Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma

A North American Brain Tumor Consortium Study

Kurt Jaeckle, Kenneth R. Hess, W. K.Alfred Yung, Harry Greenberg, Howard Fine, David Schiff, Ian F. Pollack, John Kuhn, Karen Fink, Minesh Mehta, Timothy Cloughesy, M. Kelly Nicholas, Susan Chang, Michael Prados

Research output: Contribution to journalArticle

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Abstract

Purpose: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG. Patients and Methods: Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m2/d, days 1 through 5, and cRA 100 mg/m2/d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12. Results: Eighty-eight eligible patients (glioblastoma multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43% (95% confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%). Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to 57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable patients, there were two (3%) complete responses and eight (12%) partial responses (complete plus partial response, 15%). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenia (1.8%), thrombocytopenia (1.4%), and hypertriglyceridemia (1.2%). Conclusion: TMZ and cRA were active, exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our previously reported database (glioblastoma multiforme: expected, 30%; observed, 32%; anaplastic glioma: expected, 40%; observed, 50%).

Original languageEnglish (US)
Pages (from-to)2305-2311
Number of pages7
JournalJournal of Clinical Oncology
Volume21
Issue number12
DOIs
StatePublished - Jun 15 2003

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temozolomide
Isotretinoin
NSC 153174
Brain Neoplasms
Glioma
Confidence Intervals
Tretinoin
Disease-Free Survival
Glioblastoma
Survival
Therapeutics
Oligodendroglioma
Agranulocytosis
Hypertriglyceridemia
Astrocytoma
Thrombocytopenia
Databases
Radiation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jaeckle, Kurt ; Hess, Kenneth R. ; Yung, W. K.Alfred ; Greenberg, Harry ; Fine, Howard ; Schiff, David ; Pollack, Ian F. ; Kuhn, John ; Fink, Karen ; Mehta, Minesh ; Cloughesy, Timothy ; Nicholas, M. Kelly ; Chang, Susan ; Prados, Michael. / Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma : A North American Brain Tumor Consortium Study. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 12. pp. 2305-2311.
@article{469c46ce18454ed18a6e06b96700e503,
title = "Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: A North American Brain Tumor Consortium Study",
abstract = "Purpose: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG. Patients and Methods: Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m2/d, days 1 through 5, and cRA 100 mg/m2/d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12. Results: Eighty-eight eligible patients (glioblastoma multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43{\%} (95{\%} confidence interval [CI], 33{\%} to 54{\%}) and PFS12 was 16{\%} (95{\%} CI, 10{\%} to 26{\%}). Median overall PFS was 19 weeks (95{\%} CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95{\%} CI, 36 to 58 weeks). OS was 46{\%} (95{\%} CI, 36{\%} to 57{\%}) at 52 weeks and 21{\%} (95{\%} CI, 13{\%} to 31{\%}) at 104 weeks. Of 84 assessable patients, there were two (3{\%}) complete responses and eight (12{\%}) partial responses (complete plus partial response, 15{\%}). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenia (1.8{\%}), thrombocytopenia (1.4{\%}), and hypertriglyceridemia (1.2{\%}). Conclusion: TMZ and cRA were active, exceeding our 20{\%} thresholds for PFS 6 success, assuming 20{\%} improvement over our previously reported database (glioblastoma multiforme: expected, 30{\%}; observed, 32{\%}; anaplastic glioma: expected, 40{\%}; observed, 50{\%}).",
author = "Kurt Jaeckle and Hess, {Kenneth R.} and Yung, {W. K.Alfred} and Harry Greenberg and Howard Fine and David Schiff and Pollack, {Ian F.} and John Kuhn and Karen Fink and Minesh Mehta and Timothy Cloughesy and Nicholas, {M. Kelly} and Susan Chang and Michael Prados",
year = "2003",
month = "6",
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doi = "10.1200/JCO.2003.12.097",
language = "English (US)",
volume = "21",
pages = "2305--2311",
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Jaeckle, K, Hess, KR, Yung, WKA, Greenberg, H, Fine, H, Schiff, D, Pollack, IF, Kuhn, J, Fink, K, Mehta, M, Cloughesy, T, Nicholas, MK, Chang, S & Prados, M 2003, 'Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: A North American Brain Tumor Consortium Study', Journal of Clinical Oncology, vol. 21, no. 12, pp. 2305-2311. https://doi.org/10.1200/JCO.2003.12.097

Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma : A North American Brain Tumor Consortium Study. / Jaeckle, Kurt; Hess, Kenneth R.; Yung, W. K.Alfred; Greenberg, Harry; Fine, Howard; Schiff, David; Pollack, Ian F.; Kuhn, John; Fink, Karen; Mehta, Minesh; Cloughesy, Timothy; Nicholas, M. Kelly; Chang, Susan; Prados, Michael.

In: Journal of Clinical Oncology, Vol. 21, No. 12, 15.06.2003, p. 2305-2311.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma

T2 - A North American Brain Tumor Consortium Study

AU - Jaeckle, Kurt

AU - Hess, Kenneth R.

AU - Yung, W. K.Alfred

AU - Greenberg, Harry

AU - Fine, Howard

AU - Schiff, David

AU - Pollack, Ian F.

AU - Kuhn, John

AU - Fink, Karen

AU - Mehta, Minesh

AU - Cloughesy, Timothy

AU - Nicholas, M. Kelly

AU - Chang, Susan

AU - Prados, Michael

PY - 2003/6/15

Y1 - 2003/6/15

N2 - Purpose: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG. Patients and Methods: Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m2/d, days 1 through 5, and cRA 100 mg/m2/d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12. Results: Eighty-eight eligible patients (glioblastoma multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43% (95% confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%). Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to 57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable patients, there were two (3%) complete responses and eight (12%) partial responses (complete plus partial response, 15%). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenia (1.8%), thrombocytopenia (1.4%), and hypertriglyceridemia (1.2%). Conclusion: TMZ and cRA were active, exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our previously reported database (glioblastoma multiforme: expected, 30%; observed, 32%; anaplastic glioma: expected, 40%; observed, 50%).

AB - Purpose: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG. Patients and Methods: Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m2/d, days 1 through 5, and cRA 100 mg/m2/d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12. Results: Eighty-eight eligible patients (glioblastoma multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43% (95% confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%). Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to 57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable patients, there were two (3%) complete responses and eight (12%) partial responses (complete plus partial response, 15%). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenia (1.8%), thrombocytopenia (1.4%), and hypertriglyceridemia (1.2%). Conclusion: TMZ and cRA were active, exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our previously reported database (glioblastoma multiforme: expected, 30%; observed, 32%; anaplastic glioma: expected, 40%; observed, 50%).

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