TY - JOUR
T1 - Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases
AU - Carde, P.
AU - Timmerman, R.
AU - Mehta, M. P.
AU - Koprowski, C. D.
AU - Ford, J.
AU - Tishler, R. B.
AU - Miles, D.
AU - Miller, R. A.
AU - Renschler, M. F.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001/4/1
Y1 - 2001/4/1
N2 - Purpose: Motexafin gadolinium is a magnetic resonance imaging (MRI)-detectable redox active drug that localizes selectively in tumor cells and enhances the effect of radiation therapy. This phase lb/II trial of motexafin gadolinium, administered concurrently with 30 Gy in 10 fractions whole-brain radiation therapy (WBRT), was conducted to determine maximum-tolerated dose (MTD), dose-limiting toxicity, pharmacokinetics, and biolocalization in patients with brain metastases. Additional endpoints were radiologic response rate and survival. Patients and Methods: Motexafin gadolinium was administered before each radiation treatment in this open-label, multicenter, international trial. In phase lb, drug dose was escalated until the MTD was exceeded. In phase II, drug was evaluated in a narrow dose range. Results: In phase lb, the motexafin gadolinium dose was escalated in 39 patients (0.3 mg/kg to 8.4 mg/kg). In phase II, 22 patients received 5 mg/kg to 6.3 mg/kg motexafin gadolinium. Ten once-daily treatments were well tolerated. The MTD was 6.3 mg/kg, with dose-limiting reversible liver toxicity. Motexafin gadolinium's tumor selectivity was established using MRI. The radiologic response rate was 72% in phase II. Median survival was 4.7 months for all patients, 5.4 months for recursive partitioning analysis (RPA) class 2 patients, and 3.8 months for RPA class 3 patients. One-year actuarial survival for all patients was 25%. Conclusion: Motexafin gadolinium was well tolerated at doses up to 6.3 mg/kg, was selectively accumulated in tumors, and, when combined with WBRT of 30 Gy in 10 fractions, was associated with a high radiologic response rate.
AB - Purpose: Motexafin gadolinium is a magnetic resonance imaging (MRI)-detectable redox active drug that localizes selectively in tumor cells and enhances the effect of radiation therapy. This phase lb/II trial of motexafin gadolinium, administered concurrently with 30 Gy in 10 fractions whole-brain radiation therapy (WBRT), was conducted to determine maximum-tolerated dose (MTD), dose-limiting toxicity, pharmacokinetics, and biolocalization in patients with brain metastases. Additional endpoints were radiologic response rate and survival. Patients and Methods: Motexafin gadolinium was administered before each radiation treatment in this open-label, multicenter, international trial. In phase lb, drug dose was escalated until the MTD was exceeded. In phase II, drug was evaluated in a narrow dose range. Results: In phase lb, the motexafin gadolinium dose was escalated in 39 patients (0.3 mg/kg to 8.4 mg/kg). In phase II, 22 patients received 5 mg/kg to 6.3 mg/kg motexafin gadolinium. Ten once-daily treatments were well tolerated. The MTD was 6.3 mg/kg, with dose-limiting reversible liver toxicity. Motexafin gadolinium's tumor selectivity was established using MRI. The radiologic response rate was 72% in phase II. Median survival was 4.7 months for all patients, 5.4 months for recursive partitioning analysis (RPA) class 2 patients, and 3.8 months for RPA class 3 patients. One-year actuarial survival for all patients was 25%. Conclusion: Motexafin gadolinium was well tolerated at doses up to 6.3 mg/kg, was selectively accumulated in tumors, and, when combined with WBRT of 30 Gy in 10 fractions, was associated with a high radiologic response rate.
UR - http://www.scopus.com/inward/record.url?scp=0035300617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035300617&partnerID=8YFLogxK
U2 - 10.1200/JCO.2001.19.7.2074
DO - 10.1200/JCO.2001.19.7.2074
M3 - Article
C2 - 11283141
AN - SCOPUS:0035300617
SN - 0732-183X
VL - 19
SP - 2074
EP - 2083
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 7
ER -