Rectal Cancer: The STAR Study That Didn't Shine
Aschele C, Cionini L, Lonardi S, et al
J Clin Oncol. 2011;29:2773-2780
Fluorouracil-based preoperative chemoradiation is the current standard of care for locally advanced rectal cancer. In this large, randomized study of 747 patients, Aschele and coworkers evaluated the benefit of adding oxaliplatin (60 mg/m weekly x 6 weeks) to fluorouracil (225 mg/m/day) with standard-dose pelvic radiation (50.4 Gy in 28 fractions). The primary endpoint of the study was survival, and data are not mature yet to assess survival. In this report, the investigators described response rates and toxicity in both arms. Unexpectedly, the addition of oxaliplatin did not result in an increase in pathologic complete response rates (16% in both arms), node positivity (26% vs 29%), tumor infiltration beyond muscularis propria (46% vs 44%), or positive circumferential margins (7% vs 4%) (P nonsignificant for all). Oxaliplatin did enhance grade 3-4 adverse events (24% vs 8% for control arm). The only benefit to patients randomly assigned to oxaliplatin was a lower rate of intra-abdominal metastases that were unknown prior to resection (2.9% vs 0.5% with oxaliplatin, P = .01).
The data from multiple trials in patients with metastatic colorectal cancer have unequivocally established the superiority of oxaliplatin-based regimens over fluorouracil alone. Smaller phase 1 and phase 2 studies in rectal cancer have also suggested that the addition of oxaliplatin to preoperative regimens could enhance pathologic complete response rates. Once again, however, we find that a well-done and adequately powered randomized trial overturns what appear to be obvious assumptions. It is still possible, particularly given the positive impact of oxaliplatin on metastatic disease in this study, that survival outcomes could favor the use of oxaliplatin. For now, however, 5-fluorouracil alone with pelvic radiation remains the standard of care in the preoperative treatment of locally advanced rectal cancer.
Abstract
Primary Tumor Response to Preoperative Chemoradiation With or Without Oxaliplatin in Locally Advanced Rectal Cancer: Pathologic Results of the STAR-01 Randomized Phase III Trial
Aschele C, Cionini L, Lonardi S, et al
J Clin Oncol. 2011;29:2773-2780
Study Summary
Fluorouracil-based preoperative chemoradiation is the current standard of care for locally advanced rectal cancer. In this large, randomized study of 747 patients, Aschele and coworkers evaluated the benefit of adding oxaliplatin (60 mg/m weekly x 6 weeks) to fluorouracil (225 mg/m/day) with standard-dose pelvic radiation (50.4 Gy in 28 fractions). The primary endpoint of the study was survival, and data are not mature yet to assess survival. In this report, the investigators described response rates and toxicity in both arms. Unexpectedly, the addition of oxaliplatin did not result in an increase in pathologic complete response rates (16% in both arms), node positivity (26% vs 29%), tumor infiltration beyond muscularis propria (46% vs 44%), or positive circumferential margins (7% vs 4%) (P nonsignificant for all). Oxaliplatin did enhance grade 3-4 adverse events (24% vs 8% for control arm). The only benefit to patients randomly assigned to oxaliplatin was a lower rate of intra-abdominal metastases that were unknown prior to resection (2.9% vs 0.5% with oxaliplatin, P = .01).
Viewpoint
The data from multiple trials in patients with metastatic colorectal cancer have unequivocally established the superiority of oxaliplatin-based regimens over fluorouracil alone. Smaller phase 1 and phase 2 studies in rectal cancer have also suggested that the addition of oxaliplatin to preoperative regimens could enhance pathologic complete response rates. Once again, however, we find that a well-done and adequately powered randomized trial overturns what appear to be obvious assumptions. It is still possible, particularly given the positive impact of oxaliplatin on metastatic disease in this study, that survival outcomes could favor the use of oxaliplatin. For now, however, 5-fluorouracil alone with pelvic radiation remains the standard of care in the preoperative treatment of locally advanced rectal cancer.
Abstract