Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme

Morris D. Groves, Vinay K. Puduvalli, Kenneth R. Hess, Kurt Jaeckle, Pamela Peterson, W. K.Alfred Yung, Victor A. Levin

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Abstract

Purpose: Novel therapies are needed for patients with recurrent glioblastoma multiforme (GBM). Because there is evidence that temozolomide (TMZ) has some activity in GBM and is well tolerated, and because of laboratory evidence that metalloproteinases are important in glioma cell invasion, the combination of TMZ and the matrix metalloproteinase inhibitor marimastat (MRM) in patients with recurrent GBM was studied. Patients and Methods: Forty-four patients with recurrent GBM after standard radiotherapy were enrolled. For 19 patients, this therapy was their first chemotherapy after tumor progression after irradiation; 25 others had received chemotherapy previously. TMZ 150 to 200 mg/m2 days 1 to 5 and MRM 50 mg days 8 to 28 was administered at 28-day intervals for two cycles; then patients were reevaluated. Treatment continued until progression of tumor or toxicity developed. Results: Joint and tendon pain was the major therapy-related toxicity and was reported in 47% of patients. Five patients (11%) were removed from the study because of intolerable joint pain. For all patients, the progression-free survival (PFS) at 6 months was 39%. Median PFS was 17 weeks, median overall survival was 45 weeks, and 12-month PFS was 16%. Conclusion: The combination of TMZ and MRM resulted in a PFS at 6 months that exceeded the literature target by 29%. This drug combination met phase II study criteria; further study in recurrent patients with GBM might be warranted. Further study of therapy-induced joint pain is necessary.

Original languageEnglish (US)
Pages (from-to)1383-1388
Number of pages6
JournalJournal of Clinical Oncology
Volume20
Issue number5
DOIs
StatePublished - Mar 1 2002

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temozolomide
Matrix Metalloproteinase Inhibitors
Glioblastoma
Disease-Free Survival
Arthralgia
marimastat
Therapeutics
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Groves, Morris D. ; Puduvalli, Vinay K. ; Hess, Kenneth R. ; Jaeckle, Kurt ; Peterson, Pamela ; Yung, W. K.Alfred ; Levin, Victor A. / Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme. In: Journal of Clinical Oncology. 2002 ; Vol. 20, No. 5. pp. 1383-1388.
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abstract = "Purpose: Novel therapies are needed for patients with recurrent glioblastoma multiforme (GBM). Because there is evidence that temozolomide (TMZ) has some activity in GBM and is well tolerated, and because of laboratory evidence that metalloproteinases are important in glioma cell invasion, the combination of TMZ and the matrix metalloproteinase inhibitor marimastat (MRM) in patients with recurrent GBM was studied. Patients and Methods: Forty-four patients with recurrent GBM after standard radiotherapy were enrolled. For 19 patients, this therapy was their first chemotherapy after tumor progression after irradiation; 25 others had received chemotherapy previously. TMZ 150 to 200 mg/m2 days 1 to 5 and MRM 50 mg days 8 to 28 was administered at 28-day intervals for two cycles; then patients were reevaluated. Treatment continued until progression of tumor or toxicity developed. Results: Joint and tendon pain was the major therapy-related toxicity and was reported in 47{\%} of patients. Five patients (11{\%}) were removed from the study because of intolerable joint pain. For all patients, the progression-free survival (PFS) at 6 months was 39{\%}. Median PFS was 17 weeks, median overall survival was 45 weeks, and 12-month PFS was 16{\%}. Conclusion: The combination of TMZ and MRM resulted in a PFS at 6 months that exceeded the literature target by 29{\%}. This drug combination met phase II study criteria; further study in recurrent patients with GBM might be warranted. Further study of therapy-induced joint pain is necessary.",
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Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme. / Groves, Morris D.; Puduvalli, Vinay K.; Hess, Kenneth R.; Jaeckle, Kurt; Peterson, Pamela; Yung, W. K.Alfred; Levin, Victor A.

In: Journal of Clinical Oncology, Vol. 20, No. 5, 01.03.2002, p. 1383-1388.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme

AU - Groves, Morris D.

AU - Puduvalli, Vinay K.

AU - Hess, Kenneth R.

AU - Jaeckle, Kurt

AU - Peterson, Pamela

AU - Yung, W. K.Alfred

AU - Levin, Victor A.

PY - 2002/3/1

Y1 - 2002/3/1

N2 - Purpose: Novel therapies are needed for patients with recurrent glioblastoma multiforme (GBM). Because there is evidence that temozolomide (TMZ) has some activity in GBM and is well tolerated, and because of laboratory evidence that metalloproteinases are important in glioma cell invasion, the combination of TMZ and the matrix metalloproteinase inhibitor marimastat (MRM) in patients with recurrent GBM was studied. Patients and Methods: Forty-four patients with recurrent GBM after standard radiotherapy were enrolled. For 19 patients, this therapy was their first chemotherapy after tumor progression after irradiation; 25 others had received chemotherapy previously. TMZ 150 to 200 mg/m2 days 1 to 5 and MRM 50 mg days 8 to 28 was administered at 28-day intervals for two cycles; then patients were reevaluated. Treatment continued until progression of tumor or toxicity developed. Results: Joint and tendon pain was the major therapy-related toxicity and was reported in 47% of patients. Five patients (11%) were removed from the study because of intolerable joint pain. For all patients, the progression-free survival (PFS) at 6 months was 39%. Median PFS was 17 weeks, median overall survival was 45 weeks, and 12-month PFS was 16%. Conclusion: The combination of TMZ and MRM resulted in a PFS at 6 months that exceeded the literature target by 29%. This drug combination met phase II study criteria; further study in recurrent patients with GBM might be warranted. Further study of therapy-induced joint pain is necessary.

AB - Purpose: Novel therapies are needed for patients with recurrent glioblastoma multiforme (GBM). Because there is evidence that temozolomide (TMZ) has some activity in GBM and is well tolerated, and because of laboratory evidence that metalloproteinases are important in glioma cell invasion, the combination of TMZ and the matrix metalloproteinase inhibitor marimastat (MRM) in patients with recurrent GBM was studied. Patients and Methods: Forty-four patients with recurrent GBM after standard radiotherapy were enrolled. For 19 patients, this therapy was their first chemotherapy after tumor progression after irradiation; 25 others had received chemotherapy previously. TMZ 150 to 200 mg/m2 days 1 to 5 and MRM 50 mg days 8 to 28 was administered at 28-day intervals for two cycles; then patients were reevaluated. Treatment continued until progression of tumor or toxicity developed. Results: Joint and tendon pain was the major therapy-related toxicity and was reported in 47% of patients. Five patients (11%) were removed from the study because of intolerable joint pain. For all patients, the progression-free survival (PFS) at 6 months was 39%. Median PFS was 17 weeks, median overall survival was 45 weeks, and 12-month PFS was 16%. Conclusion: The combination of TMZ and MRM resulted in a PFS at 6 months that exceeded the literature target by 29%. This drug combination met phase II study criteria; further study in recurrent patients with GBM might be warranted. Further study of therapy-induced joint pain is necessary.

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