Phase II Study of Imatinib Mesylate Plus Hydroxyurea in Adults With Recurrent Glioblastoma Multiforme Export

@article{citeulike:3680096, abstract = {PURPOSE: We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). RESULTS: Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27\% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9\%) achieved radiographic response, and 14 (42\%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16\%), thrombocytopenia (6\%), and edema (6\%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. CONCLUSION: Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM. 10.1200/JCO.2005.03.2185}, author = {Reardon, David A. and Egorin, Merrill J. and Quinn, Jennifer A. and Rich, Jeremy N. and Gururangan, Idharan and Vredenburgh, James J. and Desjardins, Annick and Sathornsumetee, Sith and Provenzale, James M. and Herndon, James E. and Dowell, Jeannette M. and Badruddoja, Michael A. and Mclendon, Roger E. and Lagattuta, Theodore F. and Kicielinski, Kimberly P. and Dresemann, Gregor and Sampson, John H. and Friedman, Allan H. and Salvado, August J. and Friedman, Henry S.}, citeulike-article-id = {3680096}, citeulike-linkout-0 = {http://dx.doi.org/10.1200/JCO.2005.03.2185}, citeulike-linkout-1 = {http://jco.ascopubs.org/cgi/content/abstract/23/36/9359}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16361636}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16361636}, day = {20}, doi = {10.1200/JCO.2005.03.2185}, journal = {J Clin Oncol}, keywords = {gbm, neuro}, month = {December}, number = {36}, pages = {9359--9368}, posted-at = {2008-11-24 00:32:39}, priority = {2}, title = {Phase II Study of Imatinib Mesylate Plus Hydroxyurea in Adults With Recurrent Glioblastoma Multiforme}, url = {http://dx.doi.org/10.1200/JCO.2005.03.2185}, volume = {23}, year = {2005} }

TY - JOUR ID - citeulike:3680096 L3 - citeulike-article-id:3680096 N2 - PURPOSE: We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). RESULTS: Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. CONCLUSION: Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM. 10.1200/JCO.2005.03.2185 IS - 36 JF - J Clin Oncol EP - 9368 TI - Phase II Study of Imatinib Mesylate Plus Hydroxyurea in Adults With Recurrent Glioblastoma Multiforme VL - 23 SP - 9359 KW - gbm KW - neuro AU - Reardon, David AU - Egorin, Merrill AU - Quinn, Jennifer AU - Rich, Jeremy AU - Gururangan, Idharan AU - Vredenburgh, James AU - Desjardins, Annick AU - Sathornsumetee, Sith AU - Provenzale, James AU - Herndon, James AU - Dowell, Jeannette AU - Badruddoja, Michael AU - Mclendon, Roger AU - Lagattuta, Theodore AU - Kicielinski, Kimberly AU - Dresemann, Gregor AU - Sampson, John AU - Friedman, Allan AU - Salvado, August AU - Friedman, Henry PY - 2005/12/20/ UR - http://dx.doi.org/10.1200/JCO.2005.03.2185 ER -