Pre-operative Radio-Chemotherapy of Rectal Cancer: Toxicity and Preliminary Results with the Addition of Weekly Oxaliplatin

The standard pre-operative treatment of rectal cancer consists of radiotherapy combined with continuous infusion Of fluorouracil (FU) at a dose of 200 mg/m(2)/day. Platinum compounds can increase the anti-tumour activity of radiotherapy and are suitable agents to be combined with FU. We report our experience with the addition of oxaliplatin to radiotherapy and FU in the pre-operative treatment of patients with rectal cancer. Patients with locally advanced rectal cancer (cT3-T4 and/or N+) were treated with pre-operative 5-FU (200 mg/m(2)/day, continuous infusion) and external beam radiation (45 Gy given to large fields plus a booster dose of 5.4 Gy, making a total of 50A Gy delivered in 28 daily fractions of 1.8Gy). Oxaliplatin was given at a dose of 50 mg/m(2) in 2 h once weekly. Inclusion and exclusion criteria for patients were standard and written informed consent was obtained before treatment. Surgery was planned 5 weeks after radiotherapy. Toxicity was graded using the NCI-CTC version 3. Oxaliplatin was suspended in cases of G3 haematological toxicity or G2 neurotoxicity; both oxaliplatin and FU were Suspended for G3 non-haematological toxicity. From November 2006 to January 2008, 21 patients were treated. All completed radiation treatment, and 16 received full dose chemotherapy. Chemotherapy was suspended due to G3 diarrhoea in 3 patients. We observed G2-3 proctitis in 11 patients (particularly painful in three), G1 allergic reactions in 3 of them and G1 neurotoxicity in 12. Fifteen patients were operated on. Of these, eight had a complete pathological response. The histological examination was negative in 3 patients despite the persistence of a palpable mass. Oxaliplatin can be added to standard chemoradiation in the pre-operative treatment of rectal cancer. Toxicity is increased and requires careful monitoring. The present report and literature data indicate that the anti-tumour efficacy is promising and we look forward to the results of large randomised trials currently in progress.