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.
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.
Authors: Minesh P Mehta; William R Shapiro; See C Phan; Radj Gervais; Christian Carrie; Pierre Chabot; Roy A Patchell; Michael J Glantz; Lawrence Recht; Corey Langer; Ranjan K Sur; Wilson H Roa; Marc A Mahe; Andre Fortin; Carsten Nieder; Christina A Meyers; Jennifer A Smith; Richard A Miller; Markus F Renschler Journal: Int J Radiat Oncol Biol Phys Date: 2008-10-30 Impact factor: 7.038
Authors: Darren Magda; Philip Lecane; Richard A Miller; Cheryl Lepp; Dale Miles; Mimi Mesfin; John E Biaglow; Vincent V Ho; Danny Chawannakul; Shailender Nagpal; Mazen W Karaman; Joseph G Hacia Journal: Cancer Res Date: 2005-05-01 Impact factor: 12.701
Authors: P Carde; R Timmerman; M P Mehta; C D Koprowski; J Ford; R B Tishler; D Miles; R A Miller; M F Renschler Journal: J Clin Oncol Date: 2001-04-01 Impact factor: 44.544
Authors: Andrew M Evens; Philip Lecane; Darren Magda; Sheila Prachand; Seema Singhal; Jeff Nelson; Richard A Miller; Ronald B Gartenhaus; Leo I Gordon Journal: Blood Date: 2004-09-23 Impact factor: 22.113
Authors: Minesh P Mehta; Patrick Rodrigus; C H J Terhaard; Aroor Rao; John Suh; Wilson Roa; Luis Souhami; Andrea Bezjak; Mark Leibenhaut; Ritsuko Komaki; Christopher Schultz; Robert Timmerman; Walter Curran; Jennifer Smith; See-Chun Phan; Richard A Miller; Markus F Renschler Journal: J Clin Oncol Date: 2003-07-01 Impact factor: 44.544