Cunningham 1998.

Methods	RCT: To compare irinotecan with supportive care alone for survival, QoL and other clinical variables in patients with metastatic colorectal cancer in whom fluorouracil had failed Duration: Patients followed until death or for at least one year, beyond one year only date of death was traced. Median follow‐up 13 months Patients in both arms received SC Journal: The Lancet 1998
Participants	Participants: metastatic colorectal cancer patients which had progressed within six months of treatment with fluorouracil Median Age (years and range): Irinotecan + SC: 59 (22‐75) SC alone: 62 (34‐75) Gender: Male/Female ratio Irinotecan + SC: 129/60 SC alone: 52/38. Performance status: WHO PS 0‐2.
Interventions	Total N = 279 T1: Irinotecan + SC (n = 189) 300 to 350mg/m2 irinotecan every three weeks with supportive care versus T2: Supportive care alone (n = 90) Ratio: 2:1
Outcomes	Overall survival (primary endpoint). Secondary objectives were impact of treatment on performance status, bodyweight, tumour‐related symptoms and QOL. T1: Overall survival was significantly better (P = 0.0001), with 1 year survival: T1: 36.2% (median survival 9.2 months) versus T2: 13.8% (median survival 6.5 months). The probability of survival 2.6 times greater in T1. The survival benefit, adjusted for prognostic factors in a multivariate analysis, remained significant (P = 0.001). T1: Survival without performance status deterioration (P = 0.0001), without weight loss of more than 5% (P = 0.018) and pain‐free survival (P = 0.003) were significantly better. Comparison of quality of life data gave the following differences for functional scale physical T1 62 versus T2 41 P < 0.001. Role T1 54 versus T2 36 P = 0.002 Cognitive T1 78 versus T2 68 P = 0.006 Social T1 59 versus T2 47 P = 0.006 Symptoms Fatigue T1 51 versus T2 61 P = 0.006 Pain T1 40 versus T2 53 P = 0.001 Dyspnoea T1 30 versus T2 39 P = 0.03 Appetite loss T1 36 versus T2 55 P < 0.001 Constipation T1 27 versus T2 40 P = 0.004 Diarrhoea T1 32 versus T2 18 P < 0.001 Time to definitive QoL deterioration was significantly longer in T1, whichever the chosen threshold for deterioration (all P values < 0.002)
Notes	Authors conclusions: Despite the side effects of treatment, patients who have metastatic colorectal cancer, and for whom fluorouracil has failed, have a longer survival, fewer tumour‐related symptoms, and better QoL when treated with irinotecan than with SC alone. Irinotecan can therefore be recommended as the standard second line therapy in colorectal cancer and as a new reference for forthcoming trials
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	D ‐ Not used