Regular Article

British Journal of Cancer (2000) 83, 431–437. doi:10.1054/bjoc.2000.1303 www.bjcancer.com
Published online 25 July 2000

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

G Freyer1, P Rougier2, R Bugat3, J-P Droz4, M Marty5, H Bleiberg6, D Mignard7, L Awad7, P Herait7, S Culine8, V Trillet-Lenoir1 and the CPT-11 F205, F220, F221 and V222 study groups

  1. 1Medical Oncology Unit and EA 643, Centre Hospitalier Lyon-Sud, 69495 Pierre-Bénite Cedex, Lyon, France
  2. 2Institut Gustave Roussy, Villejuif and Hôpital Ambroise Paré, Boulogne, France
  3. 3Institut Claudius Regaud, Toulouse, France
  4. 4Centre Léon Bérard, Lyon, France
  5. 5Hôpital Saint-Louis, Paris, France
  6. 6Institut Jules Bordet, Brussels, Belgium
  7. 7Rhone-Poulenc Rorer, Antony, France
  8. 8Centre Anticancéreux du Val d'Aurelle, Montpellier, France

Received 31 August 1999; Revised 24 March 2000; Accepted 13 April 2000.

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Abstract

Our purpose was to determine, in patients with metastatic colorectal carcinoma treated with irinotecan single-agent after 5-FU failure, the most significant 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. Potential clinical and biological predictive factors (PF) for toxicity, tumour growth control, e.g. response or stabilization and progression-free survival (PFS), were studied in multivariate analysis. 363 patients were evaluable for response, 432 were evaluable for PFS, 368 for neutropenia and 416 for delayed diarrhoea, respectively. Normal baseline haemoglobin level (Hb), time since diagnosis of colorectal carcinoma, grade 3 or 4 neutropenia or diarrhoea 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 (Pless than or equal to 0.02). Six groups of patients based on the number of unfavourable prognostic factors are presented. Baseline bilirubin, haemoglobin level, number of organs involved and time 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 (Pless than or equal to 0.05). These PF should help clinicians to anticipate for a given patient the probability to observe a response/stabilization or a toxicity. These results should also be prospectively confirmed in ongoing or future trials using irinotecan, both as a single agent and in combination with other drugs. © 2000 Cancer Research Campaign

Keywords:

irinotecan, colorectal cancer, prognostic factors, survival, toxicity

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