Breast Cancer- Clinical Therapeutics

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Information about Breast Cancer- Clinical Therapeutics

Published on February 17, 2014

Author: Gennosuke24



Breast cancer Clinical therapeutics

PROBLEM 1 Breast Cancer Yang, Sheryl Ray B.

Detection and Evaluation

In stage IIB: • larger than 2 centimeters but not larger than 5 cm. small clusters of breast cancer cells (larger than 0.2 millimeter but not larger than 2 millimeters) are found in the lymph nodes • larger than 2 centimeters but not larger than 5 centimeters. Cancer has spread to 1 to 3 axillary lymph nodes or to the lymph nodes near the breast bone (found during a sentinel lymph node biopsy); or • larger than 5 centimeters. Cancer has not spread to the lymph nodes.

Recurrent Breast Cancer • Recurrent breast cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the breast, in the chest wall, or in other parts of the body.

Tamoxifen is beneficial in postmenopausal women when used alone or in combination with cytotoxic chemotherapy Present recommendation: administer tamoxifen for 5 years of continuous therapy after surgical resection. Postmenopausal women who complete 5 years of tamoxifen therapy should be placed on an aromatase inhibitor such as anastrozole for at least 2.5 years In women who have completed 2–3 years of tamoxifen therapy, treatment with an aromatase inhibitor for a total of 5 years of hormonal therapy is now recommended

Metastatic Breast Cancer Radiation therapy, hormonal therapy, and chemotherapy have all been used in the treatment of metastatic breast cancer to palliate the patient and possibly prolong survival. Palliation is the primary goal of therapy: the easiest, least toxic treatment that can provide the best possible response is generally preferred. • metastasize to virtually any site • most common sites: bone, lung, pleura, liver, soft tissue, and the central nervous system. • The choice of therapy for metastatic disease is based on the site of disease involvement and the presence or absence of certain patient characteristics.

Chemotherapy Chemotherapeutic drugs are most commonly used as palliative therapy in patients who would not be expected to respond to hormonal therapy

Radiation Radiation therapy is primarily used to control symptomatic disease such as bone metastases, metastatic brain lesions, and spinal cord compressions.

Hormonal therapy The goal of hormonal therapy is to reduce the stimulation of the tumor cells by estrogen. Tamoxifen, has been the adjuvant hormonal therapy most commonly used. most common side effects: hot flashes and vaginal discharge, but an increased risk of thromboembolic events and endometrial cancer can also occur. Fulvestrant, an injectable pure estrogen antagonist, has also shown activity in patients with hormone-receptorpositive disease progressing on hormonal therapy.

Efficacy Safety Suitability Cost Antiestrogen Tamoxifen +++ selective estrogen receptor modulator or SERM ++ Disease flare, hot flashes; rare: thrombophlebitis, ocular abnormalities, endometrial cancer ++ premenopausal and postmenopausal women (and men) with ER-positive earlystage breast cancer 1,40 0 Aromatase Inhibitors 3rd gen: anastrazole +++ Blocking aromatase in fat tissue that is responsible for making small amounts of estrogen in postmenopausal women +++ Hot flashes, nausea, vomiting, headache, fatigue; rare: bone fractures, musculoskeletal disorders +++ +++ initial therapy for metastatic 2750 hormone-sensitive breast cancer treat postmenopausal women with advanced breast cancer whose disease has worsened after treatment with tamoxifen Pure Estrogen Antagonist Fulvestrant +++ +++ Hot flashes, headache, nausea, vomiting, injection site reactions ++ postmenopausal women with metastatic ER-positive breast cancer after treatment with other antiestrogens +++ 28,0 00

Median duration of response to the first attempt at hormonal manipulation is usually in the range of 9 to 12 months. First-line hormonal therapy should be administered for at least 6 to 8 weeks before disease response is assessed. If a patient becomes refractory to hormonal therapy at any time, chemotherapy should be given.

