Phase II study of a cremophor-free, polymeric micelle formulation of paclitaxel for patients with advanced urothelial cancer previously treated with gemcitabine and platinum

Invest New Drugs. 2012 Oct;30(5):1984-90. doi: 10.1007/s10637-011-9757-7. Epub 2011 Oct 20.

Abstract

Introduction: Genexol-PM is a novel Cremophor® EL (CrEL)-free polymeric micelle formulation of paclitaxel. This multicenter phase II study was designed to evaluate the efficacy and safety of Genexol-PM monotherapy in patients with advanced urothelial carcinoma who developed disease progression after gemcitabine and cisplatin combination chemotherapy.

Patients and methods: Patients received Genexol-PM 240 mg/m(2) intravenously over 3 h every 3 weeks without premedication. Intra-patient dose escalation to 300 mg/m(2) was allowed during the second and subsequent cycles if pre-specified toxicities were not observed during the first cycle. The primary endpoint was response.

Results: Thirty-seven patients were enrolled in this study. Platinum-free interval was less than 6 months in 27 (73%) patients, and 24 (64%) were categorized as having intermediate or poor prognosis according to Bajorin's criteria. Of 34 evaluable patients, there were 7 responses (21%; 95% CI, 7-34%), including one complete response (CR), with a median response duration of 6.5 months (95% CI, 3.5-9.6 months). The median time to progression was 2.7 months (95% CI, 0.9-4.6 months) with a median overall survival of 6.5 months (95% CI, 5.0-8.0 months). The most common grade 3/4 non-hematologic toxicities were peripheral neuropathy (sensory type 5.9%; motor type 8.8%) and infection (5.9%). Grade ≥3 hematologic toxicities occurred in only one patient.

Conclusion: Genexol-PM was generally well tolerated and demonstrated sufficient antitumor activity to warrant further development when used as second-line chemotherapy after gemcitabine-cisplatin failure in patients with urothelial carcinoma (NCT01426126).

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Transitional Cell / drug therapy*
  • Chemistry, Pharmaceutical / methods
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Disease Progression
  • Drug Administration Schedule
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Micelles
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Paclitaxel / administration & dosage*
  • Paclitaxel / adverse effects
  • Paclitaxel / chemistry
  • Polyethylene Glycols / chemistry
  • Polymers / administration & dosage
  • Polymers / chemistry
  • Prognosis
  • Urologic Neoplasms / drug therapy*

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Micelles
  • Organoplatinum Compounds
  • Polymers
  • Deoxycytidine
  • cremophor
  • Polyethylene Glycols
  • Paclitaxel
  • Cisplatin
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT01426126