Intraperitoneal administration of Taxol in the management of ovarian cancer.
The safety and pharmacology of the intraperitoneal administration of Taxol was evaluated by treatment of 25 patients (24 with ovarian cancer) on a phase I dose-escalation trial. The drug was delivered in 2 L of normal saline every 3 to 4 weeks, with a starting dose of 25 mg/m2. The dose-limiting toxicity was abdominal pain at Taxol doses greater than 125 mg/m2. A 3-log pharmacokinetic advantage for peritoneal cavity exposure to Taxol, compared to the systemic compartment, was demonstrated following intraperitoneal delivery. In addition, high levels of Taxol persisted within the cavity for more than 48 hours following a single treatment. Despite the major pharmacokinetic advantage for peritoneal cavity exposure, significant concentrations of Taxol were demonstrated within the systemic compartment after intraperitoneal treatment. Several patients exhibited clinical and laboratory evidence of an antitumor response. Further exploration of a possible role for the intraperitoneal administration of Taxol in the management of ovarian cancer appears indicated.
Markman
M
M
Department of Hematology/Medical Oncology, Cleveland Clinic Foundation, OH 44195.
Rowinsky
E
E
Hakes
T
T
Reichman
B
B
Jones
W
W
Lewis
J L
JL
Rubin
S
S
Curtin
J
J
Barakat
R
R
Almadrones
L
L
D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*
D017239:Paclitaxel