THERAPEUTICS

Brands

• BiCNU, Gliadel (wafer)

Generic?

• Yes (as infusion)

Class

• Antineoplastic agent

Commonly Prescribed for

(FDA approved in bold)

• Brain tumors (including glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic tumors)

• Multiple myeloma

• Hodgkin's disease

• Colorectal carcinoma

• Melanoma

How the Drug Works

• A nitrosourea that alkylates DNA and RNA. Drug metabolites may be responsible for clinical effectiveness and toxicity

How Long Until It Works

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

If It Works

• Wafer is only used postoperatively

• Infusions may be continued every 6–8 weeks

If It Doesn't Work

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

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Most patients will receive co-treatment with radiotherapy

• For glioblastomas, carmustine is usually given after treatment with temozolomide has ceased to be effective

• Alkyl guanine transferase inhibitors such as O-6-benzylguanine may increase effectiveness by inhibiting DNA repair

Tests

• Obtain pulmonary function testing before using

• Monitor CBC (platelets and white blood cells especially) weekly

• Monitor liver function tests and renal function periodically or as symptoms arise

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Similar to other alkylating dugs, AEs are related to carmustine's effects on rapidly dividing cells

Notable AEs

• Most common: leukopenia, thrombocytopenia, nausea, vomiting, headache

• Less common: abdominal pain, vision changes, allergic reactions, anemia

Life-Threatening or Dangerous AEs

• Pulmonary fibrosis: may be delayed

• Azotemia and renal failure (relatively rare)

• Severe hepatic toxicity (rare)

• Wafer only: CSF leak, intracranial hypertension

• Leukemia or bone marrow dysplasias

Weight Gain

• Unusual

Sedation

• Unusual

What to Do About AEs

• Leukopenia peaks at 5–6 weeks and thrombocytopenia at 4 weeks. These are used for evaluating subsequent doses