A multicenter phase II study of the cryptophycin analog LY355703 in patients with platinum-resistant ovarian cancer.
LY355703 is a synthetic product structurally related to the cryptophycin family isolated from the blue-green algae, which exerts a potent destabilization of microtubules during mitosis. This study was performed to determine the activity of LY355703 in patients with platinum-resistant advanced ovarian cancer and to characterize its toxicity profile. Twenty-six patients were enrolled in this study. Resistant disease was defined as a platinum-free interval of <6 months from primary treatment or rechallenge. LY355703 (1.5 mg/m(2)) was administered intravenously on days 1 and 8, every 3 weeks, infused over 2 h. From 24 patients evaluable for response, three partial responses (12.5%) and seven disease stabilizations were registered (29.2%), for an overall clinical benefit of 41.7%. Fourteen patients (58.3%) experienced a progression of the disease during treatment. Among the 25 patients evaluable for toxicity, two episodes of grade 3 anemia (8%); one, grade 3 thrombocytopenia (4%); one, grade 4 elevation of creatinine (4%); and one, grade 3 hyperbilirubinemia (4%) were reported. LY355703 has a modest activity in patients with platinum-resistant advanced ovarian cancer. Nevertheless, the considerable rate of disease stabilization in the absence of serious adverse events in this poor-prognosis study population suggests that this novel cryptophycin may deserve further investigation in this setting.
D'Agostino
G
G
Department of Gynecologic Oncology, Catholic University of the Sacred Heart, Largo A. Gemelli, 8-00168 Rome, Italy.
del Campo
J
J
Mellado
B
B
Izquierdo
M A
MA
Minarik
T
T
Cirri
L
L
Marini
L
L
Perez-Gracia
J L
JL
Scambia
G
G
D000328:Adult; D000368:Aged; D047630:Depsipeptides / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007769:Lactams / Q000008:administration & dosage*; D007783:Lactones / Q000008:administration & dosage*; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D010984:Platinum / Q000627:therapeutic use*; D011379:Prognosis; D018570:Risk Assessment; D016037:Single-Blind Method; D016019:Survival Analysis; D016896:Treatment Outcome
D047630:Depsipeptides; D007769:Lactams; D007783:Lactones; D010984:Platinum; C114033:cryptophycin 52