Randomized, Multicenter, Phase IIB Study of Preoperative Chemoradiotherapy in T3 Mid-Distal Rectal Cancer: Raltitrexed + Oxaliplatin + Radiotherapy Versus Cisplatin + 5-Fluorouracil + Radiotherapy
- Department of Radiation Therapy, Universita Cattolica Sacro Cuore, Rome (Italy)
- Department of Surgery, Universita Cattolica Sacro Cuore, Rome (Italy)
- Department of Radiation and Cellular Oncology, University of Chicago Hospitals, Chicago, IL (United States)
- Department of Radiation Therapy, Istituto Regina Elena, Rome (Italy)
- Department of Radiation Therapy, Universita degli Studi, Perugia (Italy)
- Department of Radiation Therapy, Centro Alta Tecnologia, Campobasso (Italy)
- Epidemiology and Biostatistics Unit, Institute of Hygiene, Universita Cattolica Sacro Cuore, Rome (Italy)
- Department of Radiation Therapy, Campus Biomedico, Rome (Italy)
- Department of Radiation Therapy, Universita Gabriele D'Annunzio, Chieti (Italy)
- Department of Radiation Therapy, Ospedale Civile, Brindisi (Italy)
- Department of Radiation Therapy, Universita La Sapienza, Rome (Italy)
- Department of Radiation Therapy, Universita degli Studi, Brescia (Italy)
- Department of Radiation Therapy, Ospedale Civile, Terni (Italy)
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/m{sup 2}) was given on Days 1 and 29, with a prolonged infusion of 5-fluorouracil (1,000 mg/m{sup 2}) 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/m{sup 2}) and oxaliplatin (130 mg/m{sup 2}) 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 the TOMOX-RT arm. 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-RT arm (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. Conclusions: Compared with the PLAFUR regimen, TOMOX-RT achieved a greater incidence of downstaging but was associated with a correspondingly greater rate of acute Grade 3+ toxicity. With longer follow-up, the local control and survival rates might offer additional guidance as to the choice of regimen.
- OSTI ID:
- 21039747
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 70, Issue 2; Other Information: DOI: 10.1016/j.ijrobp.2007.06.025; PII: S0360-3016(07)01145-5; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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