Background: Clinical trials investigating the effects of addition of oxaliplatin to neoadjuvant radiochemotherapy in locally advanced rectal cancers (LARC) have brought controversial results for pathologic complete response as an endpoint.
Aim: This phase III randomized study investigated downstaging as a short term surrogate for progression free survival (PFS).
Methods: Patients with MRI defined T3, T4 or N+ histologically proven adenocarcinoma of rectum within 15 cm from anal verge were randomly assigned to receive 50-50.4 Gy external beam radiation in 25-28 fractions and concurrent capecitabine 825 mg/m2 twice daily 5 days a week with or without oxaliplatin 60 mg/m2 weekly as neoadjuvant radiochemotherapy (capox and cap group respectively). T and N downstage were defined as at least one stage regression in pathologic report after surgery comparing to MRI image before the pre-operative treatment. Adverse effects of treatment were recorded on a weekly basis according to National Cancer Institute Common Toxicity Criteria, version 4.
Results: 63 patients were randomly assigned to cap (n=31) and capox (n=32) groups. There was no grade 4 toxicity. The only grade 3 toxicity which occurred more in capox group was diarrhea (21.87% vs 0%; p=0.006) . Histopathologic stage of 52 patients (27 patients in cap and 25 patients in capox groups) were compared to their preoperative stage defined by MRI. There was a greater rate of T downstage in capox group (59.37% vs 41.93%; p=0.037). The N downstage occurred non-significantly more in capox group (62.5% vs 51.6%; p=0.424). 11 patients in capox group (34.37%) achieved pathologic complete response, comparing to 4 in cap group (12.9%); p=0.072.
Conclusions: The addition of oxalipatin to neoadjuvant radiochemotherapy in LARC led to higher rate of tumor downstaging. Longer follow up is needed to evaluate PFS.