Capecitabine with Gemcitabine for Advanced Pancreatic Cancer: Results from a Swiss Phase I/II Trial
Capecitabine with Gemcitabine for Advanced Pancreatic Cancer: Results from a Swiss Phase I/II Trial
Abstract & Commentary
Synopsis: Although gemcitabine has been proven to be of value in the treatment of advanced pancreatic cancer, remission rates remain low and survival is measured in weeks to months. Swiss investigators report the results from a phase I/II study of combined gemcitabine/capecitabine treatment. The trial resulted in a recommended dose and schedule for the combination and some optimism that the drugs will be shown to work synergistically for patients with advanced pancreatic cancer.
Source: Hess V, et al. J Clin Oncol. 2003;21:66-68.
There are preclinical studies that suggest that the addition of capecitabine to the current standard treatment for advanced pancreatic cancer (gemcitabine) would offer additional value with little risk. To test this clinically, Hess and collaborators from Switzerland performed a phase I/II trial in patients with advanced pancreatic cancer (APC).
Thirty-six chemotherapy-naïve patients with non-resectable or metastatic pancreatic carcinoma were treated with gemcitabine at a fixed dose of 1000 mg/m2 on days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally b.i.d. for 14 days, followed by a 1-week rest. Dose-limiting toxicity (DLT) occurred at a dose of 800 mg/m2 of capecitabine and consisted of myelotoxicity and mucositis. Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, Hess et al recommend a dose of capecitabine of 650 mg/m2 when used with gemcitabine at 1000 mg/m2 on days 1 and 8 of a 21-day cycle.
With regard to observed responses, in the 27 patients with measurable disease, there were 1 complete and 4 partial remissions. In addition, significant drops (> 50% from baseline value) of the tumor marker CA 19-9 occurred in 14 of the 24 assessable patients.
Comment by William B. Ershler, MD
The current standard regimen for patients with advanced pancreatic cancer is single-agent gemcitabine.1 Although the addition of infusional 5-flurouracil has not been shown to increase treatment efficacy,2,3 the potential role for capecitabine in combination with gemcitabine had not been previously reported specifically for pancreatic cancer patients.
This phase I/II report offers a reasonable dose and schedule for the much-needed phase III study, currently underway, in which the combination is compared to gemcitabine monotherapy. The suggested dose of capecitabine (650 mg/m2) is somewhat lower than has been reported in a larger phase I study that included pretreated patients with various types of tumors.4 In that report, capecitabine at 830 mg/m2 given b.i.d. for 21 days with gemcitabine at 1000 mg/m2 weekly on days 1, 8, and 15 of a 28-day cycle, was considered tolerable. Hess et al suggest that the lower acceptable dose might be an indication of an increased susceptibility to toxicity in patients with pancreatic cancer.
Although this is a phase I/II report with a primary goal of determining toxicity and recommended dose and schedule, there is some room for optimism that the combination will be better than gemcitabine given alone when subjected to a clinical trial. Of the 24 patients who had elevated CA19-9 prior to treatment, 14 had a more than 50% reduction with treatment. Such a reduction has been shown by others5 to be associated with increased survival, even in the absence of achieving imaging criteria for remission.
Pancreatic cancer is among the most resistant of all tumors encountered, and clinicians are constantly frustrated by the lack of effective treatment options. Thus, this preliminary report offers some room for cautious optimism that these 2 drugs will work synergistically in providing more quality time for patients with advanced pancreatic cancer. Small steps for little feet.
Dr. Ershler, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
References
1. Burris HA, et al. J Clin Oncol. 1997;15:2403-2413.
2. Cascinu S, et al. Br J Cancer. 1999;80:1595-1598.
3. Berlin JD, et al. Oncology. 2000;58:215-218.
4. Schilsky RL, et al. J Clin Oncol. 2002;20:582-587.
5. Halm U, et al. Br J Cancer. 2000;82:1013-1016.
Although gemcitabine has been proven to be of value in the treatment of advanced pancreatic cancer, remission rates remain low and survival is measured in weeks to months. Swiss investigators report the results from a phase I/II study of combined gemcitabine/capecitabine treatment.Subscribe Now for Access
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