Prognostic factors for tumour response, progression-free survival and toxicity in metastatic colorectal cancer patients given irinotecan (CPT-11) as second-line chemotherapy after 5FU failure

Our purpose was to determine, in patients with metastatic colorectal carcin oma treated with irinotecan single-agent after 5-FU failure, the most signi ficant predictive parameters for tumour response, progression-free survival and toxicity. Between October 1992 and April 1995, 455 patients with 5-FU resistant metastatic colorectal carcinoma entered four consecutive phase II trials. The first two studies assessed tumour response, the other two were randomized studies which assessed the efficacy of racecadotril to prevent irinotecan-induced diarrhoea. Due to homogeneous main eligibility criterias , data from those studies could be pooled for statistical analysis. Potenti al clinical and biological predictive factors (PF) for toxicity, tumour gro wth control, e.g. response or stabilization and progression-free survival ( PFS), were studied in multivariate analysis. 363 patients were evaluable fo r response, 432 were evaluable for PFS, 368 for neutropenia and 416 for del ayed diarrhoea, respectively. Normal baseline haemoglobin level (Hb), time since diagnosis of colorectal carcinoma, grade 3 or 4 neutropenia or diarrh oea at first cycle and a low number of organs involved were the most PF for tumour growth control (P < 0.05). Significant prognostic variables for PFS were WHO Performance Status, liver and lymph-node involvement, time since diagnosis, age and CEA Value (P less than or equal to 0.02). Six groups of patients based on the number of unfavourable prognostic factors are present ed. Baseline bilirubin, haemoglobin level, number of organs involved and ti me from diagnosis were PF for neutropenia; PS, serum creatinine, leukocyte count, time from 5-FU progression and prior abdominopelvic irradiation were PF for delayed diarrhoea (P less than or equal to 0.05). These PF should h elp clinicians to anticipate for a given patient the probability to observe a response/stabilization or a toxicity. These results should also be prosp ectively confirmed in ongoing or future trials using irinotecan, both as a single agent and in combination with other drugs. (C) 2000 cancer Research Campaign.