OXALIPLATIN USEFUL FOR OLDER PATIENTS WITH STAGE III COLORECTAL CANCER

January 22 (Orlando, Florida) — In contrast to some previous studies that found no benefit with newer chemotherapy regimens in elderly colorectal cancer patients, a randomized phase 3 trial showed better outcomes with adjuvant capecitabine and oxaliplatin (XELOX) than with standard 5-fluorouracil and leucovorin (5-FU/LV). The results came from a subanalysis of the NO16968 study, which compared adjuvant XELOX with standard chemotherapy in stage III patients.

"Half of all newly diagnosed colon cancer patients are over 70 years old and they are frequently not offered the same care as younger patients," said Daniel G. Haller, MD, the Deenie Greitzer Professor of Gastrointestinal Oncology at the University of Pennsylvania's Abramson Cancer Center in Philadelphia.

He presented his findings here at a press briefing as part of the 2010 Gastrointestinal Cancers Symposium. The annual meeting is cosponsored by the American Gastroenterological Association, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology, and the Society of Surgical Oncology.

"The use of newer chemotherapy drugs in the adjuvant setting for older patients with stage III colon cancer has been a topic of controversy, and these findings contradict conclusions from 2 recent studies," he noted. An analysis of the ACCENT database presented at ASCO 2009 (McCleary NAJ et al: Abstract 4010) found no additional benefit with newer oxaliplatin- or capecitabine-based regimens over 5-FU/LV in patients 70 years and older. Similarly, in the recently reported MOSAIC trial (J Clin Oncol 2009;27:3109-3116), adjuvant treatment with oxaliplatin and 5FU/LV did not offer additional benefits in elderly patients, he said.

"These data have prompted some clinicians to decide against using these drugs for their older patients," he said. In addition, on the basis of these studies, German clinical guidelines were revised, and at least 1 European trial was amended to exclude patients older than 70 years, he said. "We felt the need to mine our XELOX database to see if the elderly subgroup benefited in our study," he told journalists.

The study consisted of 1886 patients with stage III colon cancer who were randomly assigned to receive XELOX or 5-FU/LV after surgery. After a median follow-up of 57 months, analysis of 3-year disease-free survival found the effectiveness of XELOX to be similar for both the younger and older age groups.

Overall, 3-year disease-free survival was 71% for the XELOX group and 67% for the 5-FU/LV group, a difference that was statistically significant, Dr. Haller said. Patients younger than 70 years of age (n = 1477) receiving XELOX had a 3-year disease-free survival of 72%, compared with 69% for those receiving the standard regimen (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.66 - 0.94). For those 70 years or older (n = 409), disease-free survival was 66% and 60%, respectively (HR, 0.87; 95% CI, 0.63 - 1.18), Dr. Haller reported.

In response to a journalist's question, Dr. Haller acknowledged that the confidence intervals crossed 1.0 for the elderly patients and therefore lacked statistical significance. "What we were looking at were trends," he explained. "In the subgroup over 70, we were down to 400 patients, only 200 per arm, so this affects the hazard ratio."

Nevertheless, Dr. Haller believes the data are strong enough to "challenge" the MOSAIC findings. Although NO16968 is one of largest trials in the adjuvant setting, he pointed out that MOSAIC looked at only about 1200 patients and had a larger proportion of low-risk stage II patients, who derive questionable benefit from any chemotherapy.

He added that he anticipates a "vigorous debate" over the findings. "My concern is that, based on one 10-minute presentation at ASCO last year, physicians went back to their practices and stopped treating patients in their early 70s [with XELOX]."

"We conclude that, in addition to 2 other 5-FU/oxaliplatin regimens, XELOX is a new standard of care, regardless of age," he said. "With the oral capecitabine, treatment is more convenient, requires the fewest physician visits of any combination, and spares the patient the need for a surgically implanted access device and infusion pump."

Press briefing moderator Robert Sticca, MD, professor of surgery at North Dakota School of Medicine and Health Sciences in Grand Forks, called the findings "an important addition to our current knowledge" about adjuvant regimens in elderly patients." He added: "This is convincing, as the numbers in the study are very impressive."

Dr. Haller reports relationships with Sanofi-Aventis and Hoffmann-La Roche. Dr. Sticca has disclosed no relevant financial relationships.

2010 Gastrointestinal Cancers Symposium (GICS): Abstract 284. Presented January 22-25, 2010.