A phase II study of liposomal lurtotecan (OSI-211) in patients with topotecan resistant ovarian cancer.
OBJECTIVE
To determine the safety and efficacy of a novel topoisomerase I inhibitor, liposomal lurtotecan, in patients with topotecan resistant ovarian cancer.


METHODS
The trial was an open-label phase II study for patients stratified by resistance to either single agent topotecan or to a prior topotecan-containing regimen. Liposomal lurtotecan was delivered at a dose of 2.4 mg/m(2) on Days 1 and 8 of a 21-day cycle. Dose escalations and reductions were allowed based on hematologic toxicity. Patients were evaluated every two cycles for response to liposomal lurtotecan.


RESULTS
Twenty-two women were accrued, with 16 women resistant to single agent topotecan and 6 women resistant to topotecan given in combination with a second chemotherapy agent. Hematologic toxicity consisted of mild to moderate thrombocytopenia, anemia, and neutropenia with mild to moderate gastrointestinal toxicity and fatigue. There were no responses, although eight patients had stable disease.


CONCLUSIONS
Liposomal lurtotecan at this schedule demonstrates moderate hematologic toxicity and no evidence of clinical activity in a group of heavily pretreated women previously exposed to the topoisomerase I inhibitor topotecan. The study of this agent in alternative patient populations or with alternative schedules is ongoing.
Seiden
Michael V
MV
The Division of Medical Oncology, New York University, New York, NY 10016, USA. mseiden@partners.org
Muggia
Franco
F
Astrow
Allan
A
Matulonis
Ursula
U
Campos
Susanna
S
Roche
Maria
M
Sivret
Julia
J
Rusk
Jason
J
Barrett
Emma
E
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004337:Drug Carriers; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008081:Liposomes; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D019772:Topotecan / Q000494:pharmacology
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; C091719:lurtotecan; D019772:Topotecan; D002166:Camptothecin