Results of the Phase I Dose-Escalating Study of Motexafin Gadolinium With Standard Radiotherapy in Patients With Glioblastoma Multiforme

Judith M. Ford, Wendy Seiferheld, Jeffrey R. Alger, Genevieve Wu, Thyra J. Endicott, Minesh Mehta, Walter Curran, See Chun Phan

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Purpose: Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme. Methods and Materials: A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied. Results: The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94). Conclusion: The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide.

Original languageEnglish (US)
Pages (from-to)831-838
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume69
Issue number3
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

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Glioblastoma
gadolinium
radiation therapy
Radiotherapy
dosage
Survival
Maximum Tolerated Dose
temozolomide
Exanthema
toxicity
cancer
fever
motexafin gadolinium
Chills
Radiation Oncology
National Cancer Institute (U.S.)
Thumb
Program Evaluation
metastasis
Pruritus

Keywords

  • Glioblastoma multiforme
  • Glioma
  • Motexafin gadolinium
  • Radiation enhancer
  • Radiotherapy

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Results of the Phase I Dose-Escalating Study of Motexafin Gadolinium With Standard Radiotherapy in Patients With Glioblastoma Multiforme. / Ford, Judith M.; Seiferheld, Wendy; Alger, Jeffrey R.; Wu, Genevieve; Endicott, Thyra J.; Mehta, Minesh; Curran, Walter; Phan, See Chun.

In: International Journal of Radiation Oncology Biology Physics, Vol. 69, No. 3, 01.11.2007, p. 831-838.

Research output: Contribution to journalArticle

Ford, Judith M. ; Seiferheld, Wendy ; Alger, Jeffrey R. ; Wu, Genevieve ; Endicott, Thyra J. ; Mehta, Minesh ; Curran, Walter ; Phan, See Chun. / Results of the Phase I Dose-Escalating Study of Motexafin Gadolinium With Standard Radiotherapy in Patients With Glioblastoma Multiforme. In: International Journal of Radiation Oncology Biology Physics. 2007 ; Vol. 69, No. 3. pp. 831-838.
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abstract = "Purpose: Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme. Methods and Materials: A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied. Results: The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45{\%}), chills/fever (30{\%}), and self-limiting vesiculobullous rash of the thumb and fingers (42{\%}). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95{\%} confidence interval, 0.20-0.94). Conclusion: The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide.",
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