Division of Medical Oncology A, Department of Medicine, National Tumor Institute, Naples, Italy.

Capecitabine, an oral prodrug of fluorouracil (5FU), has shown efficacy in terms of progression-free and overall survival at least equivalent to standard folinic acid (leucovorin)-modulated intravenous 5FU bolus regimens in patients with metastatic colorectal cancer. Moreover, capecitabine has demonstrated a better tolerability profile, producing a significantly lower occurrence of severe stomatitis than 5FU plus folinic acid regimens, making this drug particularly attractive for treating elderly patients. In addition, capecitabine can be combined with other active drugs such as irinotecan or oxaliplatin. Indeed, the combination of capecitabine plus oxaliplatin (XELOX regimen) now represents a new standard of care for the metastatic disease and is also under evaluation in the adjuvant setting. The combination of new biological drugs, such as bevacizumab, with the XELOX regimen was shown to further prolong the time to progression of metastatic disease, and might reduce the risk of recurrence for those with resected colon cancer with poor risk factors. Cost-effectiveness analyses have demonstrated that, despite higher acquisition costs, capecitabine appears to be more cost effective than standard treatments for the management of colorectal cancer patients.

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Department of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-10-6, Ariake, Koto-ku, Tokyo, 135-8550, Japan, tomo.osako@jfcr.or.jp.

PURPOSE: We retrospectively evaluated the efficacy and safety of combination therapy of trastuzumab plus capecitabine in heavily pretreated patients with HER2-positive metastatic breast cancer (MBC). METHODS: Patients with HER2-positive MBC who had been administered the combination therapy between July 2003 and July 2006 at the Cancer Institute Hospital, Tokyo, were retrospectively reviewed. Capecitabine (828 mg/m(2)) was given twice daily for 3 weeks followed by a 1-week rest period; this was repeated every 4 weeks. Trastuzumab was given at 4 mg/kg as an initial loading dose intravenously, followed by 2 mg/kg weekly. We investigated objective response rate (ORR), clinical benefit rate (CBR), and time-to-treatment failure (TTF) according to the Response Evaluation Criteria in Solid Tumors guidelines. Adverse events were graded according to the National Cancer Institute, Common Toxicity Criteria, version 3.0. RESULTS: A total of 49 patients were assessed and median follow-up time of patients was 16.2 months (1.4-43.5 months). ORR was 16% (95% confidence interval: 7-30%) and CBR was 47% (95% confidence interval: 32-62%). Median TTF was 5.4 months. Common adverse effects were hand-foot syndrome, liver dysfunction, and bone marrow suppression. Grade 3 adverse events were observed in nine patients (18%). One patient (2%) suffered from symptomatic chronic heart failure, which improved after discontinuation of trastuzumab. CONCLUSIONS: The combination therapy of trastuzumab plus capecitabine is effective and tolerable for heavily pretreated patients with HER2-positive MBC.

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aMedical Oncology, Yale University School of Medicine, Section of Medical Oncology, New Haven, Connecticut, USA bOncology Unit, Third Department of Medicine, Athens Medical School, Sotiria General Hospital, Athens, Greece.

Xeloda (capecitabine), a thymidine phosphorylase activated fluoropyrimidine carbamate, is currently the only universally approved orally administered 5-fluorouracil (5-FU) prodrug. It belongs to a newer generation of orally administered fluoropyrimidines. It has been developed because of the clinical need for efficient, tolerable and convenient agents, which do not require continuous infusion. Capecitabine is not a cytotoxic drug in itself, but via a three-step enzymatic cascade, it is converted to 5-FU mainly within human cancer cells. While the drug compares favorably with 5-FU in patients with advanced or metastatic colorectal cancer and pretreated breast cancer, it also has an improved toxicity profile, mainly of gastrointestinal and dermatologic effects with a significantly lower incidence of grade 3/4 myelotoxicity compared with infusional 5-FU-based chemotherapy. Capecitabine’s selective activation within the tumor allows for less systemic toxicity events. A gradient of fluoropyrimidine toxicity is observed: high in the US and low in East Asia. In addition, there is a discrepancy in tolerance of dose among patients treated in the US vs. Europe. Although patients can take the drug orally in the convenience of their own home, the key to successful management of capecitabine is the clinician’s awareness of its severe, but low in incidence, adverse effects, and the patients’ education, emphasizing compliance with the treatment plan, prevention and timely recognition of its toxicities.

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