NUTLEY, N.J., Oct. 2 /PRNewswire/ -- Roche announced that the latest results from an international, Phase III study showed the chemotherapy combination XELOX (Xeloda + oxaliplatin) to be as effective -- in terms of progression-free survival (PFS) -- as the current standard treatment, FOLFOX-4 (infused 5-FU/leucovorin + oxaliplatin), in the treatment of advanced (metastatic) colorectal cancer.
The data, presented for the first time today at the 31st European Society for Medical Oncology (ESMO) Congress, also showed that adding the anti-angiogenic Avastin to chemotherapy (XELOX and FOLFOX-4) significantly improves PFS compared to chemotherapy alone.
“This data is encouraging for both doctors and patients. Based on the results, XELOX may offer a new treatment option for metastatic colorectal cancer that is as effective as the current standard treatment,” said Professor Jim Cassidy, co-lead investigator for the study and Cancer.
Research UK Professor of Oncology and Chair of Medical Oncology, Beatson Oncology Centre, at the University of Glasgow, Scotland. “And, because XELOX includes oral Xeloda, it offers patients the added benefit of less hospital or clinic time, with patients receiving a two-hour infusion of oxaliplatin followed by taking Xeloda tablets at home, instead of a continuous 48-hour infusion of FOLFOX-4. The study also shows that by adding Avastin, we can further improve progression-free survival times.”
Several additional studies are under way investigating the potential of Xeloda in combination with other therapies to treat both adjuvant and advanced colorectal cancer.
“As part of the largest Phase III colorectal cancer registration program ever, this study reinforces the promise of Xeloda as a foundational treatment for patients with colorectal cancer,” said Lars Birgerson, Vice President, Medical Affairs, Roche. “We are excited to see favorable data supporting the use of Xeloda in combination with Avastin, and look forward to presenting the final study results at an upcoming scientific meeting.”
Overall survival data are currently immature and are expected to be presented at a future oncology conference. No new safety findings related to Avastin or Xeloda were observed in the trial.
Colorectal cancer is the third most common cancer in the United States. The American Cancer Society estimates that in 2006, more than 148,000 people in the U.S. will be diagnosed and about 55,000 people will die from the disease.
About Study NO16966
The NO16966 trial is a large, randomized, international, Phase III trial of 2,035 advanced colorectal cancer patients that initially compared first-line XELOX (Xeloda + oxaliplatin) versus FOLFOX-4 (intravenous bolus and infusional 5-fluorouracil + oxaliplatin). After release of Avastin data in colorectal cancer in 2003, the protocol was amended to investigate, using a 2 by 2 factorial design, XELOX + placebo versus XELOX + Avastin (7.5 mg/kg q3w) versus FOLFOX-4 + placebo versus FOLFOX-4 + Avastin (5.0 mg/kg q2w).
The primary objective of the study was to answer two questions: 1) whether the XELOX regimen is non-inferior to FOLFOX; and 2) whether the addition of Avastin to chemotherapy improved results compared to chemotherapy alone. The secondary endpoints included overall survival, overall response rates, time to, and duration of, response and safety profile.
The study showed that XELOX (Xeloda + oxaliplatin) is as effective as FOLFOX-4 (infused 5-FU + oxaliplatin) in terms of PFS (hazard ratio: 1.05; upper limit of the 95 percent confidence interval was below the non-inferiority margin of 1.23).
Adding Avastin to chemotherapy (FOLFOX-4 and XELOX) significantly improved PFS compared to chemotherapy alone (hazard ratio: 0.83); this means that adding Avastin to chemotherapy combination improves the chances of delaying progression of the disease by 20 percent.
No unexpected safety findings were identified for either XELOX or Avastin in this study. Grade 3/4 adverse events which occurred at a rate greater than 10 percent in any of the treatment arms were: diarrhea (FOLFOX-4, 11.2 percent of patients; XELOX, 20.2 percent of patients), neutropenia (FOLFOX-4, 43.8 percent of patients; XELOX 7.0 percent of patients) and neurosensory toxicity (FOLFOX-4, 16.5 percent of patients; XELOX, 17.4 percent of patients). The percentage of gastrointestinal perforations was 0.6 percent in the Avastin arms compared to 0.3 percent in the placebo group. Grade 3/4 arterial thromboembolic events occurred in 1.7 percent of patients vs. 1.0 percent respectively. Grade 3/4 proteinuria was reported for 0.6 percent of all patients receiving Avastin. Wound healing complications were not observed in a higher frequency than in the placebo group (0.1 percent vs. 0.3 percent).
About XELOX
XELOX is an abbreviation for a type of combination chemotherapy used to treat colorectal cancer; it contains Xeloda (capecitabine) plus oxaliplatin.
About XELODA (capecitabine)
Xeloda is the only FDA-approved oral chemotherapy for both metastatic breast cancer and adjuvant and metastatic colorectal cancer. Inactive in pill form, Xeloda is enzymatically activated within the body; when it comes into contact with a naturally occurring protein called thymidine phosphorylase, or TP, Xeloda is transformed into 5-FU, a cytotoxic (cell-killing) drug. Because many cancers have higher levels of TP than does normal tissue, more 5-FU is delivered to the tumor than to other tissue.
A clinically important drug interaction between Xeloda and warfarin has been demonstrated; altered coagulation parameters and/or bleeding and death have been reported. Clinically significant increases in prothrombin time (PT) and INR have been observed within days to months after starting Xeloda, and infrequently within one month of stopping Xeloda. For patients receiving both drugs concomitantly, frequent monitoring of INR or PT is recommended. Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy.
Xeloda is contraindicated in patients who have a known hypersensitivity to 5-fluorouracil, and in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. Xeloda is contraindicated in patients with severe renal impairment. For patients with moderate renal impairment, dose reduction is required
The most common adverse events (greater than or equal to 20%) of Xeloda monotherapy were diarrhea, nausea, stomatitis and hand-foot syndrome. As with any cancer therapy, there is a risk of side effects, and these are usually manageable and reversible with dose modification or interruption.
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world’s leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years, the Roche Group has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people’s health and quality of life. An employer of choice, in 2005, Roche was named one of Fortune magazine’s Best Companies to Work For in America, one of the Top 20 Employers (Science magazine), ranked as the No. 3 Best Company to Work For in NJ (NJ Biz magazine), the No. 1 Company to Sell For (Selling Power), and one of AARP’s Top Companies for Older Workers. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or www.roche.us.
Roche
CONTACT: Ginny Valenze of Roche, +1-973-562-2783,virginia.valenze@roche.com; or Daphne Hoytt of Manning Selvage & Lee forRoche, Office: +1-212-468-3558, Cell: +1-917-406-2779,daphne.hoytt@mslpr.com
