A phase I and pharmacokinetic study of paclitaxel poliglumex and cisplatin in patients with advanced solid tumors.
OBJECTIVE
Determine the toxicity, maximum tolerated dose (MTD), and pharmacokinetics of paclitaxel poliglumex (PPX; CT-2103) in combination with cisplatin administered every 3 weeks.


METHODS
Forty-three patients with advanced solid tumors were treated at escalating doses of PPX with a fixed dose of cisplatin at 75 mg/m(2). Conjugated and unconjugated paclitaxel were measured in plasma and urine. Cisplatin, as total platinum content in urine, was also assayed.


RESULTS
Dose-limiting toxicities included neutropenia and neuropathy with a cycle 1 MTD of 210 mg/m(2). Conjugated taxanes had a prolonged half-life of >100 h. Nine patients had partial responses, and 19 had stable disease.


CONCLUSIONS
PPX is a water-soluble paclitaxel-polymer conjugate with a prolonged half-life and a limited volume of distribution. PPX/cisplatin showed good activity in a refractory patient population; however, cumulative neuropathy was a significant issue at high doses, suggesting that a lower dose may be appropriate for prolonged therapy.
Verschraegen
Claire F
CF
University of New Mexico Cancer Research and Treatment Center, 900 Camino de Salud, Albuquerque, NM 87131, USA. cverschraegen@salud.unm.edu
Skubitz
Keith
K
Daud
Adil
A
Kudelka
Andrzej P
AP
Rabinowitz
Ian
I
Allievi
Cecilia
C
Eisenfeld
Amy
A
Singer
Jack W
JW
Oldham
Fred B
FB
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D011099:Polyglutamic Acid; D017239:Paclitaxel; D002945:Cisplatin; C509139:paclitaxel poliglumex