European School of Oncology.

http://www.cancerworld.org/mediaservice