Neoadjuvant Chemotherapy in Colon Cancer Is Safe and Feasible

Standard treatment for stage III colon cancer consists of surgery followed by 3 months of a fluorinated pyrimidine plus oxaliplatin, with the option to extend the fluorinated pyrimidine to 6 months in patients with high-risk disease. For stage II cancer, adjuvant treatment is controversial, and current options include no such therapy, 6 months of fluorinated pyrimidine, or 3 months of fluorinated pyrimidine with oxaliplatin. Recent trials evaluating the effectiveness of administering some chemotherapy preoperatively versus all of it postoperatively have yielded mixed results.

In the latest such trial (OPTICAL), investigators in China randomized patients to 3 months of preoperative chemotherapy (with either mFOLFOX6 [fluorouracil, leucovorin, oxaliplatin] or CAPOX [capecitabine and oxaliplatin]) followed by 3 months of postoperative chemotherapy or to 6 months of chemotherapy all administered postoperatively. Of the 744 evaluable patients, 25% had clinical stage T3 cancer on CT scan, 75% had stage T4, 77% had node-positive status, and 56% had left-sided primary cancers. In the preoperative group, 70% received mFOLFOX6, and 30% received CAPOX; overall, 58% completed preoperative therapy. Adjuvant therapy was started after surgery in 83% of the preoperative group and 80% of the postoperative-only group.

At a median follow-up of 48 months, 3-year disease-free survival, the primary endpoint, was not significantly improved in the preoperative group compared with the postoperative-only group (82.1% vs. 77.5%; hazard ratio, 0.74; P=0.07). However, subgroup analyses suggested a more pronounced benefit of preoperative therapy among female patients (86.5% vs. 75.3%; HR, 0.54). Among all patients, the preoperative group had significantly better 3-year overall survival than the postoperative-only group (95.1% vs. 89.6%; HR 0.44; P=0.01) and modest pathologic downstaging, with 7% of patients achieving a pathologic complete response. Rates of grade 3/4 serious adverse events were similar in both groups.