Faculty Collaboration Database

Phase I trial of motexafin gadolinium and doxorubicin in the treatment of advanced malignancies. Invest New Drugs 2011 Apr;29(2):316-22

Date

12/10/2009

Pubmed ID

19997959

Pubmed Central ID

PMC3038176

DOI

10.1007/s10637-009-9364-z

Scopus ID

2-s2.0-79957532438 (requires institutional sign-in at Scopus site)   4 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.

Author List

Traynor AM, Thomas JP, Ramanathan RK, Mody TD, Alberti D, Wilding G, Bailey HH

Author

James P. Thomas MD, PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Demography
Dose-Response Relationship, Drug
Doxorubicin
Female
Humans
Male
Metalloporphyrins
Middle Aged
Neoplasms
Treatment Outcome