• I Popov, S Jelić, D Radosavljević, and Z Nikolić-Tomasević.
• Institut za onkologiju i radiologiju Srbije. ipopov@ncrc.ac.yu
• Srp Ark Celok Lek. 1998 Nov 1; 126 (11-12): 506-11.

AbstractThe benefit of adjuvant therapy in colorectal cancer (CRC) has been provided in clinical studies that have demonstrated reduction of up to 30% in a 5-year overall mortality in patients (pts.) with TNM stage III (Dukes' stage C) carcinoma. Patients with metastatic CRC are usually in a relatively good condition despite their advanced disease. Therefore, some clinicians wished to withheld the toxicity of chemotherapy until the disease became symptomatic. Others, however, felt it appropriate to treat patients early in the course of the disease. Four clinical trials may be cited addressing this clinical uncertainty (Table 1). Patients receiving chemotherapy had a significantly longer median survival in comparison with only best supportive care. The delay of the carrying out of systemic chemotherapy in patients with metastatic disease decreases the symptom free interval (2 vs. 10 months, p < 0.001), time to disease progression (3 vs. 8 months, p < 0.001) and median survival (14 versus 9 months, p < 0.02) compared to an early start of therapy [7C. Patients with metastatic colorectal cancer benefit from early chemotherapy in terms of survival and quality of life. It is clear that survival is determined by prognostic factors, mainly the performance status, which is a highly significant predictor of therapeutic response and overall survival in advanced colorectal cancer patients. Some authors suggests that the response is a potent and independent prognostic factor of survival, and that response can be used as surrogate marker of survival. Stable disease is a category in therapy response evaluation which is not included in the overall response rate. In many studies with a response rate below 20%, chemotherapy almost doubles the survival of patients. In most chemotherapy trials in advanced colorectal cancer patients, about 30-50% had stable disease. One of the possible reasons may be that in colorectal cancer stabilization of disease is a clinically relevant effect of chemotherapy. If we accept that disease stabilization is a clinically relevant effect of chemotherapy, should we continue with chemotherapy after 3 or 4 courses, and for how long, or should we stop treatment according to rules for stable disease, i.e. following 4 courses? The results of on study, which we performed in 99 patients with advanced colorectal cancer, indicate that under category of "stable disease" there are two different subpopulations of patients with quite different symptom responses as an effect of chemotherapy, different time to progression and possible different survival (Graph 1 and Graph 2). It seems that stable disease patients with clinical benefit could be a target group for policy "to treat until disease progression". The tumour response is likely to be positively correlated with improvement in quality of life when a patient is a symptomatic from cancer before the treatment. Stable disease patients without symptom improvement have no benefit from further chemotherapy and in these patients treatment should be stopped. Such selection would spare from toxicity stable disease patients without clinical benefit. We have no data whether different number of chemotherapy cycles in the groups of patients with and without clinical benefit could lead to a bias in survival estimation. Patients who achieved also a stable disease, but who were asymptomatic from the beginning of chemotherapy, and who are still asymptomatic after 4 chemotherapy courses, make a group for which is hard to make decision either to continue or to stop chemotherapy. We have treated and followed-up these stable disease patients as patients without clinical benefit. We have no answer if they could reach better time to progression and/or survival if they had been treated for more than 4 courses. Careful studies in the evaluation of the quality of life in connection with treatment effects for all stable disease subpopulations of patients are warranted. (ABSTRACT TRUNCATED)

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