Short-course radiation therapy, neoadjuvant bevacizumab, capecitabine and oxaliplatin, and radical resection of primary tumor and metastases in primary stage IV rectal cancer: A phase II multicenter study of the Dutch Colorectal Cancer Group.

Abstract

3638 Background: There is no standard treatment regimen in stage IV rectal cancer. We conducted a phase II study to test the efficacy of 5x5 Gy to the pelvic followed by 6 cycli chemotherapy and resection of both primary tumor and metastasis. Methods: Pts with primary rectal cancer and synchronous resectable metastases in 1 or 2 organs, ECOG PS 0-1, limited comorbidity and signed informed consent were eligible. Treatment was started with 5 fractions of 5 Gy radiation therapy to the pelvis. After 1 week bevacizumab (7.5 mg/kg.), capecitabine (2dd 1,000 mg/m2) and oxaliplatin (130 mg/m2) were administered in cycles of 3 weeks. Restaging was performed after 2 cycles. Unless progression was demonstrated, chemotherapy was continued with another 4 cycles. Primary endpoint was radical resection and/or (RF) ablation of the primary tumor and all metastastic lesions. Secondary endpoints are two-year survival and two-year recurrence rate. Results: From January 2006 50 pts (27 male) were enrolled in 7 Dutch centres; median age was 58.5 years (35-75). 42 pts had metastasis in the liver, 5 in the lung en and 3 in both lung and liver. No toxicity was seen in 5x5 Gy RT. Median time from RT to CT was 11 days (3-44). Grade 3-4 toxicities during chemotherapy: diarrhea (5), thrombosis (5), fatigue (2), pain (2), handfoot-syndrome (1), cholecystitis (1) and constipation (1). No progression was seen during chemotherapy. Radical surgical treatment was achieved in 33 of the 41 pts that have been operated. In 27 patients surgery of rectum and liver was done simultaneously. No treatment related deaths occurred. Complete response (CR) or near-CR (TRG 1-2) of the rectal tumor was seen in 44%. Median time to recurrence after R0 resection was 12 months (7-34). 21 of the 33 pts presented with a recurrence after R0 resection. With a median follow-up of 24 months in the R0 group 7 patients (21%) died. Conclusions: Short course pelvic radiotherapy followed by systemic chemotherapy is a well tolerated neoadjuvant approach in primary stage IV rectal cance with a R0 resection rate of the rectal tumor in 44%. No significant financial relationships to disclose.