Phase I trial of intrapleural docetaxel administered through an implantable catheter in subjects with a malignant pleural effusion.
BACKGROUND
Malignant pleural effusion (MPE) is a common complication in patients with advanced malignancy. This dose escalation phase I study was designed to determine the maximum tolerated dose of intrapleural docetaxel administered through an implantable catheter in subjects with MPE.


METHODS
Subjects with MPE (n = 15) with median age of 64.6 years and an Eastern Cooperative Oncology Group performance status of 0 to 2 at baseline were enrolled into four single dose levels of docetaxel administered intrapleurally after drainage of the pleural effusion and insertion of an intrapleural catheter. The study determined the pharmacokinetic properties, clinical response, and toxicity profile of intrapleural docetaxel.


RESULTS
All patients tolerated the therapy well and there were no significant toxicities. The majority of patients had a complete radiographic response. All patients receiving dose 100 mg/m2 or higher had a complete radiographic response. One dose-limiting toxicity was encountered in the dose 50 mg/m2. Pharmacokinetic data demonstrated peak plasma concentration of docetaxel between 30 minutes and 6 hours after infusion. Pleural exposure to docetaxel was 1000 times higher than systemic exposure.


CONCLUSIONS
Single-dose intrapleural administration of doxetaxel is well tolerated in patients with MPE with minimal toxicity. The excellent clinical responses in this study after treatment with intrapleural doxetaxel suggest that further investigation is warranted.
Jones
David R
DR
Department of Surgery, University of Virginia, Charlottesville, Virginia 22908-0679, USA. djones@virginia.edu
Taylor
Matthew D
MD
Petroni
Gina R
GR
Shu
Jianfen
J
Burks
Sandra G
SG
Daniel
Thomas M
TM
Gillenwater
Heidi H
HH
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002408:Catheters, Indwelling; D000077143:Docetaxel; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel