The U.S. Food and Drug Administration announced today that it had approved oxaliplatin to treat patients whose metastatic colorectal cancer has progressed after standard chemotherapy. The approval was based on data from a multi-center trial in the U.S. and Canada, led by Dr. Mace L. Rothenberg, which demonstrated that adding oxaliplatin to standard chemotherapy was better than either one alone at shrinking tumors and keeping them in check.
"Until now, there was no known effective therapy for people whose colorectal cancer progressed following front-line therapy," said Rothenberg, Associate Ingram Professor of Cancer Research and associate professor of Medicine. "Now we have an option for these patients."
Colorectal cancer is the second leading cancer killer in the United States, affecting nearly 150,000 people each year and claiming more than 46,000 lives.
Colorectal cancer is largely curable if caught early, when a tumor is still confined to the colon or rectum. About 90 percent of patients diagnosed at this stage will be alive five years later. However, just more than a third of colorectal cancers are caught at that stage, according to the American Cancer Society.
If the cancer has spread regionally to nearby organs or lymph nodes, five-year survival drops to 64 percent. And for patients with metastatic disease - whose cancer has spread to distant sites - five-year survival plummets to only about 8 percent.
"It is in the metastatic setting, among patients who have failed previous chemotherapy, that this trial demonstrated a benefit in terms of tumor shrinkage and time to tumor progression," Rothenberg said.
Oxaliplatin, which works by interfering with the copying of DNA as cells divide, was approved in 1996 for use in France, where its manufacturer is based. It has since been approved in other countries in Europe, Central and South America and Asia.
The study that Rothenberg designed and led enrolled patients whose metastatic colorectal cancer had progressed after treatment with a combination of irinotecan, fluorouracil (5-FU) and leucovorin. It compared three groups of patients: those who were randomly assigned to receive 5-FU/leucovorin alone, oxaliplatin alone or a combination of the therapies.
The application for FDA approval was based on analyzed data from 463 patients. The study showed that tumors shrank among more of the patients who received both oxaliplatin and 5-FU/leucovorin compared to the other two groups. In addition, patients who received both therapies also experienced a longer time before their tumors grew.
Specifically, the tumor response rate was 9 percent among patients receiving the combination therapy compared to 0 percent and 1 percent for 5FU/leucovorin alone and oxaliplatin alone. Tumor response is defined as the proportion of patients whose tumors shrank by at least 30 percent and whose shrinkage lasted for at least four weeks.
The median time to tumor progression among patients getting the combination therapy was 4.6 months, compared to 2.7 and 1.6 months for 5-FU/leucovorin alone and oxaliplatin alone.
Further follow-up is needed before investigators will know whether survival rates will differ among the three groups. It is hoped that the impact on tumor response and time to progression will translate into a reduction in tumor-related symptoms, such as pain, weight loss, and fatigue, but that too is still being evaluated.
Oxaliplatin can have a toxic effect on the nerve endings that may result in an acute or cumulative pattern of side effects, most often numbness or tingling in the hands, feet, mouth or throat. Other side effects may include nausea, diarrhea, anemia, increased risk of bleeding or infection or allergic reaction, according to the FDA's announcement of oxaliplatin's approval.
Rothenberg noted that the approval of oxaliplatin was another in a line of advances for colorectal cancer patients. "When I was in medical school 20 years ago," Rothenberg said, "the median survival for these patients was six months. Today, it is 18 months. I can't think of any other solid tumor in which h the survival gains have been as great. New drugs, such as oxaliplatin and irinotecan, combined with 5-FU and leucovorin, have a played a large role in that advance."
New trials have begun to test oxaliplatin in patients with locally advanced disease and as a front-line therapy.
Colorectal cancer is also largely preventable through proper screening for and removal of the precancerous growths called polyps. It is recommended that everyone age 50 and over undergo regular screening, which may include fecal occult blood test, sigmoidoscopy or colonoscopy. Such screening should begin earlier in individuals with a strong family history of the disease.
The Vanderbilt-Ingram Cancer Center is the only Comprehensive Cancer Center designated by the National Cancer Institute in Tennessee, and one of only 41 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.