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

Safety & Tolerability

In clinical practice, capecitabine is known for its good patient tolerability even in the elderly.[75] As a single agent, it is well tolerated by patients, with the predominant grade 3 or higher toxicity being HFS,[40,47,48] an adverse event related to chronic fluoropyrimidine exposure. Several anecdotal reports and retrospective studies have suggested the effectiveness of pyridoxine (100-300 mg/day) in the treatment and prevention of HFS, and pyridoxine has been frequently prescribed in clinical practice for this purpose.[76] Although pyridoxine is considered safe, with no toxicities additional to those of chemotherapy, there are concerns regarding the possible negative effects of pyridoxine on the antitumor activity of cisplatin-based chemotherapy.[77] In a recent prospective randomized trial in 389 patients, pyridoxine (200 mg/day) had no effect on the treatment or prevention of HFS.[78] These findings suggest that patients treated with capecitabine be properly educated on treatment interruption and strict adherence to dose modification guidelines, which can reduce the incidence of severe HFS. Other grade 3 or higher non-hematologic toxicities have been observed in approximately 5% or fewer capecitabine-treated patients. Interestingly, diarrhea and vomiting, the DLT of the Phase I study in the USA and Europe, have been rarely reported in Asian studies of this drug.[33,44] Capecitabine is minimally myelosuppressive and it does not cause significant alopecia. There have been few treatment-related deaths in AGC patients. Cardiotoxicity is a well-known side effect of intravenous 5-FU infusion. Several case reports have described the occurrence of vasospastic angina in patients treated with capecitabine.[79,80,81] Although cardiac events were rarely reported in patients with colorectal cancer treated with capecitabine monotherapy and the incidence rates were estimated to be low, 0.7%, and similar to bolus 5-FU-leucovorin (1.0%),[80,82,83,84] the incidence could increase when combined with oxaliplatin or irinotecan, especially in patients with a history of ischemic heart disease.[85] Clinical and electrocardiographic manifestation of angina should prompt drug interruption.[80]

The toxicity of capecitabine combinations depends on the regimen, and is described in Table 1 , Table 2 , Table 3 and Table 4 . The most frequently observed grade 3/4 toxicities in patients treated with capecitabine plus cisplatin are nausea (10%) and neutropenia (28-38%) not complicated with infection. Severe thrombocytopenia (11%) and neuropathy (5-8%) are more commonly observed in patients treated with capecitabine plus oxaliplatin, with a lower incidence of neutropenia (8%) than observed in patients treated with capecitabine plus cisplatin. The predominant toxicities of capecitabine plus docetaxel are febrile neutropenia (2-9%) and diarrhea (5-11%), whereas the predominant toxicities of capecitabine plus irinotecan are diarrhea (15-17%) and neutropenia (20-24%).

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