Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer.
OBJECTIVE
The objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy.


METHODS
Women > or = 18 years, stratified by performance status (0 to 1 v 2) and platinum sensitivity, were randomly assigned to receive an intravenous infusion of PLD 30 mg/m(2) followed by a 3-hour infusion of trabectedin 1.1 mg/m(2) every 3 weeks or PLD 50 mg/m(2) every 4 weeks. The primary end point was progression-free survival (PFS) by independent radiology assessment.


RESULTS
Patients (N = 672) were randomly assigned to trabectedin/PLD (n = 337) or PLD (n = 335). Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD (hazard ratio, 0.79; 95% CI, 0.65 to 0.96; P = .0190). For platinum-sensitive patients, median PFS was 9.2 months v 7.5 months, respectively (hazard ratio, 0.73; 95% CI, 0.56 to 0.95; P = .0170). Overall response rate (ORR) was 27.6% for trabectedin/PLD v 18.8% for PLD (P = .0080); for platinum-sensitive patients, it was 35.3% v 22.6% (P = .0042), respectively. ORR, PFS, and overall survival among platinum-resistant patients were not statistically different. Neutropenia was more common with trabectedin/PLD. Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative. Hand-foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone.


CONCLUSIONS
When combined with PLD, trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer.
University of California at Irvine (UCI) and UCI Medical Center, Orange, CA 92868-3298, USA. bjmonk@uci.edu
Bradley J
BJ
Monk
Thomas J
TJ
Herzog
Stanley B
SB
Kaye
Carolyn N
CN
Krasner
Jan B
JB
Vermorken
Franco M
FM
Muggia
Eric
E
Pujade-Lauraine
Alla S
AS
Lisyanskaya
Anatoly N
AN
Makhson
Janusz
J
Rolski
Vera A
VA
Gorbounova
Prafull
P
Ghatage
Mariusz
M
Bidzinski
Keng
K
Shen
Hextan Yuen-Sheung
HY
Ngan
Ignace B
IB
Vergote
Joo-Hyun
JH
Nam
Youn Choi
YC
Park
Claudia A
CA
Lebedinsky
Andrés M
AM
Poveda
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004149:Dioxoles / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D013280:Stomatitis / Q000139:chemically induced; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000009:adverse effects; D000077606:Trabectedin; D016896:Treatment Outcome
D004149:Dioxoles; D044005:Tetrahydroisoquinolines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000077606:Trabectedin