Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum.
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 stomatitis. We wished to develop a more tolerable liposomal doxorubicin treatment regimen and document its level of activity in a well-defined patient population with platinum/paclitaxel-refractory disease.


METHODS
Patients with ovarian or fallopian tube cancers or primary peritoneal carcinoma with platinum/paclitaxel-refractory disease (stable or progressive disease following treatment with these agents or previous objective response <3 months in duration) were treated with liposomal doxorubicin 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 stomatitis, respectively (no episodes of grade 3). One patient developed grade 3 diarrhea requiring hospitalization for hydration. Six (12%) individuals required dose reductions. The median number of courses of liposomal doxorubicin 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.


CONCLUSIONS
This modified liposomal doxorubicin regimen results in less toxicity (stomatitis, hand-foot syndrome) than the standard FDA-approved dose schedule. Definite, although limited, antineoplastic activity is observed in patients with well-defined platinum- and paclitaxel-refractory ovarian cancer.
Markman
M
M
Gynecologic Oncology Program, The Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, USA.
Kennedy
A
A
Webster
K
K
Peterson
G
G
Kulp
B
B
Belinson
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004337:Drug Carriers; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004890:Erythema / Q000139:chemically induced; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy*; D005260:Female; D005533:Foot Dermatoses / Q000139:chemically induced; D006229:Hand Dermatoses / Q000139:chemically induced; D006801:Humans; D008081:Liposomes; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000627:therapeutic use; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D013280:Stomatitis / Q000139:chemically induced; D013318:Stroke Volume / Q000187:drug effects
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D009944:Organoplatinum Compounds; D004317:Doxorubicin; D017239:Paclitaxel