Survival and long-term outcomes in children with hepatoblastoma treated with continuous infusion of cisplatin and doxorubicin

Abstract

Despite high survival rates, many survivors of hepatoblastoma develop late effects including ototoxicity and cardiomyopathy. With the goal of minimizing long-term toxicities, our institution treated hepatoblastoma with continuous infusion of doxorubicin and cisplatinum (PLADO), rather than short infusion or bolus dosing as used in other treatment protocols. This retrospective cohort study includes consecutive patients diagnosed between 1985 and 2007. Patients were scheduled for treatment with 6 cycles of continuous infusion of PLADO with resection after the third or fourth cycle. Audiograms and echocardiograms were obtained at baseline, after every 2 chemotherapy cycles and yearly after the completion of therapy. Fifty-five patients were treated (34 localized; 21 metastatic). Fifty-one patients received at least 1 cycle of PLADO. Median follow-up was 7.0 years (range, 0.11 to 17.8 y). Event-free and overall survival for these 51 patients were 72.2% (standard error 6.3%) and 75.6% (standard error 6.2%) respectively. Of the 38 survivors treated with cisplatin who had an audiogram during follow-up, 4 (11%) demonstrated severe (Brock grade 3/4) and 13 (34%) mild (Brock grade 1/2) hearing loss. At a median of 10.0 years (range, 5.0 to 13.0 y) after therapy, 2 of 41 (5%) patients who were still alive had evidence of cardiac dysfunction. Overall, continuous infusion of PLADO therapy resulted in survival rates consistent with those observed in intergroup studies, but rates of chronic cardiac and ototoxicity did not differ sufficiently from those observed after shorter infusion of PLADO therapy to warrant the use of continuous infusions.