Natural product cancer chemotherapy drugs: Clinical activity and toxicities DRUG MOA TAXANE Inhibits mitosis Paclitaxel ANTHRACYCLINE Doxorubicin Oxygen free radicals bind to DNA causing single- and doublestrand DNA breaks; inhibits topoisomerase II; intercalates into DNA CLINICAL APPLICATIONS ACUTE TOXICITY Breast cancer, nonsmall cell and small cell lung cancer, ovarian cancer, gastroesophageal cancer, prostate cancer, bladder cancer, head and neck cancer Nausea, vomiting, hypotension, arrhythmias, hypersensitivity Myelosuppression, peripheral sensory neuropathy Nausea, red urine (not hematuria) Cardiotoxicity , alopecia, myelosuppre ssion, stomatitis Breast cancer, Hodgkin’s and non-Hodgkin’s lymphoma, soft tissue sarcoma, ovarian cancer, non-small cell and small cell lung cancer, thyroid cancer, Wilms’ tumor, neuroblastoma DELAYED TOXICITY

DRUG MOA CLINICAL APPLICATIONS ACUTE TOXICITY Breast cancer, non-small cell lung cancer, prostate cancer, gastric cancer, head and neck cancer, ovarian cancer, bladder cancer Neurotoxicity, Hypersensitiv fluid retention, myelosuppression ity with neutropenia TAXANE Docetaxel Inhibits mitosis Mitomycin Superficial Acts as an bladder cancer, alkylating agent gastric cancer, and forms cross- breast cancer, links with DNA; non-small cell forma- tion of lung cancer, head oxygen free and neck cancer radicals, which (in combination with target DNA radiotherapy) Nausea and vomiting DELAYED TOXICITY Myelosuppression , mucositis, anorexia and fatigue, hemolytic-uremic syndrome

DRUG MOA Inhibits Vinblastine mitosis CLINICAL APPLICATIONS ACUTE TOXICITY DELAYED TOXICITY Myelosuppressio n, mucositis, Hodgkin’s and alopecia, non-Hodgkin’s syndrome of Nausea lymphoma, germ inappropriate and cell cancer, secretion of vomiting breast cancer, antidiuretic Kaposi’s sarcoma hormone (SIADH), vascular events

The American Society of Clinical Oncology (ASCO) breast cancer surveillance guidelines: • Women with a history of breast cancer should perform monthly BSE and undergo annual mammography of both the preserved and contralateral breast. • The patient should also have a complete history and physical examination every 3 to 6 months for the first 3 years after diagnosis, then every 6 to 12 months for 2 years, and then annually.

Bone Pain Problem 2 Zepeda, Monina Mae

Basis for Diagnosis • Chief Complaint: Severe (7 out of 10) hip pain • Bone scan: multiple metastases to the right pelvis • Medications: Ibuprofen 200 to 400 mg PO q4– 6h PRN, calcium carbonate 1,000 mg PO TID with meals

Treatment Objectives • To decrease the severity of pain • To minimize adverse reactions or intolerance to pain management therapies • To improve the patient’s quality of life and optimize ability to perform activities of daily living

Bone  most common site of secondary breast cancer Most common: the spine, skull, pelvis and upper bones of the arms and legs

• Pain is defined as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage • most common symptom that provokes people to seek medical attention

KEY POINTS • Oral route is preferred unless contraindicated • Cancer pain is continuous • Should be scheduled at regular intervals rather than prn • Adjuvant therapy is used to decrease anxiety and fear with chronic pain (e.g. antidepressants)

Opioids • refers broadly to all compounds related to opium, a natural product derived from the poppy • produce analgesia, affect mood and rewarding behavior and alter respiratory, cardiovascular, GI, and neuroendocrine function

Strong opioid agonists • • • • Morphine Hydromorphone Fentanyl Methadone

Drug Efficacy Suitability Safety Cost Morphine ++++ +++ +++ ++++ Hydromorphone ++++ 4-5x ++ +++ ++ Fentanyl +++ 100x ++ +++ +++ Methadone ++++ 0.3x + +++ +

Drug Efficacy Suitability Safety Cost Morphine ++++ ++++ +++ ++++ Hydromorph one ++++ ++++ +++ ++ Fentanyl +++ ++ +++ +++ Methadone ++++ + +++ +

Drug Efficacy Suitability Safety Cost Morphine ++++ ++++ +++ ++++ Hydromorph one ++++ ++++ +++ ++ Fentanyl +++ ++ +++ +++ Methadone ++++ + +++ +

Side Effects • Common: Constipation, nausea, vomiting and somnolence • Mood changes • Addiction and physical dependence • Respiratory complication

