Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients.
OBJECTIVE
A multicenter phase II study evaluating efficacy, safety, and pharmacokinetics of ecteinascidin-743 (ET-743) in pretreated advanced soft tissue sarcoma patients.


METHODS
Patients received ET-743 1,500 microg/m(2) (24-hour intravenous infusion) every 3 weeks (group 1, 26 patients with one to two prior single agents or one previous combination chemotherapy; group 2, 28 patients with three or more prior single agents or two or more previous combination chemotherapies). Results Patients (30 women, 24 men) had a median age of 48 years (range, 22 to 71 years); 41% had leiomyosarcoma (eight of 22 of uterine origin), a median of two involved organs (range, one to four), and 93% had documented progressive disease at study entry. Patients received a median of three cycles (range, one to 20); 28% received six or more cycles. Fifty-two patients were assessable for response (WHO criteria): two partial responses, four minor responses, and nine with stable disease (> or = 6 months). Three patients were rendered tumor free after surgery. Median progression-free survival was 1.9 months (range, 0.69 to 17.90 months); 24% of patients were progression free at 6 months. Median survival was 12.8 months, with 30% of patients alive at 2 years. Four patients withdrew because of treatment-related toxicity. Two treatment-related deaths occurred (renal failure and febrile neutropenia, and rhabdomyolysis and decompensated cirrhosis, respectively) that were probably related to protocol eligibility violations. Reversible grade 3 to 4 AST or ALT occurred in 50% of patients and grade 3 to 4 neutropenia occurred in 61% of patients, with six episodes of febrile neutropenia. Nausea, vomiting, and asthenia were prevalent but mild and manageable.


CONCLUSIONS
With a 4% overall response rate (95% CI, 0.5 to 12.8) and an 11% rate of third-party-verified tumor regression (overall response rate + minor response), ET-743 has a 24% 6-month disease progression control rate, confirming evidence of antitumoral activity and a manageable safety profile in patients experiencing disease progression with pretreated soft tissue sarcoma.
Hôpital St Louis, Unité d'Oncologie Médicale, 1 av. Claude Vellefaux, 75010 Paris, France. jean-louis.misset@sls.ap-hop-paris.fr
A
A
Yovine
M
M
Riofrio
J Y
JY
Blay
E
E
Brain
J
J
Alexandre
C
C
Kahatt
A
A
Taamma
J
J
Jimeno
C
C
Martin
Y
Y
Salhi
E
E
Cvitkovic
J L
JL
Misset
D000328:Adult; D000368:Aged; D001682:Biological Availability; D001707:Biopsy, Needle; D004149:Dioxoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D016879:Salvage Therapy; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; D016896:Treatment Outcome
D004149:Dioxoles; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin