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Clinical Trial
. 2010 Mar;12(3):289-96.
doi: 10.1093/neuonc/nop030. Epub 2010 Jan 11.

Phase II trial of low-dose continuous (metronomic) treatment of temozolomide for recurrent glioblastoma

Doo-Sik Kong  1 , Jung-Il Lee, Jong Hyun Kim, Sung Tae Kim, Won Seog Kim, Yeon-Lim Suh, Seung Myung Dong, Do-Hyun Nam
Affiliations
Clinical Trial

Phase II trial of low-dose continuous (metronomic) treatment of temozolomide for recurrent glioblastoma

Doo-Sik Kong et al. Neuro Oncol. 2010 Mar.

Abstract

The prognosis for patients with recurrent glioblastomas (GBMs) is dismal, with a median survival of 3-6 months. We performed a phase II trial of low-dose continuous (metronomic) treatment using temozolomide (TMZ) for recurrent GBMs. TMZ-refractory patients with GBM who experienced disease recurrence or progression during or after the cyclic treatment schedule of TMZ after surgery and standard radiotherapy were eligible. This phase II trial included 2 cohorts of patients. The initial cohort, comprising 10 patients, received TMZ at 40 mg/m(2) everyday. After this regimen seemed safe and effective, the metronomic schedule was changed to 50 mg/m(2) everyday. The second cohort, comprising 28 patients, received TMZ at 50 mg/m(2) everyday. The 6-month progression-free survival in all 38 patients was 32.5% (95% CI: 29.3%-35.8%) and the 6-month overall survival was 56.0% (95% CI: 36.2%-75.8%). One patient developed a grade III neutropenia, grade II thrombocytopenia in 3 patients, and grade II increase of liver enzyme (GOT/GPT) in 3 patients. Of all patients included in this study, 4 patients were withdrawn from this study because of side effects including sustained hematological disorders, cryptococcal infection, and cellulitis. In a response group, quality of life measured with short form-36 was well preserved, when compared with the pretreatment status. Metronomic treatment of TMZ is an effective treatment for recurrent GBM that is even refractory to conventional treatment of TMZ and has acceptable toxicity.

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Figures

Fig. 1.
Fig. 1.
Left, before treatment. On the gadolinium-enhanced T1-weighted magnetic resonance scans, the enhancing lesion on the left frontal lobe shows increased cerebral blood perfusion (arrows). Right, after follow-up MRI 8 months after treatment. The size of the enhancing lesion on contrast T1-weighted image was not definitely changed and cerebral blood perfusion (arrows) was partially reduced.
Fig. 2.
Fig. 2.
This 48-year-old woman underwent metronomic treatment after tumor recurrence. Left; before treatment; right, after follow-up MRI 4 months after treatment.
Fig. 3.
Fig. 3.
Kaplan–Meier PFS.
Fig. 4.
Fig. 4.
Kaplan–Meier OS from the recurrence.
Fig. 5.
Fig. 5.
Assessment of QOL using SF-36 of all patients (upper) in this study and good responders among them (lower).
See this image and copyright information in PMC

References

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