1. ¹Australasian Gastro-Intestinal Trials Group and NSW Clinical Oncology Group, Locked Bag 77, Camperdown, NSW 1450, Australia
2. ²Newcastle Mater Misericordiae Hospital, Locked Bag 7, Hunter Region Mail Centre, NSW 2310, Australia
3. ³National Health and Medical Research Council, Locked Bag 77, Camperdown, NSW 1450, Australia
4. ⁴National Cancer Institute of Canada Clinical Trials Group, 10 Alcorn Avenue, Suite 200, Toronto, Ontario, Canada M4V 381
5. ⁵Princess Margaret Hospital, 610 University Avenue, Toronto, Canada MSG 2M9
6. ⁶North Central Cancer Treatment Group, Operations Office, 200 First Street SW, Rochester, MN 55905, USA
7. ⁷Department of Medical Oncology, Northern Rivers Area Health Services, Tweed Hospital, Powell Street, Tweed Heads, NSW 2485, Australia

Correspondence: Dr SP Ackland, Department of Medical Oncology, Newcastle Mater Misericordiae Hospital, Locked Bag 7, Hunter Region Mail Centre, Newcastle, NSW 2310, Australia. E-mail: Stephen.Ackland@newcastle.edu.au

Received 7 March 2005; Revised 5 September 2005; Accepted 27 September 2005; Published online 1 November 2005.

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=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^-2, respectively) (n=59) or the daily 5 Mayo Clinic schedule (425 and 20 mg m^-2, respectively) (n=42). Canadian patients were treated with the Mayo schedule (n=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=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=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.