Phase 3 randomised study of canfosfamide (Telcyta, TLK286) versus pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with platinum-refractory or -resistant ovarian cancer.
BACKGROUND
Canfosfamide HCl (CAN) is a glutathione analogue prodrug that is activated by glutathione S-transferase P1-1 and induces apoptosis. CAN is synergistic in vitro with carboplatin, paclitaxel and anthracyclines.


METHODS
Patients with platinum-refractory or -resistant ovarian cancer (OC) who had progressed on second-line therapy with pegylated liposomal doxorubicin (PLD) or topotecan (TOPO), were randomised between CAN 1000 mg/m(2) IV q 3 weeks or to either PLD 50mg/m(2) IV q 4 weeks or TOPO 1.5mg/m(2) IV d1-5 q 3 weeks.


RESULTS
About 461 patients were randomised after stratification for ECOG performance status, prior therapy, and bulky (>5 cm) disease. Groups were well balanced. In the control arm 58% and 42% were treated with PLD and TOPO, respectively. CAN was well tolerated with the most common grade 3-4 toxicities of 5% anaemia, 4% neutropaenia (no febrile neutropaenia), 4% thrombocytopaenia, and 7% vomiting. Progression-free survival (PFS) and overall survival (OS) were significantly higher in the control arm (p<0.001 and p<0.01, respectively). In a subgroup analysis PFS and OS tended to be higher with PLD than with TOPO.


CONCLUSIONS
CAN was well tolerated. This is the first randomised study showing an increased OS with third-line therapy. This might have important consequences for other recurrent OC trials.
Vergote
I
I
University Hospitals, Leuven, European Union, Gynecologic Oncology, Gasthuisberg, B-3000 Leuven, Belgium. Ignace.Vergote@uz.kuleuven.ac.be
Finkler
N
N
del Campo
J
J
Lohr
A
A
Hunter
J
J
Matei
D
D
Kavanagh
J
J
Vermorken
J B
JB
Meng
L
L
Jones
M
M
Brown
G
G
Kaye
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005978:Glutathione / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C506643:liposomal doxorubicin; C107479:TER 286; D011092:Polyethylene Glycols; D019772:Topotecan; D004317:Doxorubicin; D005978:Glutathione