Unit 12 Chemo and Hormone Therapy

Primary Prevention of Cancer

Interventions that keep cancer from developing:

• Health counseling

• Elimination of tobacco

• Receive HPV vaccination to prevent cervical cancer

• Maintain healthy diet

• Decreasing excess stress

• Avoiding chronic or prolong exposure to direct sunlight wearing protective clothing or sunscreen.

Secondary Prevention of Cancer

Includes interventions leading to the discovery and control of cancerous or precancerous lesions while they are small and localized:

• Pap smear

• Colonoscopy

• Mammograms

• Prostate screening

• Monthly breast exams

• Regular skin self exams

What is cancer staging?

Where cancer is located; extent of its invasion

• Done to determine the extent to which cancer has invaded the body; helps determine the best course of therapy and predict treatment outcomes.

What is cancer grading?

Looks at differentiation of the cancer cells.

• Cancer cells change and become less differentiated in both structure and function

• Unlike staging, grading may change over time as the tumor evolves

Chemotherapy

Systemic: non specific cell destruction

• Goal is to kill as many cancer cells as possible while sparing as many as possible normal cells

• Given for cure, control, and palliation

• Some work in all cell cycles to kill cells, some work specifically in one cell cycle

• Can be given via all routes of administration

• Associated with multiple toxicities

What does chemotherapy do to the hematologic system?

Stem cells in the bone marrow are destroyed by chemo, which results in myelosuppression.

• Most common dosing limiting adverse effect of chemotheraoy

• Severe bone marrow suppression is a contraindications to chemo

• Will cause blood counts to decrease until they reach their nadir (lowest point)

  • WBCs- leukopenia, RBCS, anemia, platelets: bleeding

  • During the nadir, patients will be most susceptible to symptoms caused by the myelosuppression

GI toxicity of chemo

Severe nausea and vomiting.

• GI tract mucosa is very sensitive to the effects of chemotherapeutic agents; the mucosa commonly becomes inflamed , a condition known as mucositis.

  • Painful ulcerations along mouth and esophagus

  • Difficulty eating and swallowing

  • GI bleeding

  • Intestinal infections

  • Severe diarrhea

Cyclophosphamide (Cytoxan)

Alkylating Agent

MOA: Binds to DNA and forms croos-links, preventing synthesis of DNA and RNA and protein.

Cyclophosphamide Indications

• Very broad spectrum of action; approved in combination with other antineoplastics

• Treats Hodgkin’s and NHL, leukemia, ovarian, breast, multiple myeloma, neuroblastoma, sarcomas, and others

• Off-label uses: immunosuppressive indications for prophylaxis of organ transplant rejection, nephrotic syndrome, severe rheumatoid arthritis, lupus, scleroderma

Cyclophosphamide Adverse Effects

• Headache

• Nausea, vomiting, stomatitis

• Rash, fluid retention

• Myelosuppression

• Alopecia (50% total baldness)

• Jaundice, skin changes

• Risk of secondary malignancies

• Cardiotoxicity, pulmonary fibrosis

• Sterility in both genders

• Hemorrhagic cystitis- life threatening

  • medication should always be given with increased fluids, urine dipstick monitoring, and a bladder protectant drug (mesna)

Cyclophosphamide Contraindications

• Pregnancy

• Lactation

• Severe myelosuppression

• Recent steroid use

• Caution with renal or hepatic impairment

Cyclophosphamide Interactions

• Other drugs with hepatic metabolism

• Additive immunosuppressive effects with other agents that cause bone marrow toxicity

• Increases anticoagulation effect with other anticoagulants

• St. John’s Wort may increase the toxic effects

Cisplatin (Platinol)

Alkylating Agent

Made from heavy metals, chloride and ammonia; used as part of a combo chemo regimen

Only IV

First dose can. cause anaphylaxis

• Stay at bedside

• Emergency kit on hand, suction, crash cart

Cisplatin BBW

• Myelosuppression (25-40%)

• Ototoxicity- sometimes permanent

  • Tinnitus, high-frequency hearing loss

• Anaphylaxis

• Nausea, vomiting

• Nephrotoxicity- major dose limiting toxicity

  • Watch for acute renal failure

    • Strict I/Os, increase fluid intake, check renal labs

Methotrexate (MTX, Rhematrex)

Antimetabolite

MOA: Reduce folate → interfering with DNA synthesis

Methotrexate Indications

• Primarily use as an antineoplastic agent in combination therapy to maintain induced remissions after surgical resection or amputation. Used for many different cancers

• Used for severe RA that doesn’t respond to NSAIDs and at least one other RA drug; psoriasis that is unresponsive to other treatment

• Off-label uses include autoimmune disorders such as Crohn’s, ulcerative colitis, and lupus

• May be used for abortions with misoprostol or for ectopic pregnancy

Methotrexate BBW

• Combination with NSAIDs may cause severe or fatal myelosuppression

• Myelosuppression is the dose limiting toxicity

• Hepatotoxic and may cause liver cirrhosis with prolonged use

• Pulmonary toxicity; dyspnea, acute or chronic interstitial pneumonitis

• Dermatologic reactions (toxic epidermal necrolysis, SJS)

• Ulcerative stomatitis and diarrhea requires suspension of therapy because they may lead to hemorrhagic enteritis

Methotrexate Contraindications

• Existing myelosuppression

• Concurrent hepatotoxic treatment

• Precautious with renal or hepatic impairment

Methotrexate Interactions

Interacts with many drugs; do NOT take OTC pain medications unless directed by PCP; avoid multivitamins (may contain folic acid)

Methotrexate Pregnancy Concerns

Confirmed teratogen; avoid pregnancy during therapy, category X

What medication is given with methotrexate?

