3528 Background: The addition of chemotherapy to preoperative radiotherapy (RT) may reduce distant recurrence and increase tumor resectability. The CORE study evaluated oxaliplatin, capecitabine, and RT (XELOX-RT) followed by total mesorectal excision (TME), then adjuvant XELOX in patients (pts) with MRI-defined locally advanced rectal cancer. Methods: MRI inclusion criteria: tumor beyond mesorectal fascia, tumor ≤2 mm from mesorectal fascia, or T3/4 tumor <5 cm from anal verge. Chemoradiation (CRT) was 45 Gy RT (1.8 Gy/dose) 5 days/wk for 5 wks, weekly oxaliplatin 50 mg/m2, and twice-daily capecitabine 825 mg/m2 on each day of RT. Surgery was 6–8 wks after completing XELOX-RT. Pts with R0-R1 resection were to receive XELOX for 6 cycles. Central radiologic and histopathologic review were key study components. Processes to determine histopathologic response and circumferential resection margin (CRM) were predefined. The primary endpoint was pCR rate (planned n=70 evaluable pts). Results: Between July 2003 and Dec 2004, 87 pts were enrolled; 85 pts received XELOX-RT and 79 had TME. Seventy pts (82%) had R0-R1 resection, with a 67% R0 rate (n=57) by Quirke methodology (CRM >1 mm). The pCR rate was 13% (10/78 pts assessable for tumor response; 95% CI, 5.46–20.34%). Tumor regression grading showed excellent response in 35% and poor response in 64% of pts. Of 60 pts evaluated by central MRI review for response by RECIST, the overall response rate was 70% (7% complete; 63% partial response). Preoperative grade (G) 3/4 adverse events (% of pts; evaluable n=85) included diarrhea 16% (12% G3), sensory neuropathy 1% (G3), neutropenia 1% (G3), and hand-foot syndrome 1% (G3). More than 90% of pts received full dose radiotherapy. Conclusions: Significant tumor regression and a high R0 resection rate were achieved using a CRT regimen of preoperative oxaliplatin, capecitabine, and 45 Gy RT, with acceptable toxicity. Central histopathologic and radiologic review data, together with safety and efficacy results for both preoperative CRT and postoperative chemotherapy, will be presented. [Table: see text]
524 Background: The SOR-CAP combination has shown clinical activity in several phase I-II trials involving metastatic breast cancer and mCRC patients (pts). SoMore aims to substantiate the combination’s effects in mCRC refractory to all medications and the predictive value of early metabolic response (MR) on survival. Methods: SoMore (EUDRACT 2010-023695-91) has 2 coprimary objectives: 1) to demonstrate an overall survival (OS) rate at 6 months (mths) > 30%, and 2) to compare OS between pts with and without MR. CAP was given at 1700 mg/m²/day (D), 2 weeks out of 3. SOR was administered at 600mg/D for the first cycle, then at 800mg/D until progression or unacceptable toxicity. FDGPET-CT was performed at baseline and before the 2nd cycle. MR analysis was centralized and blinded for the investigators. Results: From February to October 2011, 92 eligible pts were prospectively recruited in 6 Belgian centers: M/F: 54%/46%; ECOG PS 0/1: 55%/45%; median age: 61. A median of 5 treatment cycles were given (0-28+). Grade 3-4 toxic reactions were reported in 61.2%, mainly fatigue (18%), hand-foot skin reaction (14%) and diarrhea (11%), but no toxic death. 6.9% of the pts stopped therapy due to toxicity. 6 mths OS was 71% (95% CI: 61%-79%), significantly >30% (p<0.001). 47% of the 79 pts evaluable for metabolic assessment showed homogeneous MR (HMR) of all metastatic lesions, 32% mixed MR and 21% homogeneous non-MR. Median overall OS and PFS of the intent-to-treat population and of pts with and without HMR are shown in the table below. Hazard ratio for HMR was 0.34 (95% CI, 0.21 to 0.56) p-value <0.001 for PFS and 0.59 (95% CI, 0.37 to 0.96) p-value 0.03 for OS. Conclusions: These data suggest robust efficacy for the SOR-CAP combination in heavily pretreated mCRC, associated with high but manageable toxicity. Early MR assessment, by detecting unresponsive lesions within the whole body tumoral load, is able to capture the pts’ likelihood of benefit, opening the path to personalized medicine. Clinical trial information: NCT01290926. [Table: see text]
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