DOXORUBICIN

ANTITUMOR ANTIBIOTIC

DOXORUBICIN
Drug Class: Antitumor antibiotic Trade names: Adriamycin Pregnancy Category: D Dosage: 60-75 mg/m2 as a single dose every 21 days or 30 mg/m2 IV for 3 days ever 4 wk. when used in combination therapy: 40-50 mg/m2 as a single IV bolus every 21 to 28 days. Safety and efficacy have not been established for children. Reduce dose with renal impairment.

Contraindications
Pregnancy Severe cardiac disease. Cardiac status and cardiac ejection fraction should be tested before starting doxorubin therapy. Do not exceed a lifetime cumulative dose of 550 mg/m2 (450 mg/m2 if client has prior chest irradiation or is receiving cyclophosphamide). Dexrazoxane (Zinecard) is used to help prevent or lessen cardiac damage. Caution: hepatic and renal impairment

DOXORUBICIN
Therapeutic Effects / Uses: breast, bladder, ovary, and lung cancers leukemias Lymphomas Soft tissue and bone sarcoma. Mode of action: inhibits DNA and RNA synthesis; has immunosuppressant activity

Side Effects
Stomatitis Anorexia Nausea Vomiting Diarrhea Rash Alopecia Doxorubicin is a potent vesicant. May cause a flare reaction. Nausea and vomiting are dose-related and may begin 1-3 h after administration. Causes colored urine (pink to red) for up to 48 h. May cause radiation recall to previously irradiated skin.

Adverse Reactions
Esophagitis Anemia Hyperpigmentation of nails, tongue, and oral mucosa, especially in African Americans. Drug is teratogenic, mutagenic, and carcinogenic. Life threatening: thrombocytopenia, luekopenia, cardiotoxicity, congestive heart failure, electrocardiogram changes, severe myelosuppression, anaphylaxis

Nursing Assessment
Assess complete blood count (CBC), differential, and platelet count weekly. Drug may be withheld if RBC, WBC, or platelet counts drops below predetermined levels. Conduct thorough physical assessment; document findings. Assess temperature; fever may be an early sign of infection. Assess plans for pregnancy (if appropriate).

Nursing Interventions
Monitor blood counts and laboratory values. Assess cardiac status. Handle drug with care during preparation and administration. Avoid contact with drug. Monitor IV site frequently. Doxorubicin is a severe vesicant whose effects are not immediately apparent. Give drug through a large bore, quickly running IV infusion. Tissue necrosis may occur 3 to 4 weeks after infiltration into tissue. Extravasation produces severe pain. If this occurs, apply ice pack and notify health care provider. Administer antiemetic 30 to 60 minutes before chemotherapy.

Nursing Interventions
Monitor for changes in urine color (pink to red). The drug is red and is excreted in the urine. Offer client food and fluids that may decrease nausea (e.g., cola, crackers, ginger ale). Plan small, frequent meals. Administer prophylactic antibiotics to prevent infection. Offer analgesics for pain as prescribed. Maintain strict medical asepsis during dressing changes and invasive procedures. Support good oral hygiene; brush teeth with soft toothbrush and use waxed dental floss. Monitor fluid intake and output and nutritional intake.

VINCRISTINE
Plant Alkaloid

VINCRISTINE
Drug Class: Miotic inhibitor / Plant alkaloid Trade names: Oncovin Pregnancy Category: D Dosage: A: IV: use only via free flowing IV catheter. 1.4 mg/m2, weekly. C: IV: use only via free flowing IV catheter. 2 mg/m2. For children 10 kg, starting dose is 0.05 mg/kg, weekly. If peripheral neuropathy occurs, reduction or discontinuance of therapy may be needed.

Contraindications
FATAL if given intrathecally. Do not give to patients receiving radiation therapy through ports into the liver. Hypersensitivity. Do not give to patients with Charcot-MarieTooth Syndrome. Caution: pregnancy, liver or kidney disease, neuromuscular disease, or infection

Therapeutic Effects / Uses

Acute leukemia Hodgkins disease non-Hodgkins lymphoma Neuroblastoma Rhabdomyosarcoma Ewings sarcoma Wilms tumor multiple myeloma chronic leukemia thyroid cancer brain tumors Mode of action: affects cells in the M phase of the cell cycle and inhibits mitosis

Side Effects: peripheral neuropathy loss of DTR Phlebitis Constipation Cramps Nausea & vomiting muscle weakness reversible alopecia.

