Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of theperitoneum

Background. Several studies have demonstrated liposomal doxorubicin (Doxil) to be an active antineoplastic agent in platinum-resistant ovarian cancer, with dose limiting toxicity of the standard dosing regimen (50 mg/m(2) q 4 weeks) being severe erythrodysesthesia ("hand-foot syndrome") and stomatit is. We wished to develop a more tolerable liposomal doxorubicin treatment r egimen and document its level of activity in a well-defined patient populat ion with platinum/paclitaxel-refractory disease. Methods and Materials. Patients with ovarian or fallopian tube cancers or p rimary peritoneal carcinoma with platinum/paclitaxel-refractory disease (st able or progressive disease following treatment with these agents or previo us objective response <3 months in duration) were treated with liposomal do xorubicin at a dose of 40 mg/m(2) q 4 weeks. Results. A total of 49 patients (median age: 60; range 41-81) entered this phase 2 trial. The median number of prior regimens was 2 (range: 1-6), Six (12%) and 4 (8%) patients experienced grade 2 hand-foot syndrome and stomat itis, respectively (no episodes of grade 3). One patient developed grade 3 diarrhea requiring hospitalization for hydration. Six (12%) individuals req uired dose reductions. The median number of courses of liposomal doxorubici n administered on this protocol was 2 (range: 1-12), Four of 44 patients (9 %) evaluable for response exhibited objective and subjective evidence of an antineoplastic effect of therapy. Conclusion, This modified liposomal doxorubicin regimen results in less tox icity (stomatitis, hand-foot syndrome) than the standard FDA-approved dose schedule. Definite, although limited, antineoplastic activity is observed i n patients with well-defined platinum- and paclitaxel-refractory ovarian ca ncer. (C) 2000 Academic Press.