title: Phase I study of paclitaxel poliglumex administered weekly for patients with advanced solid malignancies.
abstract: BACKGROUND
  Paclitaxel poliglumex (PPX, also called Xyotax or CT-2103) is a water soluble macromolecular drug conjugate that links paclitaxel with a biodegradable polymer, poly-L-glutamic acid. The recommended phase II dose of PPX every 3 week is 235 mg/m(2) administered over a 10-min infusion without premedication. This study was designed to determine the MTD and pharmacology of PPX administered weekly to patients with solid malignancies.
  
  
  METHODS
  The starting dose of weekly PPX was 20 mg/m(2). Each cycle consists of 6 weekly treatments with pharmacokinetics of PPX (the conjugated paclitaxel) and unconjugated paclitaxel obtained after the first and sixth dose. Three to six patients were enrolled at each dose level. Toxicity and response were assessed by the NCI Common Toxicity criteria version 2 and RECIST criteria, respectively.
  
  
  RESULTS
  Twenty-six patients were treated with PPX at the following dose levels: 20 mg/m(2) (five patients), 40 mg/m(2) (four patients), 60 mg/m(2) (four patients), 70 mg/m(2) (eight patients) and 80 mg/m(2) (five patients). Dose-limiting toxicities, consisting of grade 3 neutropenia, occurred in the 80 mg/m(2) cohort during cycle 1. Therefore, the dose recommended for phase II studies was 70 mg/m(2). In this cohort, a single dose-limiting event, consisting of diarrhea, was seen. Neuropathy and fatigue were the most common toxicities. No objective responses were noted. Pharmacokinetics was dose-proportional, and the degree of neutropenia related to drug exposure, but not to peak plasma concentration. There was no significant accumulation of conjugated or unconjugated paclitaxel with this dosing schedule.
  
  
  CONCLUSIONS
  The recommended dose of PPX for subsequent disease-directed studies is 70 mg/m(2) weekly.
authors.affiliation: Cancer Therapy and Research Center, San Antonio, TX, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Mita
authors.forename: Alain
authors.initials: A
authors.lastname: Mita
authors.forename: John
authors.initials: J
authors.lastname: Sarantopoulos
authors.forename: Chris H
authors.initials: CH
authors.lastname: Takimoto
authors.forename: Eric K
authors.initials: EK
authors.lastname: Rowinsky
authors.forename: Ofelia
authors.initials: O
authors.lastname: Romero
authors.forename: Patrizia
authors.initials: P
authors.lastname: Angiuli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Allievi
authors.forename: Amy
authors.initials: A
authors.lastname: Eisenfeld
authors.forename: Claire F
authors.initials: CF
authors.lastname: Verschraegen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011099:Polyglutamic Acid; D017239:Paclitaxel; C509139:paclitaxel poliglumex