Investigational New Drugs

, Volume 29, Issue 2, pp 316–322 | Cite as

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
PHASE I STUDIES

Summary

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.

Keywords

Phase I Ribonucleotide reductase Motexafin gadolinium Oxidation-reduction Doxorubicin 

Notes

Acknowlegements

The authors acknowledge our patients, their families, and our clinic and research staff in the completion of this trial. The authors would like to thank Minesh P. Mehta, MBChB, for his thoughtful review of this manuscript. Melinda Baker assisted with preparation of this manuscript.

Financial and Grant Support

Pharmacyclics, Incorporated, Sunnyvale, CA

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Anne M. Traynor
    • 1
  • James P. Thomas
    • 1
    • 4
  • Ramesh K. Ramanathan
    • 2
    • 5
  • Tarak D. Mody
    • 3
  • Dona Alberti
    • 1
  • George Wilding
    • 1
  • Howard H. Bailey
    • 1
  1. 1.University of Wisconsin Paul P. Carbone Comprehensive Cancer CenterMadisonUSA
  2. 2.University of Pittsburgh Cancer InstitutePittsburghUSA
  3. 3.Pharmacyclics, Inc.SunnyvaleUSA
  4. 4.Ohio State University Comprehensive Cancer CenterColumbusUSA
  5. 5.Translational Genomics Research Clinical Research Services at Scottsdale Health CareScottsdaleUSA

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