| Popis: |
4096 Background: FOLFOXIRI demonstrated manageable toxicities and improved activity and efficacy compared to FOLFIRI in MCRC in a phase III trial by the G.O.N.O. group. Oral C has demonstrated similar efficacy to 5-FU and might substitute 5-FU in the FOLFOXIRI regimen. Methods: The G.O.N.O. started a pilot study to evaluate the combination of escalating doses of C with fixed doses of I, O (XELOXIRI) in metastatic and not resectable CRC patients (pts). The objectives of the study are the definition of the recommended dose (RD) of C in combination with I and O, safety and activity of the combination and analysis of plasma pharmacokinetics. The planned treatment in the first 3 patients was: I 165 mg/sqm over 1-h on day 1, O 85 mg/sqm over 2-h on day 1 and C 2,500 mg/sqm/die from day 1 to 7, repeated every 2 weeks. C dose was increased to 3,000 mg/sqm/die or decreased to 2,000 mg/sqm/die in subsequent groups of 3 to 6 pts on the basis of the observed dose limiting toxicities (DLT). Results: Up today 33 patients have been enrolled. Main patients characteristic are: sex (M/F) = 22/11, PS (0/1/2) = 28/4/1, age (median/range) = 65/42–76, sites of disease (single/multiple) = 18/15. The DLT was G3–4 diarrhea that was observed in 2 out 6 patients receiving C at 2500 mg/sqm, in 2 out 3 patients receiving C at 3,000 mg/sqm and in 1 out 6 patients receiving C at 2,000 mg/sqm. This last dose was defined the RD. Among the 23 patients treated at the RD main G3–4 toxicities were: diarrhea 17%, neutropenia 26%, thrombocytopenia 9%, neurotoxicity 4%. One toxic death for diarrhea and sepsis occurred. Up today 21 out of the 23 patients (2 patients too early) treated at the RD are assessable for response (ITT analysis) and 15 RP, 3 SD and 3 treatment failures have been observed with a response rate of 71% (95% CI: 48–89%). At a median follow-up of 10.3 months median PFS is 9.0+ months and median OS isn’t yet reached. Conclusions: XELOXIRI is a feasible regimen with diarrhea being the DLT. The recommended dose of C is 2,000 mg/sqm. At the RD toxicity is manageable and preliminary results in terms of activity are promising. Partially supported by Fondazione ARCO. No significant financial relationships to disclose. |
