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Short-course chemoradiation regimen effective, less toxic for advanced rectal cancer
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A short-course 5-day radiation regimen followed by consolidated chemotherapy prior to surgery appeared as effective as and less toxic than the standard 5-week chemoradiation course for patients with advanced rectal cancer, according to phase 3 study results presented at the Gastrointestinal Cancers Symposium.
However, the short-course regimen failed to demonstrate a superior radical resection rate compared with standard chemoradiation.
“There is a great need for improvement of preoperative strategies for patients with locally advanced rectal cancer,” study researcher Lucjan Wyrwicz, MD, PhD, head of the medical oncology unit in the department of gastrointestinal cancer at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw, Poland, said in a press release. “The new regimen has similar efficacy but causes fewer side effects and is more convenient for patients. It is also less costly compared to standard chemoradiation, so it may be especially valuable in limited-resource settings.”
Chemoradiation — a standard of care in the U.S. to shrink the tumor and reduce the risk for recurrence prior to surgery — consists of 5 weeks of radiation with concurrent chemotherapy in weeks 1 and 5.
Wyrwicz and colleagues sought to evaluate an experimental regimen that includes 5 days of radiation and 6 days of chemotherapy delivered over 7 weeks.
The study included data from 515 patients with stage III or stage IV rectal cancer. Researchers randomly assigned patients to the control group (n = 254) — which consisted of a standard regimen of 50.4 Gy radiation delivered in 28 fractions given simultaneously with 5-FU, leucovorin and oxaliplatin — or the experimental group (n = 261), which received 5x5 Gy of radiation and three courses of FOLFOX4 chemotherapy after 1 week of rest. The researchers noted the addition of oxaliplatin to 5-FU in the control group is not standard practice in the U.S. due to an increase in toxicity.
Both cohorts underwent surgery approximately 12 weeks after radiation initiation and about 6 weeks following neoadjuvant treatment.
The rate of curative resection served as the study’s primary endpoint. Median follow-up was 35 months.
Overall, fewer patients in the experiment group experienced acute toxicity than patients in the control group (75% vs. 83%; P = .006). The rate of grade 3 or worse toxicity was 24% in both groups.
The most common toxicities associated with radiotherapy included diarrhea, inflammation of the bladder and/or rectum, and local skin radiation response.
The rate of curative resection was 77% in the experimental group vs. 71% in the control group, and the rate of pathological complete response was 16% in the experimental arm and 11.5% in the control arm.
“Despite the fact the trial was negative — superiority in radical resection rate has not been shown — short-course radiotherapy combined with three cycles of chemotherapy can be recognized as a new standard of treatment of advanced rectal cancer with threatened resection margin,” Wyrwicz said during a press briefing.
Seventy-three percent of patients in the experimental arm achieved 3-year OS compared with 65% of the control arm (P = .046).
“If this survival benefit is confirmed with longer follow-up, it might ultimately result in change to the clinical practice,” Wyrwicz said in the release.
A comparable proportion of patients in the experimental and control arms achieved 3-year DFS (53% vs. 52%) and experienced local failure (22% vs. 21%).
The researchers hypothesized that this shorter course of radiotherapy may be especially beneficial to patients with rectal cancer that has metastasized to the liver or lungs who are candidates for disease resection at all sites. This would allow patients to start chemotherapy to control those metastases sooner.
“This method is implemented in the treatment strategy of our patients,” Wyrwicz said in the release. “[It] seems to be feasible and effective in this rare subgroup of patients.” – by Anthony SanFilippo
Reference:
Bujko K, et al. Abstract 489. Presented at: Gastrointestinal Cancers Symposium; Jan. 21-23, 2016; San Francisco.
Disclosure: The researchers reported no relevant financial disclosures.
Perspective
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Daniel T. Chang, MD
The findings of this study are actually quite interesting. This is a trial that has been a long time coming — there has been a lot of interest comparing short-course radiation with conventional standard long-course chemoradiation.Previously, the Polish Colorectal Study Group had published one trial that showed no difference in most meaningful outcomes. This is a follow-up study that added consolidation chemotherapy following the short-course radiation, which is an interesting strategy.
In line with the previous trial, researchers found that there was worse toxicity with the long-course chemoradiation. However, they also observed no difference in local control or DFS.
What is most interesting is that this study actually demonstrated superior OS with short-course radiotherapy followed by three cycles of chemotherapy. This potentially indicates the benefit of adding early chemotherapy to address systemic disease.
What is also noteworthy about this trial is the fact that surgery actually occurred around the same time — week 12 — for both arms. That is important because the pathologic complete response rate in both arms was not statistically significantly different — 12% vs. 16% — although, it was higher in the short-course arm with chemotherapy.
These results could change the standard of care because there has been a lot of interest in moving away from long-course radiation. In a short course, if 1 week of radiotherapy followed by consolidation chemotherapy can be equally effective, this could perhaps alter the standard of care across the world.
Reference:
Bujko K, et al. Radiother Oncol. 2013;doi:10.1016/j.radonc.2013.03.001.Perspective
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Smitha Krishnamurthi, MD
This study demonstrates that short-course radiation followed by chemotherapy can achieve reduction in tumor as seen in a pathologic complete response of 16%, which is equal to that of chemoradiation. The short course has less acute toxicity than the chemoradiation.
However, we must keep in mind that the chemoradiation included oxaliplatin, which has been shown to increase toxicity of the regimen and is no longer a part of standard chemoradiation. Two previous comparisons of short-course vs. long-course radiation for rectal cancer found no significant difference in later toxicities; however, one study found a small increase in local recurrence in short-course radiation, particularly for distal rectal cancers.
In the present study, the more convenient short course had equal DFS and local failure rate compared with chemoradiation, and there was a trend toward improved OS. The short-course radiation has been more popular in Europe than in the United States, but these results may lead to increased usage to this method of radiation.
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