Cetuximab, capecitabine, and oxaliplatin (Cet-CapOx) with concurrent radiotherapy (RT) in advanced rectal cancer (RC): Results of a phase I/II trial

Abstract

4042 Background: CapOx given concurrently with neoadjuvant RT in rectal cancer is well tolerated and has achieved high rates of pathologic complete response (pCR) in phase II trials. Cetuximab is active in metastatic colorectal cancer. Synergy of cetuximab with RT resulted in improved survival (vs. RT alone) in head and neck cancer. This trial was to evaluate feasibility and efficacy of Cet-CapOx in RT of rectal cancer, with maximal tolerated dose as primary endpoint in phase I, and pCR as primary endpoint in phase II. Method: Patients (pts) had to have untreated, T3–4 and/or N+ disease per MRI or CT plus endoscopic ultrasound, M1 allowed, normal organ function. During conventionally fractionated RT (1.8 Gy for 28 days [d]), cetuximab was given in standard dose (400 mg/m2 on d - 7, then 6 weekly doses of 250 mg/m2, to d35). CapOx was administered as in the phase II trial of our group (Rödel et al, J Clin Oncol 2007), with oxaliplatin (50 mg/m2 d 1,8,22 and 29) plus capecitabine (d1–14 and d22–35) at 3 dose levels: 1,000, 1,300 and 1,650 mg/m2/day. Results: 60 pts were enrolled: Median age 62 [35–83] yrs., male 61%, T3/T4 83/17%, N+ 85%, M1 20%. 7/ 3/ 50 pts. were treated on levels 1/ 2/ 3: as only 1 pt. experienced DLT (diarrhea 4°) on level 1 and none on level 2, level 3 was chosen for phase II (n=50 pts.). Most common toxicity was CTC grade 3 diarrhea in 14% of pts. Full dose of all drugs and of RT was administered in >90% of cycles. No grade 4 toxicity occurred. 53/60 pts underwent resection after completed chemoradiation without increase of perioperative complications when compared to historic controls of CapOx-RT alone. Radiologic downstaging (17 pts. evaluated so far) was seen in 35% for T category and in 67% for N category. Pathologic complete response (45 pts. evaluable) was observed in 9% of pts, another 38% had “good regression” (>50% of tumor cells). Conclusion: CapOx can safely be combined with cetuximab without requiring dose reduction of chemo- or radiotherapy and leads to significant downstaging. However, the relatively low rate of pathologic responses underachieved the assumptions. [Table: see text]