Procarbazine and CCNU chemotherapy for recurrent glioblastoma with MGMT promoter methylation

Se Hyuk Kim, Heon Yoo, Jong Hee Chang, Chae Yong Kim, Dong Sup Chung, Se Hoon Kim, Sung Hae Park, Youn Soo Lee, Seung Ho Yang

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Abstract

Background: While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. Methods: Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m2) on day 1 and procarbazine (60 mg/m2) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6). Results: One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. Conclusion: The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

Original languageEnglish
Article numbere167
JournalJournal of Korean medical science
Volume33
Issue number24
DOIs
Publication statusPublished - 2018 Jan 1

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Lomustine
Procarbazine
Methyltransferases
Glioblastoma
Methylation
Drug Therapy
DNA
temozolomide
Vincristine
Disease-Free Survival
Survival
Chemoradiotherapy
Glioma
Registries
Therapeutics
Survival Rate
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Kim, Se Hyuk ; Yoo, Heon ; Chang, Jong Hee ; Kim, Chae Yong ; Chung, Dong Sup ; Kim, Se Hoon ; Park, Sung Hae ; Lee, Youn Soo ; Yang, Seung Ho. / Procarbazine and CCNU chemotherapy for recurrent glioblastoma with MGMT promoter methylation. In: Journal of Korean medical science. 2018 ; Vol. 33, No. 24.
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title = "Procarbazine and CCNU chemotherapy for recurrent glioblastoma with MGMT promoter methylation",
abstract = "Background: While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. Methods: Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m2) on day 1 and procarbazine (60 mg/m2) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6). Results: One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25{\%} and 12.5{\%} at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95{\%} confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. Conclusion: The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.",
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Procarbazine and CCNU chemotherapy for recurrent glioblastoma with MGMT promoter methylation. / Kim, Se Hyuk; Yoo, Heon; Chang, Jong Hee; Kim, Chae Yong; Chung, Dong Sup; Kim, Se Hoon; Park, Sung Hae; Lee, Youn Soo; Yang, Seung Ho.

In: Journal of Korean medical science, Vol. 33, No. 24, e167, 01.01.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Procarbazine and CCNU chemotherapy for recurrent glioblastoma with MGMT promoter methylation

AU - Kim, Se Hyuk

AU - Yoo, Heon

AU - Chang, Jong Hee

AU - Kim, Chae Yong

AU - Chung, Dong Sup

AU - Kim, Se Hoon

AU - Park, Sung Hae

AU - Lee, Youn Soo

AU - Yang, Seung Ho

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. Methods: Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m2) on day 1 and procarbazine (60 mg/m2) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6). Results: One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. Conclusion: The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

AB - Background: While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. Methods: Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m2) on day 1 and procarbazine (60 mg/m2) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6). Results: One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. Conclusion: The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

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