The STAR-01 trial similarly investigated the role of oxaliplatin combined with 5-FU chemoradiation for locally advanced rectal cancer. This Italian study randomly assigned 747 patients with resectable, locally advanced, clinically staged T3 or T4 and/or clinical N1 to N2 adenocarcinoma of the mid- to low-rectum to receive either continuous-infusion 5-FU with radiation or to receive the same regimen in combination with oxaliplatin (60 mg/m2). Although the primary endpoint was OS, a protocol-planned analysis of response to preoperative therapy has been preliminarily reported. The rate of pCR was equivalent at 16% in both arms (OR 0.98; 95% CI, 0.66–1.44, P = .904). Additionally, there was no difference noted in the rate of pathologically positive lymph nodes, tumor infiltration beyond the muscularis propria, or the rate of circumferential margin positivity. Again, an increase in grades 3 to 4 treatment-related acute toxicity was noted with the addition of oxaliplatin (24% vs. 8%, P <.001). Longer-term outcomes including OS have not yet been reported.[Level of evidence: 1iiA]
The NSABP-R-04 trial randomly assigned 1,608 patients with clinically staged T3 or T4 or clinical node-positive adenocarcinoma within 12 cm of the anal verge in a 2 × 2 factorial design to one of the following four treatment groups:
- Intravenous continuous infusion (IVCI) 5-FU with radiation therapy.
- Capecitabine with radiation therapy.
- IVCI 5-FU plus weekly oxaliplatin with radiation therapy.
- Capecitabine plus weekly oxaliplatin with radiation therapy.
The primary objective of this study is locoregional disease control.
Preliminary results, reported in abstract form at the 2011 American Society of Clinical Oncology annual meeting, demonstrated that there was no significant difference in the rates of pCR, sphincter-sparing surgery, or surgical downstaging between the 5-FU and capecitabine regimens or between the regimens with and without oxaliplatin. However, similar to the other studies, patients treated with oxaliplatin had significantly higher rates of grade 3 and 4 acute toxicity (15.4% vs. 6.6%, P < .001).[Level of evidence: 1iiD]
The German CAO/ARO/AIO-04 trial randomly assigned 1,236 patients with clinically staged T3 to T4 or clinical node-positive adenocarcinoma within 12 cm from the anal verge to receive either concurrent chemoradiation with 5-FU (week 1 and week 5) or concurrent chemoradiation with 5-FU daily (250 mg/m2) and oxaliplatin (50 mg/m2). In contrast to the previous studies, a significantly higher rate of pCR was achieved in patients who received oxaliplatin (17% vs. 13%, P = .038). There was no significant difference in rates of overall grades 3 and 4 toxicity, however, diarrhea and nausea and vomiting were more common among those treated with oxaliplatin. The 5-FU schedules in this study differed between the two arms, which may have contributed to the difference in outcomes noted. Longer follow-up will be necessary to determine the effect on the primary endpoint of the study, DFS.[Level of evidence: 1iiD]