Levoleucovorin is given asap to decrease toxic effects: “rescues” patients from MTX toxicity

• Leucovorin itself can be fatal to the client if not given in the correct dose at the correct time during methotrexate therapy

Fluorouracil (5-FU)

Antimetabolite

Inhibits DNA/RNA synthesis

• Treats many kinds of tumors, including inoperable tumors

• BBW: myelosuppression

  • nadir on 9-14 days

• Hand-foot syndrome (palmar-plantar erythrodysesthesia 40% of patients receiving IV long term)

• Nausea. vomiting, and stomatitis

Doxorubicin (Adriamycin)

Antitumor Antibiotics

MOA: wide spectrum or antitumor activity

Doxorubicin Indications

• Considered one of the most effective single agents against solid tumors; also part of many combination treatments

• Approved for use in patients with AIDS-related Kaposi’s sarcoma

Doxorubicin Contraindications

• Pre-existing myelosuppression

• Pre-existing cardiac disease

• Use caution with hepatic and renal impairment

Doxorubicin Adverse Effects

• Severe N/V, mucositis, rash, excessive lacrimation, hepatotoxicity, anaphylaxis, complete alopecia, and radiation recall phenomenon (possible reaction if patient has had prior radiation therapy)

• Turns urine and tears a red color; harmless but anxiety provoking

• Severe vesicant

  • Treat immediately with ice packs to reduce reabsorption of the drug

  • Dexrazoxane also given as a reversal agent

Doxorubicin BBW

• Significant cardiotoxicity; acute and chronic; heart failure may occur months to years after therapy

• Limiting dosing based on ejection fraction and BMI

  • Do baseline and post-therapy echocardiograms

• Dexrazoxane given specifically to prevent and treat cardiotoxicity related to the medication or extravasation of this med

• Severe myelosuppression may occur and is the dose limiting toxicity

Vincristine (Oncovin)

Natural Product

MOA: from periwinkle plant, inhibits division

Vincristine Indications

Approved to treat acute lymphocytic leukemia, Hodgkins and non-Hodgkins lymphomas, and more.

Vincristine Interactions

• Concurrent administration with mitomycin (antitumor antibiotic) may cause acute dyspnea and severe bronchospasm; neurotoxicity may occur with peripheral nervous system drugs

Vincristine Route

Only given IV. Has caused fatalities with given intrathecally.

Vincristine Adverse Effects

• Toxic effects even at therapeutic dose

• Neurotoxicity is the major dose-limiting toxicity

  • Motor difficulties, severe and often permanent peripheral neuropathies, paresthesias, weakness, nerve palsies, and decreased reflexes

• CNS effects may include seizures, depression, hallucinations, and coma

• GI toxicity includes N/V, anorexia, stomatitis, severe constipation, abdominal pain, hepatotoxicity, and paralytic ileus

• Rash and alopecia

Vincristine BBW

• Myelosuppression may be severe

• Extravasation occurs, treat with warm compresses and hyaluronidase

• Cold packs will significantly increase the toxicity of the vinca alkaloids

Vincristine Contraindications

• People of childbearing age

• Active infection

• Pregnancy

• Lactation

• Caution with leukopenia, other drugs with neurotoxic properties

Tamoxifen (Nolvadex, Soltamox)

MOA: binds to estrogen receptors, producing agonist effects in some tissues (bone) and antagonist effects in other tissues (breast)

Tamoxifen Indications

• Used as an anti-estrogen for estrogen-receptive positive tumors

• Only antineoplastic approved for the prophylaxis in women who are at high risk of developing breast cancer

• Used off-label to induce ovulation

Tamoxifen Interactions

• Extensively metabolized by hepatic enzymes

• Used with warfarin increases bleeding

• SSRIs may decrease effectiveness

• Should not be taken with oral contraceptives

• Black cohosh should not be taken unless approved

Tamoxifen Contraindications

• Anticoagulant therapy

• Endometrial hyperplasia

• Thromboembolic disease

• Pregnancy

• Lactation

Tamoxifen Adverse Effects

• Few serious adverse side effects other than nausea and vomiting

• Hot flashes

• Vaginal discharge

• Irregular menses

• Vaginal bleeding

• Fluid retention

• Headaches

• Weight loss

Tamoxifen BBW

• Increased risk of endometrial cancer

• Slightly increased risk of thromboembolic disease