Patupilone in patients with pretreated metastatic/locally recurrent colorectal cancer: results of the Phase II CINATRA trial
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Background Phase I trials of the microtubule stabilising agent patupilone showed encouraging tumour control and response rates in patients with metastatic colorectal cancer. Methods Patients with metastatic or locally recurrent colorectal cancer who had progressed following treatment with oxaliplatin, irinotecan and fluoropyrimidines were treated with patupilone (8 mg/m2 IV every 3 weeks) in combination with dexamethasone or prednisolone. Results The trial was closed early after 29 patients had been enrolled due to concerns about toxicity. 20 patients (71.4 %) experienced at least one grade 3–5 toxicity, most commonly diarrhoea (14 patients), dehydration (7 patients) and lethargy (6 patients). The 12 week progression-free survival rate was 16.7 % (95 % CI 6.1 %–36.5 %) in the 24 patients with a 12 week scan available or who had died prior to the 12 week scan. No complete or partial responses were seen by 12 weeks. The median progression-free survival was 2.6 months (95 % CI 2.3–2.9) and median overall survival was 6.1 months (95 % CI 3.7–8.4). Conclusion Patupilone given at a dose of 8 mg/m2 IV over 20 min every 3 weeks was associated with high levels of toxicity and no significant evidence of efficacy in patients with pre-treated colorectal cancer.
KeywordsPatupilone Colorectal cancer Toxicity Diarrhoea
We acknowledge National Health Service funding to the National Institute for Health Research Biomedical Research Centre and Novartis who provided an educational grant and patupilone.
The study was approved by a Research Ethics Committee and all patients provided written informed consent.
Conflicts of interest
IC has received research funding from Novartis, Merck-Serono and Roche, and has advisory roles (compensated) with Roche, Sanofi-Aventis, Novartis and Eli Lilly. DC has received research funding from Amgen, Roche, Sanofi-Aventis, Merck-Serono, Novartis, and Celgene, and has had advisory roles (uncompensated) with Roche and Amgen. SR has received research funding from GlaxoSmithKline and has advisory roles (uncompensated) with Roche, Sanofi-Aventis, Merck-Serono and Celgene. CS sat on a global advisory board for Novartis 3 years ago and receives research funding from Novartis. SYM, CP, KLY, AW, CJ, GS, JW, GSm and AG have no conflicts of interest to declare.
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