NU 341 Anticancer Drugs

Breast Cancer

-affects 1 in 8 women

Tx include: traditional chemo, radiation, surgery, immunotherapy, hormonal drugs

Antiestrogen Drugs

Tamoxifen, Toremifene, Fulvestrant

-tumor cells must have estrogen receptors

Estrogen stimulates tumor cells

-by blocking estrogen receptor, tumor growth is stifled

-as cell death outpaces new growth, tumors shrink

Tamoxifen (Soltamox)

Used for prevention and tx of breast cancer

Prevention: for women at high risk

Tx continues for several years to reduce recurrence

Gold standard for endocrine tx of cancer

Effective for both pre-menopausal and post

AE:

-menstrual irregularities, hot flashes, fluid retention

-DVT, PE, CVA

-Endometrial CA

Aromatase Inhibitors

Tumor cells must have estrogen receptors

Contraindicated in premenopausal women

-do not block estrogen production from ovaries

No risk of endometrial CA

Little risk of DVT, PE, CVA

Anastrozole, Letrozole, Exemestane

Anastrozole (Arimidex)

Estrogen depletion shrinks the tumor but also causes the side effects: menopausal sx, HTN, MSK pain, osteoporosis, fractures

Drug of choice for postmenopausal women with hormonal cancer as it has fewer side effects then tamoxifen

Prostate Cancer

Most common male cancer

Tx: surgery, radiation, anticancer drugs

Androgen hormones promote tumor growth

-produced in testes, adrenal glans and by tumors

therapy includes reducing exposure to androgens

-drug therapy is most effective

Prostate CA Tx Androgen Deprivation Therapy

-suppress androgen production by testes but not by adrenal glands or the tumors- chemical castration

-limited values after 18-24 months, disease progression begins to resume

Gonadotropin- Releasing hormone (GnRH) agonists

-Leuprolied, Triptorelin, Goserelin, Histrelin

Gonadotropin- Releasing Hormone Antagonists (GnRH)

-Degarelix

Leuprolide (Lupron depot)

-can be given SQ daily, IM weekly or monthly

SE: hot flashes, ED, gynecomastia, loss of libido, loss of muscle mass, DM, MI, CVA, osteoporosis

Androgen receptor blockers are used in conjunction to block androgen from adrenal and the tumor

Traditional vs Targeted Therapy

Cancer cells: fast growing, invasive

Traditional Chemo: systemic, generalized, cytotoxic: kills healthy cells, numerous SE

Targeted Therapy: more specific action than traditional cancer chemo

Targeted Therapy Anticancer Drugs

Targeted therapy takes advantage of biologic features particular to cancer cells and targeting specific mechanisms

-defined as drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression

Targeted Therapy

Breakthrough in cancer Tx

Can be taken alone or with traditional chemo

Some taken PO, at home

The cancer MUST be susceptible to the action of the med

-required a specific molecular target as the recipient of their effects

-requires testing to verify the cancer cells have the molecular makeup

Expensive

Continues to be an area of research with new drugs and new applications for Tx

Genetic control over cell division

Signal transduction

Tyrosine kinases

Transcription factors

Cyclins

Genetic control over cell death

Apoptosis- programmed cell death, designed to ensure that tissues contain only healthy and optimally functional cells

-regulated by different gene products

Growth regulation and cancer

-loss of genetic control of cell growth

-loss of apoptosis

Epidermal Growth Factor Tyrosine Kinase Inhibitors (EGFRIs)

Action: inhibit kinase indirectly, inhibit downstream signal transaction pathway for cell division

-results in severely limited cell proliferation

Drugs:

Cetuximab (Erbitux) IV

-SE: interstitial lung disease- teach pts to report breathing difficulty

Gefitinib (Iressa)- PO

-St. Johns Wort decrease levels

Tyrosine Kinase Inhibitors (TKIs)

Action: stop proliferation of cancer cells, resistance to drugs can develop

The cancer MUST be susceptible to the action of the med

Gold standard for treatment of chronic myeloid leukemia (CML)

Imatinib mesylate (Gleevec)

SE/AR:

-N/V, HA, fatigue

-hematologic alterations: neutropenia, thrombocytopenia

-CBC done regularly- q week initially

Contents of the tablet are toxic

-pt or RN should wear gloves if the tablets are crushed or broken

Multi-Tyrosine Kinase Inhibitors

Action: directly inhibit activity of specific kinases in cancer cells and in cancer cell vasculature

Drug: Sorafenib (Nexavar)

-for tx of renal cell, hepatocellular and thyroid carcinomas

SE/AR:

-diarrhea, fatigue, dysrhythmias, high risk of bleeding

BRAF V600E Kinase Inhibitors

Vemurafenib (Zelboraf)

-for tx of metastatic melanoma

-suppresses tumor growth

-melanoma must be susceptible

SE: cutaneous squamous cell carcinoma, Steven-Johnson syndrome, fatal dysrhythmias

CD-Directed Antibodies

Rituximab (Rituxan)- tx of B-cell non-Hodgkin's lymphoma, B-cell chronic lymphocytic leukemia

Stimulates the immune system to cause lysis of cancer cells

Severe SE

-hypotension, bronchospasm, angioedema- have epi and other emergency support available when infusing, monitor closely

Tumor Lysis Syndrome- 12-24 hours after infusion, electrolyte abnormalities, renal failure

-teach pt to report N/V, muscle cramps and decreased urination

Angiogenesis Inhibitors

Action: reduces vascular growth that supports the tumor (s) and inhibits metastatic disease progression, doesn't kill tumor, however prevents further growth

Drugs:

-Bevacizumab (Avastin)- tx of colon, lung, brain, renal and cervical/ovarian CA

SE/AE:

-Boxed warning for GI perforations, wound dehiscence, impaired wound healing, hemorrhage and fistula formation after surgery.

-The drug should not be used within 28 days after major surgery

Proteasome Inhibitors

Action: suppresses cancel cell division, promoting apoptosis

Drug: Bortezomib (Velcade): tx of multiple myeloma

SE/AR:

-N/V, anorexia

-hematologic issues

-peripheral neuropathy

-St. John's wort may decrease levels of bortezomib

Cyclophosphamide

Action: Cross-links DNA → inhibits replication → cell death (cell cycle nonspecific)

Tx: Lymphomas, leukemias, Breast cancer, Ovarian cancer, Autoimmune diseases (e.g., Systemic Lupus Erythematosus)

SE:

-Hemorrhagic cystitis (from toxic metabolite acrolein)

-Myelosuppression

-Infertility

-↑ risk of secondary malignancies

Prevent cystitis with Mesna + hydration

Used in many cancers + autoimmune diseases

Vincristine

Tx:Leukemias (especially ALL), Lymphomas

MOA: Inhibits microtubules → stops mitosis

SE: Peripheral neuropathy, Constipation

Filgastim

Tx: chemo-induced neutropenia, bone marrow recovery

MOA: stimulates neutrophil production

SE: bone pain

Odansetron

Tx: chemo induced N/V, post-op nausea

MOA: 5-HT3 antagonist

SE: Q-T prolongation

Dexmethasone

Tx: chemo-induced nausea, brain tumors (decreases edema), leukemia, lymphoma, inflammatory conditions

SE: hyperglycemia, mood changes