Treatment of liver toxicity in women undergoing adjuvant chemotherapy for breast cancer: A phase III, monocentric, prospective, randomised trial of ursodeoxycolic acid (UDCA) vs no treatment

Abstract

9060 Background: Liver toxicity during adjuvant chemotherapy (CT) represents one of the causes of treatment delay and dose reduction, with impairment of dose intensity and of final results. UDCA, a hydrophilic bile acid, has been reported to be effective in cholestasis. Aim: to evaluate the efficacy of UDCA (12 mg/kg/die) plus CT discontinuation vs CT discontinuation alone in the treatment of liver toxicity. Methods: The study provided two arms of randomization: discontinuation of CT and administration of UDCA at the dosage of 12 mg/kg/day or discontinuation of CT. CT was resumed at normalization of liver tests. Pts with liver metastases, acute or chronic hepatopathy, heart or kidney failure, or PS<70 were excluded. During a 3 year period, 118/305 pts developed CT-induced hepatotoxicity and were enrolled into the study. Logistic multiple models and Fisher test or χ2 test and the Mann-Whitney test were used. Results: Out the 118 pts, 66% were treated with CMF, 29% with Anthracyclines alone or in sequence with CMF and 5% with Anthracyclines and Taxanes. Liver toxicity occurred respectively in 37 pts after the 1st cycle, in 35 after the 2nd, in 15 after the 3rd, in 19 after the 4th, in 9 after the 5th and in 3 after the 6th. CT was definitely stopped in 8% of pts. CT was delayed of 1 week in 53%, of 2 wks in 31% and of 3 or more in 16%. 95% of pts had a hepatocytolitic damage and nobody purely cholestatic. G1 toxicity was observed in 34%, G2 in 57%, G3 in 9%. Pts were randomized in two groups of 59 pts each. UDCA group: 3 pts (5%) stopped CT and 11 (19%) had dose reduction. Control group: 6 pts (10%) stopped CT and 7 (12%) had dose reduction. No statistically significant difference between UDCA group and control group was noted both for dose reduction (p = 0.31) and for CT stop (p = 0.30), even if twice as many pts of the control group had to stop CT (6/59). No correlation between alcohol use and liver damage was noted. Conclusions: Most cases of liver toxicity are of low or intermediate grade. No statistically significant difference was found between UDCA and control, even if there was a positive trend in reducing liver toxicity, that can have a positive impact on the final results of adjuvant CT. No significant financial relationships to disclose.