Rectal Cancer Complete Pathological Response Boosted with Extra Pre-Op Chemotherapy

Additional neoadjuvant chemotherapy improves the complete pathological response rate in locally advanced rectal cancer patients

medwireNews: Research shows that the likelihood of patients with locally advanced rectal cancer achieving a complete pathological response before surgery is increased by the use of mFOLFOX6 chemotherapy between neoadjuvant chemoradiation and total mesorectal excision.

The rate of complete pathological response increased from 18% for the 60 patients who underwent resection 6 to 8 weeks after fluorouracil plus radiotherapy to 25% for the 67 patients who also received two cycles of mFOLFOX6 before surgery.

And the rate rose to 30% for the 67 patients given four cycles of mFOLFOX6 and to 38% for the 65 patients given six cycles between chemoradiation and resection, the authors report in The Lancet Oncology.

Indeed, mFOLFOX6 receipt was independently associated with the likelihood of a complete pathological response, so that patients given six cycles were 3.49 times more likely to do so than those given no mFOLFOX6 after adjusting for radiation dose, clinical stage, and tumour size and distance from anal verge.

Julio Garcia-Aguilar, from Memorial Sloan Kettering Cancer Center in New York, USA, and co-workers explain that a pathological complete response to neoadjuvant chemoradiation has been established as a positive Prognostic marker for locally advanced rectal cancer and may also be an opportunity to reduce, avoid or delay the need for surgery.

“Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies”, they write, noting that a watch-and-wait surgery strategy for this population is now being tested in phase III clinical trials.

The researchers note that a partial or complete primary tumour response occurred in all patients who received additional chemotherapy after chemoradiation.

The rate of adverse events after mFOLFOX6 treatment increased with dose, so that 3% of patients given two cycles had grade 3 events, rising to 18% of those given four cycles and 28% of those given six cycles. Grade 4 events were reported in one patient given two cycles and five patients given six cycles.

Nevertheless, the number of cycles of mFOLFOX6 did not alter the technical difficulty of the surgery, the proportion of patients who had sphincter-saving surgery and negative surgical margins, the volume of blood loss, or the rate of grade 3 or higher adverse events and complications associated with the procedure.

“[W]e show that this approach seems to be safe from both an oncological and surgical standpoint; it did not increase the risk of tumour progression, technical difficulty, or surgical complications”, the authors conclude.

“If these findings can be reliably reproduced, a far greater number of patients with locally advanced rectal cancer will be eligible for organ preservation, which would improve functional outcomes and quality of life.”

Reference

Garcia-Aguilar J, Chow OS, Smith DS, et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol; Advance online publication 14 July 2015. DOI: dx.doi.org/10.1016/S1470-2045(15)00004-2

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2015