Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results.

PURPOSE: Organ-sparing therapy for early-stage I/IIA rectal cancer is intended to avoid functional disturbances or a permanent ostomy associated with total mesorectal excision (TME). The objective of this phase II trial was to determine the outcomes and organ-sparing rate of patients with early-stage rectal cancer treated with neoadjuvant chemotherapy followed by transanal excision surgery (TES). METHODS: This phase II trial included patients with clinical T1-T3abN0 low- or mid-rectal adenocarcinoma eligible for endoscopic resection who were treated with 3 months of chemotherapy (modified folinic acid-fluorouracil-oxaliplatin 6 or capecitabine-oxaliplatin). Those with evidence of response proceeded to transanal endoscopic surgery 2-6 weeks later. The primary end point was protocol-specified organ preservation rate, defined as the proportion of patients with tumor downstaging to ypT0/T1N0/X and who avoided radical surgery. RESULTS: Of 58 patients enrolled, all commenced chemotherapy and 56 proceeded to surgery. A total of 33/58 patients had tumor downstaging to ypT0/1N0/X on the surgery specimen, resulting in an intention-to-treat protocol-specified organ preservation rate of 57% (90% CI, 45 to 68). Of 23 remaining patients recommended for TME surgery on the basis of protocol requirements, 13 declined and elected to proceed directly to observation resulting in 79% (90% CI, 69 to 88) achieving organ preservation. The remaining 10/23 patients proceeded to recommended TME of whom seven had no histopathologic residual disease. The 1-year and 2-year locoregional relapse-free survival was, respectively, 98% (95% CI, 86 to 100) and 90% (95% CI, 58 to 98), and there were no distant recurrences or deaths. Minimal change in quality of life and rectal function scores was observed. CONCLUSION: Three months of induction chemotherapy may successfully downstage a significant proportion of patients with early-stage rectal cancer, allowing well-tolerated organ-preserving surgery.

Adjuvant chemotherapy for stage III colon cancer: does timing matter?

BACKGROUND: Clinical trials commonly mandate that adjuvant chemotherapy for colon cancer should commence within 8 weeks (56 days) of surgery. OBJECTIVE: We investigated the consequences of the timing of adjuvant chemotherapy for stage III colon cancer. PATIENTS AND METHODS: This is a retrospective review of all patients with newly diagnosed stage III colon cancer who received adjuvant chemotherapy in 2 provincial centers in 1999 and 2000. The impact of time to adjuvant chemotherapy on overall survival and relapse-free survival was analyzed by the use of univariate and multivariate Cox modeling, adjusting for prognostic factors. RESULTS: Three hundred forty-five subjects were included. Median time to adjuvant chemotherapy was 50 days (range, 20-242 days); in 111 (32.2%) patients, it was beyond 56 days. On univariate analysis, time >56 days was nonsignificantly associated with a hazard ratio of death of 1.31 (P = .12). Similar results were seen for relapse-free survival. Planned exploratory analysis suggests that the commencement of adjuvant chemotherapy up to 10 weeks postsurgery still confers a benefit. CONCLUSIONS: Delaying adjuvant chemotherapy in stage III colon cancer beyond 8 to 10 weeks postsurgery appears to be associated with diminished benefit.