Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a Phase I study

Abstract

The feasibility of combining UFT plus leucovorin (LV) with alternating irinotecan and oxaliplatin was investigated in the first-line treatment of patients with advanced colorectal cancer. Twenty-five patients, median age 63 (range 24 -79) years, World Health Organisation performance status 0 -2 and median four marker lesions, received irinotecan 180 mg m À2 on day 1, oxaliplatin 85 -100 mg m À2 on day 15 and UFT 200 -300 mg m À2 day À1 with LV 90 mg day À1 , days 1 -21 of a 28-day cycle. Patients were treated in cohorts of three. At the highest dose (irinotecan 180 mg m À2 , oxaliplatin 100 mg m À2 and UFT 300 mg m À2 day À1 ), three of four patients experienced grade 3 toxicity. Diarrhoea, lethargy and vomiting were dose-limiting. Three of nine patients had grade 2 toxicities at the maximum tolerated dose (irinotecan 180 mg m À2 , oxaliplatin 100 mg m À2 and UFT 250 mg m À2 day À1 ). There were no grade 3 toxicities in the first month of therapy. The overall response rate was 71% in 21 evaluable patients; progression-free survival was 8.8 months. Alternating irinotecan and oxaliplatin plus UFT is an effective and well-tolerated first-line treatment for patients with advanced colorectal cancer. We recommend a dose of irinotecan 180 mg m À2 on day 1, oxaliplatin 100 mg m À2 on day 15 and UFT 250 mg m À2 day À1 with LV 90 mg day À1 on days 1 -21 of a 28-day cycle for future studies.

Phase II study of UFT with leucovorin and irinotecan (TEGAFIRI): first-line therapy for metastatic colorectal cancer

“…In that study, an ORR of 58.5%, median overall survival of 17.3 months and median TTP of 8.8 months were reported. Similarly, Sheikh et al reported promising results in a phase I study of alternating UFT -oxaliplatin and UFT -irinotecan in the first-line treatment of patients with mCRC (Sheikh et al, 2007). A response rate of 71% was reported in 25 patients, with a median TTP of 8.8 months.…”

‘Liver First’ Approach in the Treatment of Colorectal Cancer with Synchronous Liver Metastases

“…The use of triple associations with irinotecan, oxaliplatin and 5-FU-LV further increased the efficacy of systemic chemotherapy. Response rates as high as 70% were obtained in 3 different studies and the overall median survival improved to 26 months [3,4,5]. The more recent development of 2 monoclonal antibodies, cetuximab (Erbitux®), a monoclonal antibody against the epidermal growth factor receptor, and bevacizumab (Avastin®), a humanized antibody against the vascular endothelial growth factor [6, 7], has improved the response rates even further.…”

Alternating irinotecan with oxaliplatin combined with UFT plus leucovorin (SCOUT) in metastatic colorectal cancer

“…We hypothesised that alternating oxaliplatin and irinotecan would allow patients to benefit from concurrent treatment with all three drugs as soon as they were diagnosed with metastatic disease, while allowing them to recover from adverse events associated with each drug before it was administered again. Results from the phase I study have been published in full (Sheikh et al, 2007). Here we present results for the expanded group of patients treated at the maximum tolerated dose (MTD) and overall results from the phase I/II study.…”

“…Inclusion and exclusion criteria have been described previously (Sheikh et al, 2007). In brief, patients were aged X18 years, had no prior chemotherapy for metastatic disease and a World Health Organization performance status of 0 -2.…”

“…Serum tumour carcinoembryonic antigen (CEA) measurements were performed monthly if raised at baseline. Toxicities were recorded at 2-weekly visits according to the National Cancer Institute Common Toxicity Criteria (version 2) and the dose-limiting toxicities at 1 month, that is, diarrhoea, lethargy and vomiting, used to decide the dose escalation schedule during the phase I study, as reported previously (Sheikh et al, 2007).…”