Phase I study of weekly docetaxel and liposomal doxorubicin in patients with advanced solid tumors

Oncology. 2005;69(3):202-7. doi: 10.1159/000087908. Epub 2005 Aug 26.

Abstract

Purpose: To determine the maximum-tolerated doses (MTDs) and the dose-limiting toxicities (DLTs) of the weekly administration of docetaxel and pegylated liposomal doxorubicin (PEG-LD) in patients with advanced solid tumors.

Patients and methods: Forty-eight patients with solid tumors were enrolled in the study. Dose escalations of both drugs were given on a weekly basis for 3 consecutive weeks in cycles of 4 weeks. The starting dose for docetaxel was 20 mg/m(2)/week and for PEG-LD 6 mg/m(2)/week.

Results: The MTD was 35 mg/m(2)/week for docetaxel and 14 mg/m(2)/week for PEG-LD. The DLTs at this level were grade 3 diarrhea (n=1 patient) and grade 3 mucositis (n=2 patients). There was no grade 4 hematologic or non-hematologic toxicity. Grade 3 neutropenia and thrombocytopenia occurred only in 1 and 2 patients, respectively. The non-hematologic toxicity was also mild with grade 2/3 fatigue in 8 patients, grade 2/3 neurotoxicity in 4, grade 2/3 mucositis in 8, grade 2/3 diarrhea in 4 and grade 2/3 nausea and vomiting in 5 patients. Two (5.7%) complete and 6 (17%) partial responses (overall response rate=22.7%; 95% confidence interval 9.6--32.4%) were observed among 35 evaluable patients. In 12 (63%) of 19 patients with hormone-refractory prostate cancer, a decline in serum levels of prostate-specific antigen of >50% was observed.

Conclusions: The weekly administration of docetaxel with PEG-LD is a well-tolerated regimen that merits further evaluation.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibiotics, Antineoplastic / administration & dosage
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms / drug therapy
  • Docetaxel
  • Doxorubicin / administration & dosage*
  • Doxorubicin / adverse effects
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous
  • Liposomes
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neoplasms, Unknown Primary / drug therapy
  • Polyethylene Glycols
  • Prostatic Neoplasms / drug therapy
  • Stomach Neoplasms / drug therapy
  • Taxoids / administration & dosage*
  • Taxoids / adverse effects
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Liposomes
  • Taxoids
  • Docetaxel
  • Polyethylene Glycols
  • Doxorubicin