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Oxaliplatin pre-, post-surgery extends DFS for patients with advanced rectal cancer

Thursday, August 13, 2015

The addition of oxaliplatin to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy significantly improved DFS among patients with locally advanced rectal cancer, according to results of a phase 3 trial. Heather Yeo, M.D., provided commentary in the work for Healio.com. Read the full text here.

Photo of Dr. Heather YeoDr. Heather Yeo Rödel and colleagues have performed a well-designed multicenter open label randomized phase 3 study of locally advanced rectal cancer. However, caution needs to be exercised when using these results to counsel patients as the demonstrated absolute gain in DFS was low. Toxicity also needs to be considered, especially in light of the fact that the roles of neoadjuvant and adjuvant chemotherapy and chemoradiotherapy are still in evolution. 
 
At 3 years, Rödel and colleagues report an absolute gain in DFS of 4.7% and the absolute reduction in distant recurrences of 3.9%. This absolute benefit of oxaliplatin is real, but should be balanced against the extra toxicity. Although differences may appear less striking than what has been shown in other trials because of the 5-FU schedule selected, still, 22% of those receiving oxaliplatin had a grade 2 neuropathy compared with 1% of those in the 5-FU group, and 11% had a grade 3 to grade 4 neuropathy compared with less than 1% respectively of those in the 5-FU group.
 
In addition, only 190 (44%) of patients in the oxaliplatin group were able to complete their fully allotted chemotherapy at the doses scheduled compared with 301 (65%) of patients in the FU group alone. There was no statistically significant difference in OS between the two groups, and there was a slight increase in treatment-related cause of death in the investigational group, even though slightly more patients died in the control group. As mentioned, the regimen chosen for the control group was more toxic than that seen in the PETACC-2 trial and other trials, making the toxicity from the control group higher than it might otherwise be. 
 
Current management of rectal cancer is still under debate. There are several questions that still cannot be answered because of the way this study was designed. The benefit of oxaliplatin as a chemoradiosensitizer is still unclear. Several other trials have examined oxaliplatin alongside with 5-FU and radiation, and all others have failed to show a benefit. The neoadjuvant and adjuvant nature of this study make it difficult to know where oxaliplatin is having its effect. However, because the complete response rate was the same in both arms, it is possible that the benefit is more as adjuvant therapy than as a radiosensitizer.
 
As the researchers point out, due to current surgical technique and treatment options, local regional control is well obtained. The more life-threatening issue for patients is distant spread, an issue several groups are now addressing, in particular with regard to the use of neoadjuvant FOLFOX as opposed to or in addition to neoadjuvant chemoradiotherapy, the need for radiation therapy in the treatment protocol, and ways to identify pathologic complete responders. The trial by Rödel and colleagues was well done, but there are still many questions in the management of rectal cancer.