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Topic: Brain tumor cell invasion and metastasis: anatomical,
biological and clinical considerations

Gemcitabine followed by radiotherapy in treatment of newly diagnosed
high-grade gliomas

Maha El-Naggar , Mervat Omar , Ahmed Elgeriany , Godefridus J. Peters , Amina Mostafa , Samir Shehata 1
2
1,3
1
3
1
1 Department of Medical oncology, Assiut University Hospital, Assiut 71515, Egypt.
2 Department of Neurosurgery, Assiut University Hospital, Assiut 71515, Egypt.
3 Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands.
Correspondence to: Dr. Maha El-Naggar, Department of Medical oncology, Assiut University Hospital, Assiut 71515, Egypt. E-mail: maha_elnaggar@yahoo.com
A B S T R AC T
Aim: High-grade glioblastoma multiforme (GBM) has a poor median overall survival (OS). The standard treatment after surgery
is temozolomide and radiotherapy (RTH). Patients with unmethylated methylguanine-methyltransferase promoter (MGMT) have
no or little benefit from temozolomide and are eligible for alternative therapies. Gemcitabine is a good radiosensitizer. We aimed
to evaluate the combination of gemcitabine with RTH in newly diagnosed GBM. Methods: The study was a prospective phase II
study. Eligible patients were required to have histologically proven anaplastic astrocytoma or GBM. Patients underwent biopsies or
subtotal resection. The treatment consisted of fixed-dose rate gemcitabine 175 mg/m weekly followed after 24 h by standard cranial
2
RTH for 6 weeks. Tumor response was evaluated by Macdonald criteria. In case of progression, patients received temozolomide
(200 mg/m /5 days every 28 days). Results: Thirty patients with a median age of 52 years (30-69), 73%/27% male/female, the
2
Eastern Cooperative Oncology Group performance status 1 (range 0-2) were enrolled. Five patients had a partial-response (17%)
and 13 stable-disease (43%). Median time to progression was 7.88 months (95% CI 6.1-9.69) and OS was 11.77 months (95% CI
9.97-13.56). The treatment was well tolerated with grade-3 neutropenia in 3, grade-3 anemia in 2 and impaired liver enzymes
in 1 patient. Conclusion: Gemcitabine followed by radiotherapy is active and promising regimen in newly diagnosed GBM.
Gemcitabine uptake is easy, with a long local retention of active metabolites, precluding systemic side effects of radiosensitization.
In a phase III study this treatment should be evaluated in patients with unmethylated MGMT promoter who will not benefit from
temozolomide.

Key words: Gemcitabine; radiation; glioblastoma multiforma; temozolomide

INTRODUCTION dose of 60 Gray (Gy) significantly prolongs survival. There
have been many efforts to intensify radiotherapy, including
Malignant gliomas grade 3 anaplastic astrocytoma (AA) the use of radiosenstizers, brachytherapy, radioactive seeds
or grade 4 glioblastoma multiforme (GBM) are rapidly implanted in the tumor bed, and stereotactic radiosurgery in
progressing primary brain tumors, which in spite of selected cases. [4]
advances in surgery, radiotherapy and chemotherapy, remain
associated with high morbidity and mortality. Despite the Initially the routine use of chemotherapy in addition to
[1]
current multimodality therapy, the overall median survival cranial irradiation was controversial. Individual randomized,
for newly diagnosed patients is 10 months for patients with controlled studies demonstrated no significant improvement
GBM and 2-3 years for those with AA. [2,3] in median survival with single agent or multiple agents
chemotherapy, although a significant increase in survival
Standard treatment of malignant gliomas is surgery, was noted in a meta-analysis. There was a significant
[1]
followed by radiotherapy concomitant with temozolomide
(TMZ), followed by adjuvant TMZ (Stupp et al., 2005). This is an open access article distributed under the terms of the Creative
[2]
Surgery followed by involved field radiotherapy up to total Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
the author is credited and the new creations are licensed under the identical
Access this article online terms.
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How to cite this article: El-Naggar M, Omar M, Elgeriany A, Peters
GJ, Mostafa A, Shehata S. Gemcitabine followed by radiotherapy in
treatment of newly diagnosed high-grade gliomas. J Cancer Metasta
DOI: Treat 2016;2:188-94.
10.20517/2394-4722.2016.15
Received: 05-04-2016; Accepted: 09-05-2016.

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©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc.