Oxaliplatin Addition May Benefit Locally Advanced Rectal Cancer Patients

Oxaliplatin may increase disease-free survival for locally advanced rectal cancer patients

medwireNews: Patients with locally advanced rectal cancer have significantly longer disease-free survival if oxaliplatin is added to their preoperative chemoradiotherapy and postoperative chemotherapy regimen, phase III results show.

After a median of 50 months, 3-year disease-free survival was achieved by 75.9% of 613 patients randomly assigned to receive open-label infusional fluorouracil and 50.4 Gy radiation plus oxaliplatin followed by postoperative infusional fluorouracil with leucovorin and oxaliplatin.

This compared with a 3-year disease-free survival rate of 71.2% of 623 patients given the established regimen of infusional fluorouracil and 50.4 Gy radiation followed by postoperative bolus fluorouracil, giving a significant hazard ratio of 0.79.

Three-year overall survival was comparable in the oxaliplatin and standard chemotherapy groups, at 88.7% and 88.0%, respectively.

In all, 95% of both treatment groups who underwent surgery achieved a complete locoregional resection and a pathological complete response was achieved by 17% versus 13% of patients given the oxaliplatin regimen and standard chemotherapy, respectively, with an odds ratio of 1.41. Distant metastases were found at surgery in 3% and 6%, respectively.

After 3 years, local recurrences after R0/1 surgery were reported for 2.9% and 4.6% of patients in the oxaliplatin and standard chemotherapy groups, respectively, while distant recurrences occurred in 18.5% and 22.4%, respectively.

Preoperative grade 3 or 4 side effects were reported by 24% of patients given fluorouracil plus oxaliplatin and 20% of patients who received only fluorouracil, and 36% of patients in both groups following postoperative treatment. Among the 445 oxaliplatin-treated patients who received per-protocol pre-and postoperative regimen, late grade 3 or 4 events were reported in 25%, versus 21% of those given the standard regimen.

“The multimodal treatment of this disease might be further refined by giving combination chemotherapy as an induction therapy before preoperative chemoradiotherapy and surgery rather than as an adjuvant treatment”, Claus Roedel, from the University of Frankfurt in Germany, and co-authors write in The Lancet Oncology.

“This concept of total neoadjuvant treatment is currently being addressed in our CAO/ARO/AIO-12 randomised phase 2 study.”

Bengt Glimelius, from Uppsala University in Sweden, notes in an accompanying comment that the trial’s inclusion criteria of “locally advanced” cancer to mean cT3 to T4 clinical staging or any node-positive disease patients was “suboptimal” as European guidelines designate this description for only cT3mrf+ and cT4 tumours.

“Adding oxaliplatin preoperatively and postoperatively to the treatment schedule of patients with a primary rectal cancer considered to be locally advanced as defined in the trial (cT3–4, any N+) could result in a pronounced overtreatment, risking long-lasting neuropathy in many patients”, Bengt Glimelius cautions.

“Updated results from additional trials will add to the knowledge base and make estimations of the potential gains clearer.”


Rödel C, Graeven U, Fietkau R, et al. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2015; Advance online publication 15 July. DOI: dx.doi.org/10.1016/S1470-2045(15)00159-X

Glimelius B. Is the benefit of oxaliplatin in rectal cancer clinically relevant? Lancet Oncol 2015; Advance online publication 15 July. DOI: dx.doi.org/10.1016/S1470-2045(15)00018-2

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