Capecitabine Replaces 5-FU in Asian Metastatic Gastric Cancer Investigations

NEW ORLEANS-Oral capecitabine(Drug information on capecitabine) (Xeloda) is active and well tolerated in first-line regimens for advanced gastric cancer, according to two recent studies from China and Korea. In both trials, investigators used oral capecitabine as a replacement for 5-fluorouracil (5-FU) in patients with previously untreated metastatic disease. In one study, Chinese investigators evaluated the combination of capecitabine and cisplatin(Drug information on cisplatin) (Platinol) in a multicenter trial (abstract 4047). Currently, infusional 5-FU/cisplatin is standard of care in China for patients with advanced gastric cancer. In the other study, a single-center phase II trial, Korean investigators evaluated capecitabine/docetaxel (Taxotere), with docetaxel(Drug information on docetaxel) given on a weekly schedule (abstract 4057). Positive results had previously been reported for that combination with docetaxel given on an every-3-weeks schedule. However, weekly docetaxel may be just as effective and safer, noted investigator Hark K. Kim, MD, PhD, of the Center for Gastric Cancer, National Cancer Center, Gyeonggi, Korea. Capecitabine may improve conve- nience, as well. "Replacing IV 5-FU with oral capecitabine in this combination minimizes the time needed at the clinic, allowing patients the convenience and comfort of home-based care," Dr. Kim and colleagues said in a poster presentation. Korean Study: Capecitabine/Docetaxel The Korean group reported an overall response rate of 40% (95% confidence interval [CI], 26% to 55%), median time to progression of 4.5 months, and median overall survival time of 12 months in a study of 55 patients with previously untreated metastatic gastric cancer who received weekly docetaxel (36 mg/m², 60- minute infusion on days 1 and 8) plus capecitabine (1,000 mg/m² twice daily on days 1 to 14). The combination had a "predictable and manageable"safety profile. There were no grade 4 adverse events, and the grade 3 adverse events were "modest," Dr. Kim said, except for stomatitis (26%). The main grade 3 adverse events included neutropenia (36%) and leukopenia (18%). Less than 5% of patients experienced grade 3 hand-foot syndrome. The most common grade 1/2 adverse events were anorexia, alopecia, nausea, and fatigue. "Until now, standard chemotherapy for gastric cancer was inpatientbased infusion therapy," Dr. Kim said. "Capecitabine/docetaxel allows patients to be treated as outpatients, with comparable efficacy and feasible toxicity, which can be shown by the quite long overall median survival compared with previous therapies." Every-3-weeks docetaxel plus capecitabine was evaluated previously. Park et al from the Korea Institute of Radiological and Medical Science, Seoul, reported a phase II study of docetaxel (75 mg/m² every 21 days) plus capecitabine (1,250 mg/m² twice daily) in 42 patients with advanced gastric cancer (Br J Cancer 90:1329- 1333, 2004). For 38 evaluable patients, the overall response rate was 60% (95% CI, 45% to 74%), with a median progression- free survival time of 5.2 months and a median overall survival time of 10.5 months. The most common grade 3/4 adverse events were hand-foot syndrome (50%), neutropenia (15%), and leukopenia (12%). In that study, Dr. Park and colleagues said that lower doses of both docetaxel and capecitabine could reduce the rate of specific toxicities, such as handfoot syndrome. It is not clear why overall survival of 12 months was achieved in the study of weekly docetaxel plus capecitabine reported by Dr. Kim and colleagues at ASCO. However, Dr. Kim noted that all study enrollees began with good performance statuses, and about 60% of patients received second-line chemotherapy with agents such as irinotecan(Drug information on irinotecan) and cisplatin, with about 25% entering into a second remission. In any case, these efficacy and safety results suggest weekly docetaxel plus capecitabine may be "a good option for first-line chemotherapy for metastatic gastric cancer patients," he said. Chinese Study: Capecitabine/Cisplatin The Chinese group, led by principal investigator Maolin Jin, MD, of the Clinical Cancer Hospital, affiliated with Beijing University, Beijing, reported on an open-label, multicenter study of capecitabine (1,000 mg/m² twice daily on days 1 to 14) plus fractionated cisplatin (20 mg/m² on days 1-5 every 3 weeks). With an overall response rate of 45% and few moderate-to-severe adverse events, capecitabine/fractionated cisplatin is "an effective first-line treatment for Chinese patients with advanced gastric cancer," according to Dr. Jin. Time to progression and overall survival were not reported for the ongoing trial, which to date has enrolled 130 patients at 28 centers. The 45% response rate is slightly lower than the 55% response rate previously reported by Korean investigators in a phase II study of capecitabine/ cisplatin (Ann Oncol 13:1893-1898, 2002). However, the Korean study used higher doses of both capecitabine and cisplatin, resulting in higher toxicity. More importantly, replacing 5-FU/ cisplatin with capecitabine/cisplatin may offer specific advantages: "The capecitabine/cisplatin regimen offers the potential for convenient outpatient delivery without the unwanted risks, discomfort, and costs associated with infusional therapy," the investigators said. The Chinese trial is expected to be completed in June 2005.