Capecitabine in the Treatment of Advanced Gastric Cancer

Jae-Lyun Lee; Yoon-Koo Kang

Disclosures

Future Oncol. 2008;4(2):179-198. 

In This Article

Abstract and Introduction

Abstract

Although the role of systemic chemotherapy has been established for the treatment of advanced gastric cancer, the prognosis of these patients remains poor, with a median overall survival of less than 1 year. Based on the results of several randomized Phase III trials, 5-fluorouracil continuous infusion plus cisplatin, with or without epirubicin, has become the global reference regimen for this patient population. However, treatment with fluorouracil infusion requires either frequent hospitalizations or the use of a central venous access device, harboring potential complications. Capecitabine, a tumor-activating oral prodrug of fluorouracil, may be more advantageous in terms of patient convenience, safety and efficacy. Two recent randomized Phase III trials have shown that capecitabine could replace infusional fluorouracil in cisplatin-based regimens. Furthermore, Phase II trials have shown that many other capecitabine-based doublet or triplet chemotherapy regimens incorporating newer cytotoxic agents are active and well tolerated. Many promising biological agents are now being tested in Phase III trials, incorporating capecitabine combinations as control arms, in patients with advanced gastric cancer.

Introduction

Gastric cancer is the fourth most common cancer worldwide, with an estimated 934,000 new cases per year, and the second most common cause of worldwide cancer deaths, with an estimated 700,000 deaths annually.[1] Geographically, the incidence and prevalence rates are higher in Asia, Eastern Europe and South America than in Western Europe and North America.[2] While the overall incidence of gastric cancer in Western countries has steadily decreased, that of gastroesophageal junction and cardiac adenocarcinomas, which have different etiologic and biologic features, has increased annually.[3,4]

Although improvements in early diagnosis have increased the number of curative resections, local and distant relapses are common, even after complete resection. In the USA, adjuvant 5-fluorouracil (FU)-based chemoradiotherapy after limited lymph node dissection was regarded as standard treatment,[5] and in a UK study, perioperative epirubicin, cisplatin and 5-FU (ECF) chemotherapy significantly improved survival after extended lymph node dissection.[6] Despite tremendous efforts to improve the clinical outcomes of patients curatively resected for gastric cancer, no definite conclusions concerning the efficacy of adjuvant chemotherapy were reached until the recent report of the Japanese Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC).[7] Even after optimal treatment of localized disease, most patients experience relapse. In addition, many patients present with locally advanced unresectable disease or have distant metastases when first diagnosed. In these patients, palliative chemotherapy has been found to improve the duration and quality of life more than high-quality supportive care alone.[8,9,10]

Capecitabine is an oral prodrug of 5-FU, widely used in the treatment of breast, colorectal, pancreas and upper gastrointestinal cancer. This review describes its pharmacology and assesses currently available clinical data on the efficacy and safety of capecitabine, as a single agent or in combination therapy, for the treatment of advanced gastric cancer (AGC).

Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

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