Schedule-dependent paclitaxel tolerance/activity: data from a 7 day infusion phase I study with pharmacokinetics in paclitaxel refractory ovarian cancer.
Our objective was to determine the maximum tolerated dose (MTD) of paclitaxel when given as a 7 day continuous i.v. infusion, repeated every 3 weeks, and to evaluate the toxicity and the efficacy of such a schedule of administration as a salvage treatment in ovarian cancer patients pretreated and refractory to 3 or 24 h paclitaxel. Thirteen women were enrolled in this phase I trial. Four dose levels ranging from 105 to 157.5 mg/m2/cycle were explored. Two of four patients experienced dose-limiting febrile neutropenia at the dose of 157.5 mg/m2. No objective response was observed, although three patients experienced disease stabilization (five to six cycles), with regression of disease symptoms, two of them having sustained 50% or greater decrease in CA 125. We conclude that the MTD in this population was paclitaxel 140 mg/m2/7 days. Schedule-dependent mechanisms of resistance to paclitaxel could not be demonstrated in this clinical setting of heavily pretreated ovarian cancer patients.
Soulié
P
P
SMST, Hôpital Paul Brousse, Villejuif, France.
Trandafir
L
L
Taamma
A
A
Lokiec
F
F
Brain
E
E
Delord
J P
JP
Mita
A
A
Vannetzel
J M
JM
Cvitkovic
E
E
Misset
J L
JL
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D016879:Salvage Therapy; D013921:Thrombocytopenia / Q000139:chemically induced
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel