News Release

New treatment for advanced colorectal cancer offers relief from tumor-related symptoms

Increase in survival may not be benefit, but drug offers important option where none existed

Peer-Reviewed Publication

Vanderbilt University Medical Center

CHICAGO — The addition of oxaliplatin to standard chemotherapy in patients with advanced colorectal cancer increases tumor response rate, lengthens time to tumor progression and offers a higher rate of relief from tumor-related symptoms, a new study finds.

The median survival for patients who received oxaliplatin in combination with 5-FU/leucovorin was approximately 1-2 months longer than for the patients who received either therapy alone. However, that increase in survival was not statistically significant, meaning it is possible that it occurred by chance.

"These results give us a clearer picture of the impact of oxaliplatin in patients with progressive, metastatic cancer," said Dr. Mace L. Rothenberg, principal investigator of the multi-center trial. "If benefits like delay in time-to-tumor progression and relief from tumor-related symptoms are important considerations, then the combination of oxaliplatin and 5-FU/leucovorin offers a meaningful option for these patients, who really didn't have other options before.

"However, the data suggest that superior survival may not be one of the benefits achieved with this therapy."

Rothenberg, Ingram Professor of Cancer Research and director of Phase I Drug Development at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., presented the results of the study at 39th annual meeting of the American Society of Clinical Oncology (ASCO).

In North America, the combination of irinotecan, bolus 5-FU and leucovorin has been the most commonly used first-line chemotherapy for patients with metastatic colorectal cancer. However, no standard option has been available to patients whose disease progressed after this first-line therapy.

This Phase III study enrolled 821 patients with advanced colorectal cancer whose disease had progressed during or shortly after first-line chemotherapy. Patients were randomly assigned to receive 5FU-leucovorin, a regimen known as " LV5FU2," oxaliplatin alone or a combination of the two, known as FOLFOX4.

The primary question the study was designed to address was impact on overall survival. Secondary endpoints were response rate (percentage of patients whose tumors decreased in size by 30 percent or better); time to tumor progression (period of time before tumors grew); relief from tumor-related symptoms such as pain, need for pain medication, weight loss and activity level; and safety. In comparison to the control group that received LV5FU2, the group of patients who received both FOLFOX4 experienced:

  • Increased response rate (9.6 percent vs. 0.7 percent)
  • Lengthened time to tumor progression (5.6 months vs. 2.6 months)
  • Higher rate of relief from tumor-related symptoms (28 percent of patients vs. 15 percent)

Both components of therapy — oxaliplatin and 5-FU/leucovorin — are needed to achieve this effect," Rothenberg said. "These results were not achieved with oxaliplatin alone."

As for safety, the study found that FOLFOX4 was associated with higher rates of nausea, vomiting, diarrhea, fever as a result of diminished white blood cell count, and numbness and tingling in the extremities. However, Rothenberg noted, these side effects tend to be predictable and manageable.

Last year, the U.S. Food and Drug Administration approved oxaliplatin given as part of the FOLFOX4 regimen, based on preliminary data from this trial, for second-line therapy after treatment with 5FU/leucovorin and irinotecan. At the time, survival data was not available.

Rothenberg's co-authors on the ASCO presentation include his Vanderbilt-Ingram colleague Dr. Jordan D. Berlin and Drs. Amit M. Oza, Brent G. Burger, John Marshall, Ramesh K. Ramanathan, Sunil Gupta, Carlos A. Garay, and Daniel G. Haller from Princess Margaret Hospital, Lombardi Cancer Center, University of Pittsburgh and the University of Pennsylvania Cancer Center, and Sanofi-Synthelabo Research, which markets oxaliplatin.

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The Vanderbilt-Ingram Cancer Center, a part of Vanderbilt University in Nashville, is the only Comprehensive Cancer Center designated by the National Cancer Institute in Tennessee, and one of only 39 nationwide. This designation, the highest ranking awarded to cancer centers by the world's foremost authority on cancer, recognizes research excellence in cancer causes, development, treatment and prevention, as well as a demonstrated commitment to community education, information and outreach. To learn more, please visit www.vicc.org.


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