Roche News
Novel Xeloda(R) Dosing Schedule May Offer Well-Tolerated Alternative for Treatment of Advanced Breast Cancer
"As we predicted using the Norton-Simon mathematical model — the basis for the dose dense approach to therapy that was pioneered at MSKCC — these results demonstrate that a biweekly regimen of capecitabine appears to be well-tolerated, at dosing levels that are higher than previously thought possible," said
Efficacy of the 7-on/7-off schedule using Xeloda is being determined in a Phase II clinical trial program in patients with advanced breast cancer and is also being tested in combination with Avastin(R) (bevacizumab).
Breast cancer is the most common cancer among women, other than skin cancer. According to the American Cancer Society (ACS), about 182,460 women in
About the Study
Prior to study initiation, the Norton-Simon mathematical model (Norton et al, AACR 2005) — which explores how the growth characteristics of a cancer affect response to chemotherapy — was applied to determine that the maximum impact of Xeloda treatment in breast cancer patients occurs after seven days. Based on this finding, the single-center, open-label phase I/II trial was designed to determine the maximum tolerated dose (MTD) of Xeloda administered orally for seven days, followed by a seven-day rest (7-on/7-off), in patients with advanced-stage breast cancer. MTD was defined as the highest dose for which the incidence of dose-limiting toxicity (DLT) is less than 33 percent. DLT was defined as grade 3/4 hematologic toxicity lasting greater than two weeks despite growth factor support, or any grade 3/4 nonhematologic toxicity.
The Phase I study dose escalation scheme was a standard "3+3" design, using flat dosing that begins at 1,500 mg twice daily and increases by 500 mg/dose level until the MTD is reached. All patients in a cohort were observed for 28 days before enrollment to the next level is permitted to monitor for delayed toxicity.
The study showed that the dose dense regimen was well-tolerated in patients with advanced breast cancer, allowing safe delivery of higher daily doses than routinely used in practice. Of the 21 patients recruited for the trial, 18 were treated with Xeloda and reached a maximum tolerated dose of 2,000 mg twice daily. There were no grade 4/5 toxicities and grade 3 toxicities (which included one dose-limiting incident of hand-foot syndrome at 2,000 mg twice daily and two at 2,000 mg/2,500 mg, and one dose-limiting incident of diarrhea at 2,000 mg/2,500 mg) were transient and medically manageable. The most frequently reported treatment-related grade 2/3 adverse events were hand-foot syndrome (29 percent), leukopenia/neutropenia (24 percent) and fatigue (19 percent).
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
All trademarks used or mentioned in this release are protected by law. Contacts: Ginny Valenze Roche Office: 973-562-2783 virginia.valenze@roche.com Daphne Hoytt Manning Selvage & Lee Office: 212-468-3558 Cell: 917-406-2779 daphne.hoytt@mslpr.com
SOURCE Roche
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