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The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04.
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2011
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Surgical OncologyPreoperative Multimodality TreatmentOral CapecitabineNsabp R-04Cancer ManagementMultimodalitySurgeryTreatment VerificationRadiation MedicineOncologyGastrointestinal OncologyPreop RtClinical Radiation OncologyRadiation OncologyCancer ResearchMolecular OncologyRadiation TherapyPreop Radiation TherapyCancer TreatmentMedicine
3503 Background: The optimal chemotherapy regimen to be given concurrently with preop radiation therapy (RT) in patients with resectable adenocarcinoma of the rectum is unknown. NSABP R-04 compared the efficacy of 4 chemotherapy regimens administered concomitantly with preop RT. Methods: Patients with clinical stage II or III rectal cancer undergoing preop RT (4,500cGy in 25 fractions over 5 wk + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous IV infusion (CVI) 5-FU (225mg/m2 5 days/wk), with or without IV oxaliplatin (OX) (50mg/m2 /wk x 5); oral capecitabine (CAPE) (825 mg/m2 BID 5 days/wk), with or without OX (50mg/m2/wk x 5). Prior to random assignment the surgeon indicated if the patient was eligible for sphincter-saving surgery (SSS) based on clinical staging. The endpoints were complete pathologic response (pCR), SSS, and surgical downstaging (SD, conversion to SSS). Results: From July 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, SSS, or SD were identified between the 5-FU and CAPE regimens or between the regimens, with and without OX (Table). Patients treated with OX experienced significantly more grade 3/4 diarrhea. Conclusions: Administration of capecitabine with preop RT achieved similar rates of pCR, SSS, and SD compared to CVI 5-FU. The addition of oxaliplatin did not improve preliminary outcomes but added significant toxicity. The definitive analysis of local tumor control will be performed in fall 2013. Funded by NCI PHS grants U10-CA-37377, U10-CA-69974, U10-CA-12027, U10-CA-69651, and U10-CA-25224 with support from sanofi-aventis US Inc. and Hoffmann La-Roche. Endpoint 5-FU (± OX) CAPE (± OX) P value pCR 135/719 = 18.8% 157/707 = 22.2% 0.12 SSS 445/727 = 61.2% 445/710 = 62.7% 0.59 SD 39/188 = 20.7% 43/187 = 23.0% 0.62 Grade 3/4 diarrhea 70/625 = 11.2% 68/628 = 10.8% 0.86 Endpoint (FU or CAPE) No OX (FU or CAPE) + OX P value pCR 111/580 = 19.1% 121/578 = 20.9% 0.46 SSS 370/582 = 63.6% 353/584 = 60.4% 0.28 SD 35/152 = 23.0% 29/151 = 19.2% 0.48 Grade 3/4 diarrhea 41/622 = 6.6% 97/631 = 15.4% < 0.0001