A meta-analysis of two randomised trials of early chemotherapy in asymptomatic metastatic colorectal cancer

Abstract

This report constitutes a prospectively planned meta-analysis combining two almost identical trials undertaken in Australasia and Canada to study the effect of starting chemotherapy immediately in asymptomatic patients with metastatic colorectal cancer. Patients (n ¼ 168) were randomised to receive either immediate or delayed treatment (at onset of predefined symptoms). Australasian patients received either weekly 5-fluorouracil and leucovorin (500 and 20 mg m À2 , respectively) (n ¼ 59) or the daily  5 Mayo Clinic schedule (425 and 20 mg m À2 , respectively) (n ¼ 42). Canadian patients were treated with the Mayo schedule (n ¼ 67). Otherwise, the two studies were almost identical in design and each used the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 instrument for measuring quality of life (QoL). Treatment was continued until 6 months had elapsed or disease progression occurred. Low accrual led to trial suspension before the predetermined sample size for either study was reached. Median survival was not significantly better with immediate treatment (median 13.0 vs 11.0 months; hazard ratio, 1.15; 95% confidence interval (CI) 0.79 -1.72; P ¼ 0.49). There was no statistically significant difference in progression-free survival (time from randomisation until first evidence of progression after chemotherapy, 10.2 vs 10.8 months; hazard ratio, 1.08; 95% CI 0.71 -1.64; P ¼ 0.73). There was no difference in overall QoL or its individual domains between the two treatment strategies at baseline or at any subsequent time point. Early treatment of asymptomatic patients with metastatic colorectal cancer did not provide a survival benefit or improved QoL compared to withholding treatment until symptoms occurred.

Current directions in chemotherapy for colorectal cancer

“…23 However, a meta-analysis of 168 patients from two randomized trials of early chemotherapy in asymptomatic metastatic CRC concluded that early treatment did not provide a survival benefit, or improve QOL, compared with delaying treatment until symptoms occurred. 24 However, some experimental studies have suggested that the curability rate of chemotherapy decreases in proportion to the tumor volume. For example, the response of lung metastases of the Lewis lung tumor to single-dose cyclophosphamide has been studied as a function of the size of the metastases.…”

Application of meta-analysis in evidence-based oncology

“…Therapy metastatic colorectal cancer were analyzed by Ackland et al [35] There was no difference in overall quality of life or its individual domains between the two treatment strategies (immediate or delayed treatment at onset of predefined symptoms) at baseline, or at any subsequent time point. Early treatment of asymptomatic patients with metastatic colorectal cancer did life compared to withholding treatment until symptoms occurred.…”

Treatment in advanced colorectal cancer: what, when and how?

“…Whereas the original Nordic study concluded that early treatment in asymptomatic patients with advanced CRC prolonged survival, asymptomatic period and time to progression (1992), a meta-analysis of two subsequent studies conducted in Canada and Australasia did not show significant improvement in survival and QoL to commence early treatment in asymptomatic patients (Ackland et al, 2005). Notably, the latter two studies terminated prematurely due to poor accrual.…”