Administering the triple approach of oxaliplatin (OXA) , raltitrexed (RTX) and 5 fluorouracil (5-FU)/ levo-folinic acid (LFA) to rectal cancer patients (RC) undergoing preoperative pelvic radiotherapy delivered promising results, finds an Italian study published in the International Journal of Radiation Oncology.

Despite improvements in the treatment of locally advanced RC, management of the disease remains challenging. While the combination of total mesorectal excision, preoperative radiotherapy and 5-FU has resulted in reductions of local recurrence, there has been little impact on distant metastases or survival underlining the need for new approaches. For many years, 5-FU has been the only drug associated with local radiotherapy, due to its radiosensitizing and cytotoxic effects. In the current study Antonio Avallone and colleagues, from the National Cancer Institute (Naples, Italy), set out to assess the safety and efficacy of combining 5-FU with OXA and RTX.

In the study 63 patients with a poor prognosis for RC received three biweekly courses of chemotherapy with OXA and RTX on day 1, and 5-FU or LFA on day 2. Surgery was planned to take place eight weeks after the completion of CRT. Pathologic responses were defined as complete, major, minor or no response.

Results show that overall a complete pathological response was obtained in 39% (24) patients, and a major response was obtained in 32% (20) patients. Furthermore, the overall 5-year probability of freedom from recurrence was 80% (95% CI 68 % -92%); it was 56% for the minor/no response group; while it was around 90% for both the complete pathological response group and the major response group. The most common >grade 3 toxicities were neutropenia (40%) and diarrhoea (13%), with tolerability found to be better for patients who had a 5-FU dose reduction.

"The improved tolerability translated to better compliance with the planned CT treatment," write the authors.

The combination of OXA, RTX, and 5-FU/LFA, concluded the authors, produces promising early and long term results in poor prognosis patients with locally advanced rectal cancer. The results, they add, need confirmation in a larger study population.

Article: A Avallone, P Delrio, B Pecori et al. Oxiplatin plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy for locally advanced rectal carcinoma: long term outcome. Int J, Radiation Oncology. Biology, Physics. 2011, 79, pp670-679.