A phase II study evaluating the tolerability and efficacy of CAELYX (liposomal doxorubicin, Doxil) in the treatment of unresectable pancreatic carcinoma

Background: Preclinical studies of liposomal doxorubicin (CAELYX(TM)) have demonstrated significant inhibition of growth of human pancreatic cancer explants in nude mice. This study evaluated the efficacy of CAELYX(TM) in chemotherapy-naive patients with unresectable, histologically confirmed pancreatic carcinoma. Secondary endpoints were quality of life (QOL), time to progression and overall survival. Patients and methods: Twenty-two patients (median age 65) were enrolled. CAELYX(TM) was administered to the first five patients at a dose of 30 mg/m(2) three-weekly. Two of these patients were dose escalated to 50 mg/m(2) four-weekly. Subsequent patients were all treated on the latter schedule. Results: Two patients died after consenting to enter the study but before treatment was commenced and are not included in the analysis. Sixteen patients were evaluable for response. No objective responses were seen. Six patients had stable disease. One patient experienced grade 4 toxicity with palmar plantar dysaesthesia (PPE), but continued treatment after dose reduction and delay. Four patients experienced grade 3 stomatitis and two grade 3 nausea. Median survival from time of starting chemotherapy was 3.2 months (range 21 days to 19 months) and one year survival was 10%. Eight patients completed at least two EORTC QLQ C-30 questionnaires. There was no significant change in either global QOL or in any functional or symptom subscale score. Conclusion:No objective responses were seen with CAELYX in this study. CAELYX(TM) was however associated with stable disease, but data were inconclusive with regard to clinical benefit. It warrants further investigation in the context of combination trials.