A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and oxaliplatin in patients with advanced solid tumors

Cancer Chemother Pharmacol. 2008 Aug;62(3):449-56. doi: 10.1007/s00280-007-0624-3. Epub 2007 Oct 25.

Abstract

Purpose: To evaluate the maximum tolerated doses (MTD) and the dose-limiting toxicities (DLT) of the combination of pegylated liposomal doxorubicin (PEG-LD), paclitaxel and oxaliplatin (L-OHP) administered every 2 weeks in patients with advanced solid tumors.

Methods: Thirty-nine pretreated patients with advanced solid tumors received escalated doses of PEG-LD (10-16 mg/m(2)), paclitaxel (100-120 mg/m(2)) and L-OHP (50-70 mg/m(2)) every 2 weeks. As one cycle of treatment was considered the administration of both drugs on days 1 and 15 of a 4-week cycle.

Results: The MTDs were PEG-LD 14 mg/m(2), paclitaxel 120 mg/m(2) and L-OHP 70 mg/m(2). Neutropenia was the DLT in all but one case with only one episode of febrile neutropenia and no toxic deaths. Four (4%) and 13 (12%) cycles were complicated by grades 4 and 3 neutropenia, respectively. Grades 2-3 fatigue and neurotoxicity occurred in 13 and 12% of cycles, respectively. Responses were observed in patients with breast, endometrial and ovarian carcinomas.

Conclusions: This is a quite well-tolerated regimen which merits further evaluation in phase II studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / pharmacokinetics
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacokinetics
  • Paclitaxel / therapeutic use

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Doxorubicin
  • Paclitaxel