Phase I trial of motexafin gadolinium and doxorubicin in the treatment of advanced malignancies

Anne M. Traynor, James P. Thomas, Ramesh K. Ramanathan, Tarak D. Mody, Dona Alberti, George Wilding, Howard H. Bailey

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Purpose To assess the safety, maximum-tolerated dose (MTD), and dose-limiting toxicities (DLT), of motexafin gadolinium (MGd), given in combination with doxorubicin, in patients with advanced solid tumors. Study Design The combination of MGd and doxorubicin was administered every 28 days (cycle 1) and then every 21 days (subsequent cycles). The dose of MGd, given daily for 3 days, was escalated from 1.0 mg/kg/d to 3.3 mg/kg/d, while the dose of doxorubicin was held at 30 mg/m2. Results Fifteen patients received 37 cycles of treatment, for a median of 2 cycles per patient (range 0-6 cycles). Three patients (20%) completed 6 cycles of therapy. The MTD was identified as MGd, 2 mg/ kg/day and doxorubicin, 30 mg/m2. Dose limiting toxicities included grade 3 hypertension, pneumonia, bacteremia, and elevated GGT. Serious adverse events also included pulmonary embolism and urinary tract infection requiring hospitalization. There was no exacerbation of cardiac toxicity. No patients attained a response to treatment. Six patients (54%) had stable disease. The median time to disease progression, or to last assessment, was 49 days (range 8-195 days). Conclusions The combination of MGd and doxorubicin was fairly well tolerated. However, due to emerging preclinical data suggesting that MGd inhibits ribonucleotide reductase, further development of the combination of MGd plus doxorubicin is not recommended.

Original languageEnglish (US)
Pages (from-to)316-322
Number of pages7
JournalInvestigational New Drugs
Volume29
Issue number2
DOIs
StatePublished - Apr 2011

Keywords

  • Doxorubicin
  • Motexafin gadolinium
  • Oxidation-reduction
  • Phase I
  • Ribonucleotide reductase

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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