Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases

P. Carde, R. Timmerman, M. P. Mehta, C. D. Koprowski, J. Ford, R. B. Tishler, D. Miles, R. A. Miller, M. F. Renschler

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2074-2083
Number of pages10
JournalJournal of Clinical Oncology
Volume19
Issue number7
StatePublished - Apr 1 2001

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Radiation
Neoplasm Metastasis
Brain
Maximum Tolerated Dose
Radiotherapy
Magnetic Resonance Imaging
Pharmaceutical Preparations
Neoplasms
Survival
motexafin gadolinium
Multicenter Studies
Oxidation-Reduction
Survival Rate
Pharmacokinetics
Liver
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Carde, P., Timmerman, R., Mehta, M. P., Koprowski, C. D., Ford, J., Tishler, R. B., ... Renschler, M. F. (2001). Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases. Journal of Clinical Oncology, 19(7), 2074-2083.

Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases. / Carde, P.; Timmerman, R.; Mehta, M. P.; Koprowski, C. D.; Ford, J.; Tishler, R. B.; Miles, D.; Miller, R. A.; Renschler, M. F.

In: Journal of Clinical Oncology, Vol. 19, No. 7, 01.04.2001, p. 2074-2083.

Research output: Contribution to journalArticle

Carde, P, Timmerman, R, Mehta, MP, Koprowski, CD, Ford, J, Tishler, RB, Miles, D, Miller, RA & Renschler, MF 2001, 'Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases', Journal of Clinical Oncology, vol. 19, no. 7, pp. 2074-2083.
Carde, P. ; Timmerman, R. ; Mehta, M. P. ; Koprowski, C. D. ; Ford, J. ; Tishler, R. B. ; Miles, D. ; Miller, R. A. ; Renschler, M. F. / Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases. In: Journal of Clinical Oncology. 2001 ; Vol. 19, No. 7. pp. 2074-2083.
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title = "Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases",
abstract = "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.",
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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.

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.

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