3364-Glioblastoma temozolomide chemoradiation followed by temozolomide OVERVIEW

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Treatment overview

This treatment regimen consists of two parts: 1 cycle (42 days) of temozolomide with concurrent radiation followed by 6 cycles of temozolomide alone.

Glioblastoma temozolomide chemoradiation (part 1)

Cycles:: 1 (42 days)

Patient information

Followed by:

Glioblastoma temozolomide following chemoradiation (part 2)

Frequency:: 28 days
Cycles:: 6 (consider continuing for up to 12 cycles at clinician discretion)

Patient information

Indications and patient population

Indication:

Newly diagnosed glioblastoma (WHO grade IV) with concurrent radiation therapy (60 Gy in 30 fractions over 6 weeks) (part 1 of protocol) followed by temozolomide alone (part 2 of protocol).

Caution:

Poor performance status
Elderly patients not suitable for this regimen should be considered for the short course regimen (Link to overview of the short course regimen in elderly patients)

Evidence

The evidence supporting this treatment comes from a multicentre, randomised, phase 3 trial in patients with newly diagnosed histologically confirmed grade 4 glioblastoma. 573 patients aged between 18 and 70 years, WHO PS of 2 or less were randomised to either standard RT (60 Gy in 30 daily fractions of 2 Gy) or the same RT and concomitant temozolomide (TMZ 75 mg/m²/day, daily up to 49 days) followed by up to 6 cycles of adjuvant TMZ (150 to 200 mg/m² daily on days 1 to 5 every 28 days). The primary end point was overall survival. Secondary end points were progression free survival, safety, and quality of life.^r ^r

Efficacy

After a median follow up of 5 years, the overall survival was 27.2% at 2 years, 16.0% at 3 years, 12.1% at 4 years and 9.8% at 5 years with temozolomide, versus 10.9%, 4.4%, 3.0% and 1.9% with radiation therapy alone (HR= 0.6, 95% CI 0.5 -0.7; p < 0.0001). A benefit of combined therapy was recorded in all clinical prognostics groups, including patients aged 60-70 years.^r

Overall and progression-free survival according to treatment group*

Kaplan-Meier estimates of overall survival according to treatment group

Toxicity

Only 8% of patients discontinued adjuvant TMZ because of toxic effects. Beginning with cycle 2 the dose of TMZ was increased to 200 mg/m²in 67% of patients. Only 9% of patients did not receive the higher dose because of haematological toxicity. Severe myelosuppression was observed in 16% of patients, leading to the early discontinuation of chemotherapy in 5% of patients.^r

Haematologic toxicity ^r Grade 3/4	Concomitant TMZ/RT n=284 (%)	Adjuvant TMZ n=223 (%)	Entire study period* n=284 (%)
Leucopenia	2	5	7
Neutropenia	4	4	7
Thrombocytopenia	3	11	12
Anaemia	less than 1	1	1
Any	7	14	16

* Entire study period was defined as the period from study entry to seven days after disease progression

References References

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Read abstract

[%abstract%]
: Stupp, R., M. Gander, S. Leyvraz, et al. 2001. "Current and future developments in the use of temozolomide for the treatment of brain tumours." Lancet Oncol 2(9):552-560.

Read abstract

Abstract Brain tumours comprise only 2% of all adult cancers, but they are among the most debilitating malignant diseases. Temozolomide, an alkylating agent that can be administered orally, has been approved for the treatment of recurrent malignant glioma on a daily schedule for 5-day cycles. Continuous administration schedules with a higher dose intensity are being explored, but an improvement in efficiency remains to be shown. The benefit from temozolomide given as a single agent in recurrent disease will be several weeks at best. This drug is therefore now undergoing clinical testing as neoadjuvant chemotherapy or with concomitant radiotherapy in patients with newly diagnosed glioma. Several phase I trials are investigating the combination of temozolomide with other agents active against brain tumours. This review briefly summarises the pharmacological background and clinical development of temozolomide and focuses on current and future clinical exploration of this drug for the treatment of brain tumours
: Stupp, R., P. Y. Dietrich, Kraljevic S. Ostermann, et al. 2002. "Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide." J.Clin Oncol 20(5):1375-1382.

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Abstract Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM. PATIENTS AND METHODS: Sixty-four patients were enrolled onto this open-label, phase II trial. Temozolomide (75 mg/m(2)/d x 7 d/wk for 6 weeks) was administered orally concomitant with fractionated radiotherapy (60 Gy total dose: 2 Gy x 5 d/wk for 6 weeks) followed by temozolomide monotherapy (200 mg/m(2)/d x 5 days, every 28 days for six cycles). The primary end points were safety and tolerability, and the secondary end point was overall survival. RESULTS: Concomitant radiation plus temozolomide therapy was safe and well tolerated. Nonhematologic toxicities were rare and mild to moderate in severity. During the concomitant treatment phase, grade 3 or 4 neutropenia, thrombocytopenia, or both were observed in 6% of patients, including two severe infections with Pneumocystis carinii. During adjuvant temozolomide, 2% and 6% of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia, respectively. Median survival was 16 months, and the 1- and 2-year survival rates were 58% and 31%, respectively. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome. CONCLUSION: Continuous daily temozolomide and concomitant radiation is safe. This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma. Further investigation is warranted, and a randomized trial is ongoing

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History

Version 2

Date	Summary of changes
27/02/2025	Protocol status updated to review as required to align with protocol parts ID 365 and ID 366. Flag added, review date removed and version number increased to V.2. Read more about as required review protocol status in this factsheet.

Version 1

Date	Summary of changes
19/03/2018	Overview page created to highlight the two parts of the protocol: ID 365 and ID 366. Approved and published on eviQ
21/09/2022	Protocol reviewed electronically by Medical Oncology Reference Committee. No changes. Next review in 5 years.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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First approved:: 19 March 2018
Last reviewed:: 21 September 2022
Review due:: As required

The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/3364

01 Apr 2025

Glioblastoma temozolomide chemoradiation followed by temozolomide OVERVIEW