Randomized phase III study of canfosfamide in combination with pegylated liposomal doxorubicin compared with pegylated liposomal doxorubicin alone in platinum-resistant ovarian cancer.
OBJECTIVE
To evaluate the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in platinum-resistant ovarian cancer (OC).


METHODS
Patients with platinum-refractory or -resistant (primary or secondary) OC were randomized to receive canfosfamide at 1000 mg/m² and PLD at 50 mg/m² intravenously or PLD alone at 50 mg/m2 intravenously on day 1 every 28 days until tumor progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Other end points were objective response rate and safety. The study was originally planned for 244 patients. The trial was temporarily placed on hold after 125 patients were randomized while the results of another trial were being reviewed and the sponsor decided not to resume enrollment. The interim analysis became the final analysis.


RESULTS
The median PFS was 5.6 months for canfosfamide + PLD (n = 65) versus 3.7 months for PLD (n = 60) (hazards ratio, 0.92; P = 0.7243). A preplanned subgroup analysis showed that 75 patients with platinum-refractory or primary platinum-resistant OC had a median PFS of 5.6 months for canfosfamide + PLD versus 2.9 months for PLD (hazards ratio, 0.55; P = 0.0425). Hematologic adverse events were 66% on the canfosfamide + PLD arm versus 44% on the PLD arm, manageable with dose reductions. Nonhematologic adverse events were similar for both arms. The incidence of palmar-plantar erythrodysesthesia and stomatitiswas lower on canfosfamide + PLD(23%, 31%, respectively) versus (39%, 49%, respectively) on PLD.


CONCLUSIONS
Overall median PFS showed a positive trend but was not statistically significant. The median PFS in the platinum-refractory and primary platinum-resistant OC patients was significantly longer for canfosfamide + PLD versus PLD. Canfosfamide may ameliorate the palmar-plantar erythrodysesthesia and stomatitis known to be associated with PLD. Further study of this active well-tolerated regimen in platinum-refractory and primary platinum-resistant OC is planned. This study was registered at www.clinicaltrials.gov: NCT00350948.
Vergote
Ignace
I
University Hospitals, Leuven, European Union. ignace.vergote@uz.kuleuven.ac.be
Finkler
Neil J
NJ
Hall
James B
JB
Melnyk
Ostap
O
Edwards
Robert P
RP
Jones
Marsha
M
Keck
James G
JG
Meng
Lisa
L
Brown
Gail L
GL
Rankin
Elaine M
EM
Burke
James J
JJ
Boccia
Ralph V
RV
Runowicz
Carolyn D
CD
Rose
Peter G
PG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005978:Glutathione / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017671:Platinum Compounds / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D017671:Platinum Compounds; C506643:liposomal doxorubicin; C107479:TER 286; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005978:Glutathione