Purpose: To prospectively compare the rates of pathologic response, acute toxicity, and sphincter preservation with two different schedules of preoperative chemoradiotherapy in patients with cT3 mid-distal rectal cancer. Methods and Materials: Patients with cT3 and/or N+ resectable rectal carcinoma were randomized to receive one of the two following chemoradiotherapy regimens: cisplatin, 5-fluorouracil, and radiotherapy (PLAFUR) or raltitrexed, oxaliplatin, and radiotherapy (TOMOX-RT). For PLAFUR, cisplatin (60 mg/m2) was given on Days 1 and 29, with a prolonged infusion of 5-fluorouracil (1,000 mg/m2) on Days 1–4 and 29–32, plus concurrent radiotherapy (50.4 Gy in 1.8-Gy fractions daily). For TOMOX-RT, raltitrexed (3 mg/m2) and oxaliplatin (130 mg/m2) was given on Days 1, 19, and 38 with the same radiotherapy regimen as used for PLAFUR. Surgery was performed 6–8 weeks after completion of chemoradiotherapy. All pathologic specimens were reviewed by a designated expert pathologist. The primary endpoint of this study was pathologic tumor downstaging (defined as tumor regression grade 1-2). Secondary endpoints included the incidence of ypT0, clinical tumor downstaging, sphincter-saving surgery, and acute treatment-related toxicity. Results: Between 2002 and 2005, 164 patients were accrued in 10 Italian centers, 83 patients in the PLAFUR arm and 81 in theTOMOX-RTarm. Overall, tumor regression grade 1-2 was observed in 76 patients (46.4%) and ypT0 in 49 (29.9%). The tumor regression grade 1-2 rate was 41.0% vs. 51.9% (p = 0.162) and the ypT0 rate was 24.1% vs. 35.8% (p = 0.102) for the PLAFUR vs. TOMOX-RT arm, respectively. The overall rate of tumor regression grade 1 and ypN+ was 4.6%. The occurrence of ypT downstaging was significantly greater in the TOMOX-RTarm (p = 0.035). Grade 3-4 acute toxicity occurred in 19 patients (11.6%): 7.1% in the PLAFUR arm vs. 16.4% in the TOMOX-RT arm. Sphincter-saving surgery was performed in 143 patients (87.2%) overall: 87.9% in the PLAFUR arm and 86.4% in the TOMOX-RT arm.
RANDOMIZED, MULTICENTER, PHASE IIB STUDY OF PREOPERATIVE CHEMORADIOTHERAPY IN T3 MID-DISTAL RECTAL CANCER: RALTITREXED + OXALIPLATIN + RADIOTHERAPY VERSUS CISPLATIN + 5-FLUOROURACIL + RADIOTHERAPY
GENOVESI, Domenico;
2008-01-01
Abstract
Purpose: To prospectively compare the rates of pathologic response, acute toxicity, and sphincter preservation with two different schedules of preoperative chemoradiotherapy in patients with cT3 mid-distal rectal cancer. Methods and Materials: Patients with cT3 and/or N+ resectable rectal carcinoma were randomized to receive one of the two following chemoradiotherapy regimens: cisplatin, 5-fluorouracil, and radiotherapy (PLAFUR) or raltitrexed, oxaliplatin, and radiotherapy (TOMOX-RT). For PLAFUR, cisplatin (60 mg/m2) was given on Days 1 and 29, with a prolonged infusion of 5-fluorouracil (1,000 mg/m2) on Days 1–4 and 29–32, plus concurrent radiotherapy (50.4 Gy in 1.8-Gy fractions daily). For TOMOX-RT, raltitrexed (3 mg/m2) and oxaliplatin (130 mg/m2) was given on Days 1, 19, and 38 with the same radiotherapy regimen as used for PLAFUR. Surgery was performed 6–8 weeks after completion of chemoradiotherapy. All pathologic specimens were reviewed by a designated expert pathologist. The primary endpoint of this study was pathologic tumor downstaging (defined as tumor regression grade 1-2). Secondary endpoints included the incidence of ypT0, clinical tumor downstaging, sphincter-saving surgery, and acute treatment-related toxicity. Results: Between 2002 and 2005, 164 patients were accrued in 10 Italian centers, 83 patients in the PLAFUR arm and 81 in theTOMOX-RTarm. Overall, tumor regression grade 1-2 was observed in 76 patients (46.4%) and ypT0 in 49 (29.9%). The tumor regression grade 1-2 rate was 41.0% vs. 51.9% (p = 0.162) and the ypT0 rate was 24.1% vs. 35.8% (p = 0.102) for the PLAFUR vs. TOMOX-RT arm, respectively. The overall rate of tumor regression grade 1 and ypN+ was 4.6%. The occurrence of ypT downstaging was significantly greater in the TOMOX-RTarm (p = 0.035). Grade 3-4 acute toxicity occurred in 19 patients (11.6%): 7.1% in the PLAFUR arm vs. 16.4% in the TOMOX-RT arm. Sphincter-saving surgery was performed in 143 patients (87.2%) overall: 87.9% in the PLAFUR arm and 86.4% in the TOMOX-RT arm.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
