Thus, further confirmative Phase III trials will be needed. Nausea and hand-foot syndrome were the most common side effects of treatment, and hematologic toxicity was limited to Grades 2 and 3. The mildness of the observed toxicity may be attributable to the less aggressive starting dose of capecitabine (1,000 17-AAG side effects mg/m2) used for this group of patients. The use of 1,000 mg/m2 capecitabine has become common in the treatment of patients with other malignancies, such as colorectal carcinoma; this reduced dose was suggested by Borner et al.,29 who also recommended the use of 1,000 mg/m2 twice daily when capecitabine is used in combination with oxaliplatin. Although impaired hepatic function can exacerbate toxicity or inhibit the efficacy of many agents, the presence of mild-to-moderate hepatic dysfunction had no clinically significant effect on the pharmacokinetics of capecitabine and its metabolites.
17 This finding suggests that the CapGem regimen may be useful for patients with hepatobiliary carcinoma, including patients with mildly-to-moderately impaired hepatic function. Further research in this area should be directed at finding the best cytotoxic agent for combination with capecitabine or gemcitabine, or altering the dose intensity or route of administration in advanced gallbladder cancer. A larger trial of gemcitabine combined with cisplatin compared with CapGem needs to be conducted. Also, the role of the CapGem combination as an adjuvant treatment for suboptimally resected patients should be further pursued.
Hepatic encephalopathy (HE) is presented clinically as a combination of neuropsychiatric abnormalities characterized by alterations in mental status, personality, intellectual function, and changes in neuromuscular activity. It is frequently observed in those with both acute liver failure and liver cirrhosis.1 The pathogenesis of the syndrome is complex, but ammonia produced by intestinal bacteria is known to play an important role in its pathogenesis. The treatment of HE has focused on reducing both the production and absorption of gut-derived ammonia. Presently, non-absorbable disaccharides and antibiotics are the mainstay of therapy.2,3 However, currently used drugs have several limitations. For example, neomycin, a poorly-absorbed aminoglycoside may cause nephrotoxicity and ototoxicity,3 and lactulose treatment may be complicated by excessive diarrhea and abdominal pain.
4,5 Rifaximin (4-deoxy-4′-methylpyrido-(1′,2′-1,2)-imidazo-(5,4C)-rifamycin SV) is a derivative of rifamycin, which acts by inhibiting bacterial ribonucleic acid (RNA) synthesis. Rifaximin is virtually unabsorbed after oral administration and exhibits broad spectrum antimicrobial activity against both aerobic and anaerobic gram-positive Cilengitide and gram-negative microorganisms within the gastrointestinal tract.6 During the past decade, several European studies have proved the efficacy of rifaximin for the treatment of HE in Caucasian patients.