Adverse Reactions: sensory loss hypotension, visual disturbances, ptosis, ileus, SIADH, hyponatremia, hyperuricemia, sever local reaction with extravasation, fever Life threatening: intestinal necrosis, seizures, coma, acute bronchospasm, bone marrow depression

Nursing Assessment:
Assess baseline condition of patient before and during chemotherapy treatment. Assess complete blood count (CBC), differential, and platelet count weekly. Monitor bilirubin levels. Dose may be reduced if bilirubin levels are 1.5 mg/dl. Conduct thorough physical assessment; document findings. Be especially aware of evidence of neurotoxicity, because this is a dose- limiting toxicity. Assess for signs of peripheral neuropathy loss of DTR, foot drop, slapping gait, difficulty walking.

Nursing Assessment:
Monitor bowel function. Autonomic neuropathy may lead to constipation and paralytic ileus. The use of vincristine (Oncovin) and narcotic analgesics may increase the risk of constipation. Assess temperature; fever may be an early sign of infection. Monitor for acute bronchospasm. Assess plans for pregnancy (if appropriate). Evaluate patient/family/caregiver knowledge of drug therapy.

Nursing Interventions
Monitor blood counts and laboratory values. Assess bowel function. Administer stool softener or laxative as prescribed. Monitor for signs of peripheral neuropathy (numbness or tingling in fingers or toes), sensory loss, loss of DTR, paresthesia, foot drop, wrist drop, ataxia. Assess IV site carefully. Vincristine (Oncovin) is a sever vesicant whose effects are not immediately apparent. Give drug through a large bore, quickly running IV infusion over 1 minute.

Nursing Interventions
Tissue necrosis may occur 3 to 4 weeks after infiltration into tissue. Extravasation produces severe pain. Notify health care provider. Apply heat intermittently every two hours for 24 hours. Give hyalurodinase into the infiltrated area, per physician order. Administer antiemetic 30 to 60 minutes before chemotherapy, or as prescribed. Monitor fluid intake and output and nutritional intake. Maintain strict medical asepsis during dressing changes and invasive procedures.

TARGETED THERAPIES TO TREAT CANCER

PROTEASOME INHIBITORS
Intracellular multienzyme complexes that degrade proteins to eliminate the cells of proteins that are not needed. Such proteins regulate transcription, cell adhesion, apoptosis, cell cycle progression, and mitosis. Cancer may develop when these processes become abnormal. Disrupt aspects of cellular structure, promoting apoptosis

Bortezomib (Velcade)
Only available proteasome inhibitor at present Inhibit a specific (26 S) proteasome, altering proteins that regulate cellular growth and division Approved for the treatment of
Multiple myeloma Colorectal cancer Lung cancer

MULTIKINASE INHIBITORS (MKIs)

sorafenib (Nexavar) first approved MKI for treatment of metastatic renal cell cancer (RCC) on December 2005 sunitinib (Sutent) approved for advanced RCC and gastrointestinal stomal tumor (GIST) on January 2006

MULTIKINASE INHIBITORS (MKIs)

temsirolimus newly FDA approved on May 2007 for advanced/poor risk RCC or MCL

ANGIOGENESIS INHIBITORS
Inhibit the formation of blood vessels needed for tumor growth and metastasis bevacizumab (Avastin) - only angiogenesis inhibitor at present - used primarily for metastatic carcinoma of the colon and rectum - can be combined with other chemotherapy drugs for the treatment of breast, prostate, and renal cell cancers.

MONOCLONAL ANTIBODIES
designed to recognize and bind to specific antigens expressed on the surface of the cancer cells work by blocking the growth of the tumor and/or alerting the bodys immune system to attack the cancer cells

THREE TYPES OF MONOCLONAL ANTIBODIES

I. Chimeric antibodies Cetuximab: metastatic colorectal cancer Rituximab: B cell non Hodgkins lymphoma II. Humanized antibodies Gemtuzumab ozogamicin : acute myeloid leukemia III. Fully Human antibodies Trastuzumab: breast cancer