We have previously shown that OXA may be safely combined with infusional fluorouracil (FU) and preoperative pelvic RT resulting in high rates of pathological complete responses (pCRs) in patients with LARC. Replacing infusional FU with an oral fluoropyrimidine might increase patient's convenience and eliminate the catheter-related complications of this regimen. Methods: Between June 2002 and May 2008, 21 patients (16 males, 5 females; median age 62, range 33-75 years) with LARC (cT3-T4 and/or N+; one patient also had a potentially resectable liver metastasis) were accrued in a phase I study. The aim was to define the maximum tolerated dose (MTD) of UFT (200-250-300-350 mg/m2/day, Monday through Friday for all the duration of RT) combined with a fixed weekly dose of OXA (60 mg/m2) and pelvic RT (50.4 Gy-28 fractions). Oral LV (90 mg/day, fixed dose) was administered with the same schedule as UFT. Results: UFT has been escalated up to 350 mg/m2/day without reaching the MTD. Further escalation was not planned as this corresponds to a standard monotherapy dose in advanced colon cancer. No grade III-IV toxicity was observed. One patient treated at the second dose level (UFT 250 mg/m2/day; n=6) discontinued treatment due to protracted severe obtundation after completing 5 weeks of chemoradiation. All the other patients completed RT as planned while 4 did not receive all the planned chemotherapy because of toxicity (n=3) or refusal (n=1). Only 4 of 126 weekly courses of UFT/OXA chemotherapy were omitted and 3 were delayed. Two patients were not operated due to extrapelvic progression while one patient with a clinical complete response refused surgery. Among 18 operated patients, 9 had a major down-staging (ypT0-2 pN0) with 4 pCRs (2 of them among the 6 patients treated at the highest dose level). Conclusions: Oral UFT may replace infusional FU in combination with weekly OXA and standard pelvic RT with low toxicity and promising activity.
A phase I study of uracil/tegafur (UFT) and oral leucovorin (LV) + weekly oxaliplatin (OXA) and preoperative radiotherapy (RT) in locally advanced rectal cancer (LARC)
DE CIAN, FRANCO;
2004-01-01
Abstract
We have previously shown that OXA may be safely combined with infusional fluorouracil (FU) and preoperative pelvic RT resulting in high rates of pathological complete responses (pCRs) in patients with LARC. Replacing infusional FU with an oral fluoropyrimidine might increase patient's convenience and eliminate the catheter-related complications of this regimen. Methods: Between June 2002 and May 2008, 21 patients (16 males, 5 females; median age 62, range 33-75 years) with LARC (cT3-T4 and/or N+; one patient also had a potentially resectable liver metastasis) were accrued in a phase I study. The aim was to define the maximum tolerated dose (MTD) of UFT (200-250-300-350 mg/m2/day, Monday through Friday for all the duration of RT) combined with a fixed weekly dose of OXA (60 mg/m2) and pelvic RT (50.4 Gy-28 fractions). Oral LV (90 mg/day, fixed dose) was administered with the same schedule as UFT. Results: UFT has been escalated up to 350 mg/m2/day without reaching the MTD. Further escalation was not planned as this corresponds to a standard monotherapy dose in advanced colon cancer. No grade III-IV toxicity was observed. One patient treated at the second dose level (UFT 250 mg/m2/day; n=6) discontinued treatment due to protracted severe obtundation after completing 5 weeks of chemoradiation. All the other patients completed RT as planned while 4 did not receive all the planned chemotherapy because of toxicity (n=3) or refusal (n=1). Only 4 of 126 weekly courses of UFT/OXA chemotherapy were omitted and 3 were delayed. Two patients were not operated due to extrapelvic progression while one patient with a clinical complete response refused surgery. Among 18 operated patients, 9 had a major down-staging (ypT0-2 pN0) with 4 pCRs (2 of them among the 6 patients treated at the highest dose level). Conclusions: Oral UFT may replace infusional FU in combination with weekly OXA and standard pelvic RT with low toxicity and promising activity.
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