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

Overview of the Market

Although systemic chemotherapy for AGC is associated with a survival advantage of up to 6 months, as well as improvements in quality of life,[11] there has been no worldwide consensus regarding the chemotherapy regimen that should be used as standard first-line treatment. Based on the promising results of Phase II studies of a 5-day infusion of 5-FU and cisplatin every 3-4 weeks (FP),[12,13,14] several Phase III trials have compared FP with infusional 5-FU alone and with other 5-FU based combinations.[15,16,17] Although FP did not demonstrate significant overall survival (OS) benefit, it consistently showed superior overall response rates (ORR) and progression-free survival (PFS) or time to tumor progression (TTP), and has therefore become a standard reference regimen for the treatment of AGC in Korea and in many other countries.[15,17] Another standard regimen, ECF, used in the UK and Europe, consists of epirubicin plus cisplatin and continuous intravenous infusion of 5-FU. ECF has shown survival advantage compared with various nonanthracycline-containing FP combinations in Cochrane's meta-analysis,[11,18,19,20,110] although there is continuing controversy. The addition of docetaxel to FP (DCF), when compared with FP combination chemotherapy in a first-line setting, was recently shown to result in significantly higher response rates (37 vs 25%; p = 0.01) and superior TTPs (5.6 vs 3.7 months; p < 0.01).[21] However, DCF caused significant hematologic toxicity, including neutropenia of grade 3 or higher in 82% of patients, and febrile neutropenia in 29% of patients, which required the secondary prophylactic use of granulocyte-colony stimulating factor (G-CSF). Although the median OS was significantly longer in the DCF group than in the FP group (9.2 vs 8.6 months; p = 0.02), the survival difference did not have clinical significance. Based on these findings, FP with or without anthracycline has become one of the standard treatment options in patients with AGC. However, 5-FU infusion is cumbersome and inconvenient, requiring hospital admission or central venous catheters with portable infusion pumps. Newer orally available fluoropyrimidines, which avoid these limitations, have been emerging in clinical oncology ( Table 1 ).[22,23]

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