Trabectedin for women with ovarian carcinoma after treatment with platinum and taxanes fails.
OBJECTIVE
To assess the efficacy and toxicity of the marine-derived alkaloid trabectedin (ET-743) in patients with advanced ovarian cancer refractory to or experiencing disease relapse after platinum- and taxane-based chemotherapy.


METHODS
Fifty-nine patients from four institutions either resistant (n = 30) or sensitive (n = 29) to prior platinum and taxanes were treated with a 3-hour infusion of trabectedin every 3 weeks. Patients were monitored weekly for toxicity and restaged every two cycles for response. Response was assessed according to Response Evaluation Criteria in Solid Tumors Group.


RESULTS
The peer-reviewed objective response rate in platinum-sensitive patients was 43% (95% CI, 23% to 65%) with an estimated median time to progression of 7.9 months (95% CI, 7.5 to 14.1 months); in platinum-resistant patients two partial responses were observed. Responses were durable for up to 12.9 months (median, 5 months). The predominant toxicities at the recommended dose of 1,300 microg/m(2) were neutropenia, asthenia, and self-limited increase of aminotransferases never requiring treatment interruption.


CONCLUSIONS
Trabectedin administered as a 3-hour infusion at 1,300 microg/m(2) is a safe new drug with promising activity in relapsed ovarian cancer, showing a 43% objective response rate in patients with platinum-sensitive disease, which favorably compares with other salvage treatments and warrants additional development either alone or in combination.
Sessa
Cristiana
C
Southern Europe New Drugs Organization Foundation, Via Visconti di Modrone 12, 20100 Milano, Italy. marsonis@sendo-org.it
De Braud
Filippo
F
Perotti
Antonella
A
Bauer
Jean
J
Curigliano
Giuseppe
G
Noberasco
Cristina
C
Zanaboni
Flavia
F
Gianni
Luca
L
Marsoni
Silvia
S
Jimeno
José
J
D'Incalci
Maurizio
M
Dall'ó
Elisa
E
Colombo
Nicoletta
N
D000328:Adult; D000359:Aftercare; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004149:Dioxoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000473:pathology; D016879:Salvage Therapy; D043823:Taxoids / Q000008:administration & dosage; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; D017211:Treatment Failure
D018906:Antineoplastic Agents, Alkylating; D001952:Bridged-Ring Compounds; D004149:Dioxoles; D007546:Isoquinolines; D043823:Taxoids; D044005:Tetrahydroisoquinolines; C080625:taxane; D000077606:Trabectedin; D002945:Cisplatin