Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma: A phase II cytokine working group study

Michael B. Atkins, Jeffrey A. Sosman, Sanjiv Agarwala, Theodore Logan, Joseph I. Clark, Marc S. Ernstoff, David Lawson, Janice P. Dutcher, Geoffrey Weiss, Brendan Curti, Kim A. Margolin

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Abstract

BACKGROUND. The combination of temozolomide (TMZ) and thalidomide was reported to produce a high response rate, including shrinkage of brain metastases, in patients with metastatic melanoma. The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma. METHODS. Patients with melanoma, CNS metastases documented by magnetic resonance imaging, and no prior systemic chemotherapy received WBRT, 30 Gray in 10 fractions, Days 1 to 5 and 8 to 12; TMZ, 75 mg/m2/day, Weeks 1 to 6; and thalidomide, 100 mg/day, Weeks 1 to 4, then escalated by 100 mg/day at Weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at Week 10. Patients without CNS or clinically significant systemic disease progression received additional cycles of TMZ at 10-week intervals. RESULTS. Thirty-nine patients received treatment, and 3 exhibited CNS response (1 complete response, 2 partial responses) (response rate, 7.6%; 95% confidence interval, 0.7%-16.1%), all unconfirmed by repeat imaging. Seven patients had stable CNS disease at 10 weeks. No patient exhibited a systemic response. Only 4 patients received 2 cycles of therapy, and just 1 received 3. Median time to progression was 7 weeks, and median overall survival was 4 months. Grade 3-4 side effects included deep venous thrombosis (3), pulmonary embolism (1), and CNS events (12). Eighteen (45%) patients required admission for side effects (7) and/or symptomatic disease progression (11). CONCLUSIONS. The efficacy of TMZ, thalidomide, and WBRT in the treatment of CNS metastatic melanoma is low. Other treatment approaches should be considered for this patient population.

Original languageEnglish
Pages (from-to)2139-2145
Number of pages7
JournalCancer
Volume113
Issue number8
DOIs
StatePublished - Oct 15 2008

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temozolomide
Thalidomide
Melanoma
Radiotherapy
Cytokines
Neoplasm Metastasis
Brain
Disease Progression
Patient Admission
Central Nervous System Diseases
Therapeutics

Keywords

  • Brain metastases
  • Melanoma
  • Radiation therapy
  • Temozolomide
  • Thalidomide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma : A phase II cytokine working group study. / Atkins, Michael B.; Sosman, Jeffrey A.; Agarwala, Sanjiv; Logan, Theodore; Clark, Joseph I.; Ernstoff, Marc S.; Lawson, David; Dutcher, Janice P.; Weiss, Geoffrey; Curti, Brendan; Margolin, Kim A.

In: Cancer, Vol. 113, No. 8, 15.10.2008, p. 2139-2145.

Research output: Contribution to journalArticle

Atkins, MB, Sosman, JA, Agarwala, S, Logan, T, Clark, JI, Ernstoff, MS, Lawson, D, Dutcher, JP, Weiss, G, Curti, B & Margolin, KA 2008, 'Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma: A phase II cytokine working group study', Cancer, vol. 113, no. 8, pp. 2139-2145. https://doi.org/10.1002/cncr.23805
Atkins, Michael B. ; Sosman, Jeffrey A. ; Agarwala, Sanjiv ; Logan, Theodore ; Clark, Joseph I. ; Ernstoff, Marc S. ; Lawson, David ; Dutcher, Janice P. ; Weiss, Geoffrey ; Curti, Brendan ; Margolin, Kim A. / Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma : A phase II cytokine working group study. In: Cancer. 2008 ; Vol. 113, No. 8. pp. 2139-2145.
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title = "Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma: A phase II cytokine working group study",
abstract = "BACKGROUND. The combination of temozolomide (TMZ) and thalidomide was reported to produce a high response rate, including shrinkage of brain metastases, in patients with metastatic melanoma. The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma. METHODS. Patients with melanoma, CNS metastases documented by magnetic resonance imaging, and no prior systemic chemotherapy received WBRT, 30 Gray in 10 fractions, Days 1 to 5 and 8 to 12; TMZ, 75 mg/m2/day, Weeks 1 to 6; and thalidomide, 100 mg/day, Weeks 1 to 4, then escalated by 100 mg/day at Weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at Week 10. Patients without CNS or clinically significant systemic disease progression received additional cycles of TMZ at 10-week intervals. RESULTS. Thirty-nine patients received treatment, and 3 exhibited CNS response (1 complete response, 2 partial responses) (response rate, 7.6{\%}; 95{\%} confidence interval, 0.7{\%}-16.1{\%}), all unconfirmed by repeat imaging. Seven patients had stable CNS disease at 10 weeks. No patient exhibited a systemic response. Only 4 patients received 2 cycles of therapy, and just 1 received 3. Median time to progression was 7 weeks, and median overall survival was 4 months. Grade 3-4 side effects included deep venous thrombosis (3), pulmonary embolism (1), and CNS events (12). Eighteen (45{\%}) patients required admission for side effects (7) and/or symptomatic disease progression (11). CONCLUSIONS. The efficacy of TMZ, thalidomide, and WBRT in the treatment of CNS metastatic melanoma is low. Other treatment approaches should be considered for this patient population.",
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author = "Atkins, {Michael B.} and Sosman, {Jeffrey A.} and Sanjiv Agarwala and Theodore Logan and Clark, {Joseph I.} and Ernstoff, {Marc S.} and David Lawson and Dutcher, {Janice P.} and Geoffrey Weiss and Brendan Curti and Margolin, {Kim A.}",
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T1 - Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma

