Uracil/ftorafur/leucovorin combined with irinotecan (TEGAFIRI) or oxaliplatin (TEGAFOX) as first-line treatment for metastatic colorectal cancer patients: results of randomised phase II study

Abstract

This randomised phase II study evaluates the safety and efficacy profile of uracil/tegafur/leucovorin combined with irinotecan (TEGAFIRI) or with oxaliplatin (TEGAFOX). One hundred and forty-three patients with measurable, non-resectable metastatic colorectal cancer were randomised in a multicentre study to receive TEGAFIRI (UFT 250 mg m À2 day days 1 -14, LV 90 mg day days 1 -14, irinotecan 240 mg m À2 day 1; q21) or TEGAFOX (UFT 250 mg m À2 day days 1 -14, LV 90 mg day days 1 -14, oxaliplatin 120 mg m À2 day 1; q21). Among 143 randomised patients, 141 were analysed (68 received TEGAFIRI and 73 TEGAFOX). The main characteristics of the two arms were well balanced. The most common grade 3 -4 treatment-related adverse events were neutropenia (13% of cases with TEGAFIRI; 1% in the TEGAFOX group). Diarrhoea was prevalent in the TEGAFIRI arm (16%) vs TEGAFOX (4%). Six complete remission (CR) and 19 partial remission (PR) were recorded in the TEGAFIRI arm (odds ratio (OR): 41.7; 95% confidence limit (CL), 29.1 -55.1%), and six CR and 22 PR were recorded in the TEGAFOX group, (OR: 38.9; 95% CL, 27.6 -51.1). At a median time follow-up of 17 months (intequartile (IQ) range 12 -23), a median survival probability of 20 and 19 months was obtained in the TEGAFIRI and TEGAFOX groups, respectively. Median time to progression was 8 months for both groups. TEGAFIRI and TEGAFOX are both effective and tolerable first-line therapies in MCRC patients. The employment of UFT/LV given in doublet combination is interesting and the presented data appear comparable to equivalent infusion regimens described in the literature. The safety profile of the two combinations also allows an evaluation with other biological agents such as monoclonal antibodies.

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

“…The results from the present study confirm that alternating irinotecan and oxaliplatin during treatment with UFT with LV allows patients to receive an effective triple-drug regimen without the excessive haematological toxicities often observed with such treatments. The combination of UFT with LV plus irinotecan and oxaliplatin was highly effective, with excellent ORRs that were consistent with the phase I study results and better than those reported for UFT with LV plus irinotecan (Mendez et al, 2005;Delord et al, 2007;Bajetta et al, 2007a) or UFT with LV plus oxaliplatin (Feliu et al, 2004;Rosati et al, 2005;Bennouna et al, 2006;Bajetta et al, 2007a), providing further support for the up-front treatment approach. Particularly notable was the fact that all patients treated at the MTD benefited from therapy, with partial responses in 68% patients and stable disease in 32%.…”

“…In addition, patients in the UFT with LV group had a significantly lower incidence of stomatitis and other gastrointestinal events than 5-FU/LV. A number of small studies have shown that UFT can be combined with oxaliplatin (Feliu et al, 2004;Rosati et al, 2005;Bennouna et al, 2006;Bajetta et al, 2007a) or irinotecan (Mendez et al, 2005;Delord et al, 2007;Bajetta et al, 2007a), both combinations being effective and well tolerated in first-line mCRC.…”

Cost-effectiveness of adjuvant chemotherapy with uracil–tegafur for curatively resected stage III rectal cancer

“…Uracil -tegafur has been approved and utilised in 31 countries from Europe and Canada to Asia, excluding the United States. Recently, several studies of combination therapies of UFT/LV in metastatic colorectal cancer have shown efficacy (Bennouna et al, 2006;Bajetta et al, 2007). Therefore, the results of this study indicating effectiveness and cost-effectiveness of UFT adjuvant therapy in rectal cancer may be useful as a reference case for the direct or indirect future examination internationally.…”

A phase I study of oral UFT/leucovorin and irinotecan, plus radiation for locally recurrent rectal cancer

“…Considering an effect of systemic chemotherapy is also required for locally recurrent rectal cancer. There are several reports investigating the systemic effects of UFT/LV/ CPT-11 in combination with chemotherapy for metastatic colorectal cancer [11][12][13][14][15] . According to these results, the response rate was almost 50%, and the progression-free survival was seven months.…”

“…Combination chemotherapy of UFT/LV plus irinotecan (CPT-11) seems to be an attractive option in the treatment of metastatic colorectal cancer, because of their ease of administration. Some phase II studies have shown that the UFT/LV/CPT-11 combination chemotherapy is effective and well tolerated for metastatic colorectal cancer [11][12][13][14][15] . Giralt et al reported a phase II trial of preoperative CRT with UFT/LV in patients with advanced rectal cancer 16) .…”