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.
Monk
Bradley J
BJ
University of California at Irvine (UCI) and UCI Medical Center, Orange, CA 92868-3298, USA. bjmonk@uci.edu
Herzog
Thomas J
TJ
Kaye
Stanley B
SB
Krasner
Carolyn N
CN
Vermorken
Jan B
JB
Muggia
Franco M
FM
Pujade-Lauraine
Eric
E
Lisyanskaya
Alla S
AS
Makhson
Anatoly N
AN
Rolski
Janusz
J
Gorbounova
Vera A
VA
Ghatage
Prafull
P
Bidzinski
Mariusz
M
Shen
Keng
K
Ngan
Hextan Yuen-Sheung
HY
Vergote
Ignace B
IB
Nam
Joo-Hyun
JH
Park
Youn Choi
YC
Lebedinsky
Claudia A
CA
Poveda
Andrés M
AM
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