THERAPEUTICS

Brands

• Temodar, Temodal, Temcad, Methazolastone

Generic?

• No

Class

• Antineoplastic agent

Commonly Prescribed for

(FDA approved in bold)

• Refractory anaplastic astrocytoma

• Newly diagnosed glioblastoma multiforme (GBM) combined with radiotherapy

• Malignant prolactinoma

• Oligodendroglioma

• Primary CNS lymphoma

• Melanoma

How the Drug Works

• An alkylating agent prodrug whose clinical actions are due to metabolite methyl triazeno imidazole carboxamide (MTIC). The metabolites methylate DNA guanine bases, resulting in apoptosis of tumor cells. Treatment success is more likely in tumors with silencing of the O-6-methylguanine- DNA methyltransferase (MGMT) gene, which is important in demethylation

How Long Until It Works

• Used to prolong survival. Clinical benefits may be difficult to determine for weeks to months

If It Works

• May be continued for up to 6 cycles

If It Doesn't Work

• Discontinue treatment, consider alternative salvage chemotherapy such as bevacizumab or dexamethasone depending on clinical situation

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Most patients will receive co-treatment with radiotherapy

• One small study shows potential benefit when combined with chloroquine. Another with the topoisomerase-1 inhibitor irinotecan

• O-6-Benzylguanine may be useful in those with treatment-resistant anaplastic glioma, but does not appear to be effective against GBM

Tests

• CBC before and during treatments, especially in elderly patients

• Chest radiographs in those at risk for Pneumocystis jiroveci pneumonia (PCP)

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Similar to other alkylating dugs, AEs are related to its effects on rapidly dividing cells

Notable AEs

• Most common: nausea/vomiting, constipation, alopecia, fatigue, anorexia, lymphopenia, thrombocytopenia

• Less common: rash, diarrhea, thrombocytopenia

Life-Threatening or Dangerous AEs

• Severe neutropenia and thrombocytopenia

• Toxic epidermal necrolysis and Stevens- Johnson syndrome have been rarely reported

• Opportunistic infections including PCP

• Rarely may cause respiratory failure

Weight Gain

• Unusual