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

Journal Article · Thu Nov 01 04:00:00 EDT 2007 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2007.04.017· OSTI ID:21039589

Seiferheld, Wendy ^[1]; Alger, Jeffrey R; Wu, Genevieve ^[2]; Endicott, Thyra J ^[3]; Mehta, Minesh ^[4]; Curran, Walter ^[5]; Phan, See-Chun ^[6]

---

1. Radiation Therapy Oncology Group Statistical Unit, Philadelphia, PA (United States)
2. Department of Radiology, University of California, Los Angeles, School of Medicine, Los Angeles, CA (United States)
3. Department of Radiation Oncology, Torrance Memorial Medical Center, Torrance, CA (United States)
4. Department of Radiation Oncology, University of Wisconsin School of Medicine, Madison, WI (United States)
5. Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, PA (United States)
6. Pharmacyclics Inc., Sunnyvale, CA (United States)

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.

• OSTI ID: 21039589
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 69; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
AMINOTRANSFERASES
BRAIN
EVALUATION
FEVER
FINGERS
GADOLINIUM
GLIOMAS
HEALTH HAZARDS
METASTASES
PATIENTS
RADIATION DOSES
RADIOTHERAPY
TOXICITY