FDA approves Temodar as treatment for glioblastoma multiforme

The FDA ( Food and Drug Administration ) has approved a new indication for Temozolomide ( Temodar ), an oral cytotoxic alkylating agent.

The drug, used concurrently with radiotherapy and as maintenance therapy after radiotherapy, can extend the lives of adult patients newly diagnosed with glioblastoma multiforme ( GBM ), the most common form of malignant brain cancer.

Glioblastoma multiforme is a rapidly growing neuroglia cell tumor of the central nervous system, most often located in the cerebrum.
It is the most common and deadliest type of primary brain tumor.
Glioblastoma multiforme is more common among males and occurs more frequently in Caucasians.
It is the third leading cause of cancer-related death in young adults age 20 to 29.
The median age at which people are diagnosed with glioblastoma multiforme is 50 to 60 years.
The annual incidence of GBM is four to five cases per 100,000 persons, with 8,000 to 10,000 new cases diagnosed per year in North America.

The new approval of Temozolomide for glioblastoma multiforme was based on efficacy and safety data from a large randomized controlled study conducted by the European Organization for Research and Treatment of Cancer ( EORTC ) in patients with newly diagnosed glioblastoma multiforme.

A total of 573 patients were randomized to treatment with radiation alone or to treatment with radiotherapy plus Temozolomide.

Median survival was improved by two and a half months in the Temozolomide group.
The median survival was 14.6 months with radiotherapy plus Temozolomide and 12.1 months with radiotherapy alone.

Concurrent with the approval for newly diagnosed glioblastoma multiforme, Temodar also received full approval for the treatment of adult patients with refractory anaplastic astrocytoma ( AA ), another form of brain tumor.
Temodar received accelerated approval for anaplastic astrocytoma in 1999.

Anaplastic astrocytoma is the second most common type of brain tumor and can progress to become glioblastoma multiforme.
It is a particularly aggressive tumor with few treatments available.
The median age at which people are diagnosed with anaplastic astrocytoma is 40 to 50 years.
The annual incidence of anaplastic astrocytoma is one to 1.5 cases per 100,000 persons, with 2,000 to 3,000 new cases diagnosed per year in North America.

Myelosuppression was the dose-limiting adverse event with Temozolomide.

The most common adverse events across the cumulative Temozolomide experience were alopecia, nausea, vomiting, anorexia, headache, and constipation.

Forty-nine percent of patients treated with Temozolomide reported one or more severe or life-threatening events, most commonly fatigue ( 13% ), convulsions ( 6% ), headache ( 5% ) and thrombocytopenia ( 5% ).

There may be a higher occurrence of opportunistic infections such as Pneumocystis carinii pneumonia ( PCP ) when Temozolomide is administered during a longer dosing regimen. However, all patients receiving Temozolomide, particularly patients receiving steroids, should be observed closely for the development of PCP regardless of the regimen.

Source: FDA, 2005