T2 - A phase II cytokine working group study

AU - Atkins, Michael B.

AU - Sosman, Jeffrey A.

AU - Agarwala, Sanjiv

AU - Logan, Theodore

AU - Clark, Joseph I.

AU - Ernstoff, Marc S.

AU - Lawson, David

AU - Dutcher, Janice P.

AU - Weiss, Geoffrey

AU - Curti, Brendan

AU - Margolin, Kim A.

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N2 - BACKGROUND. The combination of temozolomide (TMZ) and thalidomide was reported to produce a high response rate, including shrinkage of brain metastases, in patients with metastatic melanoma. The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma. METHODS. Patients with melanoma, CNS metastases documented by magnetic resonance imaging, and no prior systemic chemotherapy received WBRT, 30 Gray in 10 fractions, Days 1 to 5 and 8 to 12; TMZ, 75 mg/m2/day, Weeks 1 to 6; and thalidomide, 100 mg/day, Weeks 1 to 4, then escalated by 100 mg/day at Weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at Week 10. Patients without CNS or clinically significant systemic disease progression received additional cycles of TMZ at 10-week intervals. RESULTS. Thirty-nine patients received treatment, and 3 exhibited CNS response (1 complete response, 2 partial responses) (response rate, 7.6%; 95% confidence interval, 0.7%-16.1%), all unconfirmed by repeat imaging. Seven patients had stable CNS disease at 10 weeks. No patient exhibited a systemic response. Only 4 patients received 2 cycles of therapy, and just 1 received 3. Median time to progression was 7 weeks, and median overall survival was 4 months. Grade 3-4 side effects included deep venous thrombosis (3), pulmonary embolism (1), and CNS events (12). Eighteen (45%) patients required admission for side effects (7) and/or symptomatic disease progression (11). CONCLUSIONS. The efficacy of TMZ, thalidomide, and WBRT in the treatment of CNS metastatic melanoma is low. Other treatment approaches should be considered for this patient population.

AB - BACKGROUND. The combination of temozolomide (TMZ) and thalidomide was reported to produce a high response rate, including shrinkage of brain metastases, in patients with metastatic melanoma. The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma. METHODS. Patients with melanoma, CNS metastases documented by magnetic resonance imaging, and no prior systemic chemotherapy received WBRT, 30 Gray in 10 fractions, Days 1 to 5 and 8 to 12; TMZ, 75 mg/m2/day, Weeks 1 to 6; and thalidomide, 100 mg/day, Weeks 1 to 4, then escalated by 100 mg/day at Weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at Week 10. Patients without CNS or clinically significant systemic disease progression received additional cycles of TMZ at 10-week intervals. RESULTS. Thirty-nine patients received treatment, and 3 exhibited CNS response (1 complete response, 2 partial responses) (response rate, 7.6%; 95% confidence interval, 0.7%-16.1%), all unconfirmed by repeat imaging. Seven patients had stable CNS disease at 10 weeks. No patient exhibited a systemic response. Only 4 patients received 2 cycles of therapy, and just 1 received 3. Median time to progression was 7 weeks, and median overall survival was 4 months. Grade 3-4 side effects included deep venous thrombosis (3), pulmonary embolism (1), and CNS events (12). Eighteen (45%) patients required admission for side effects (7) and/or symptomatic disease progression (11). CONCLUSIONS. The efficacy of TMZ, thalidomide, and WBRT in the treatment of CNS metastatic melanoma is low. Other treatment approaches should be considered for this patient population.

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