Drug Efficacy Suitability Side Effects Safety Cost Morphine ++++ ++++ +++ ++++ • Common: constipation, nausea, vomiting, 60's (P1345.00/pack) miosis and somnolence Hydromorphchanges ++++ ++++ +++ ++ • Mood 28's one (P3640.00/pack) • Addiction and physical dependence • Respiratory depression  most common Fentanyl of death of acute overdose +++ ++ +++ +++ cause 5 × 1's (P2513.00/box) Methadone ++++ + +++ +

DOC: Morphine Sulphate - Prototype opioid agonist - exert major pharmacodynamic effects on mureceptors (strong) and kappa-receptors - Main indication is for preoperative pain and chronic malignant pain

Plan of Action Initiate Morphine Sulphate immediate release 15mg PO q3-4hours If the opiate requirement is determined, switch to a sustained release formulation

Plan of Action Start with: - Senna 1 tablet PO BID - Docusate sodium 100 mg PO BID - Ibuprofen 800mg q8h with food - pamidronate 90 mg IV over 2 hours every 4 weeks (Check SCr prior to each dose)

Monitor Efficacy and Toxicity Report any prolonged adverse events, severe confusion/lightheadedness, or difficulty breathing important to take the pain medication around the clock to prevent the pain from recurring

Hypercalcemia of Malignancy secondary to Bone Metastases Reported by: Edward Philip I. Villanueva, MD, FPCP, FPGS, FPCCP CHAIRMAN PHARMACOLOGY DEPARTMENT

I. Basis for Diagnosis • Breast Cancer: commonly associated with hypercalcemia • Pain on the right hip • Decreased appetite • Increasing fatigue • Constipation • More forgetful • Confusion • Calcium level: 12.5mg/dl (NV: 9.0-10.8mg/dl)

II. Treatment Objectives • To reduce serum calcium level • To reverse signs and symptoms of hypercalcemia • Avoid exacerbation of hypercalemia • Reduce gastrointestinal calcium absortion

III. Management • Therapeutic • Non pharmacologic

Loop diuretics • MOA: Enhances urine flow and also inhibits calcium reabsorption in ascending loop of Henle • A/E: ototoxicity, hypovolemia, K wasting, Hyperuricemia, Hypomagnesemia • Route: Oral, IV

Calcitonin • MOA: Lowers plasma Ca⁺² and Phosphate concentrations, blocking bone resorption and increases urinary calcium excretion by inhibiting renal calcium reabsorption • A/E: Nausea, vomiting • Route: SQ, intranasal, oral

Gallium Nitrate • MOA: Inhibiting bone resorption, reducing serum calcium in Cancer patient • A/E: Nephrotoxicity • Route: Oral

Plicamycin • MOA: Inhibiting bone resorption, reducing serum calcium in Cancer patient • A/E: sudden Thromocytopenia, hemorrhage, hepatic and renal toxicity, hypocalcemia, N/V

Phosphate • MOA: Binds to Calcium ions • A/E: Hypocalcemia, ectopic calcification, acute renal failure and hypotension • Route: Oral, IV

Biphosphonates • MOA: Mimics Pyrophosphate structure. It also inhibits the activation of enzyme Farnesyldiphosphate synthase (FPPS) which utilizes Pyrophosphate • A/E: Upsets the stomach and inflammation, erosion of esophagus, flu-like symptoms and rarely Osteonecrosis of the jaw • Route: Oral, IV

Drug of choice: BIPHOSPHONATES Efficacy Safety Suitability Cost Alendronate +++ +++ ++++ +++ P1,100 Risedronate +++ +++ +++ ++ P1,800 Ibandronate +++ ++ +++ + P17,000 Zolendronate ++++ ++ +++ + P24,000 Pamidronate ++++ +++ +++ ++ P1,700

DOC: Pamidronate • Indication: Osteoclast-mediated bone resorption, tumor associated osteolysis, breast and prostate cancer, hypercalcemia • IV: 60-90mg. Over 4 to 24hrs. • Onset: 24-48hrs. • Peak effect: 5-7days • Half life: 21-35hrs. • Excretion: Kidneys

Non Pharmacologic • Hold calcium supplement • Patient education: – Confusion, decreased appetite, constipation are due to high levels of calcium – Nausea and vomiting are side effects of Pamidronate – Eat small frequent meals to help with the Nausea and vomiting

Type 2 Problem 4 Zagada, Timothy M.

Basis for diagnosis • Type 2 diabetes mellitus for 7 years • 20 packs per year tobacco history • Overweight

Treatment Objectives • Continue control of blood sugar by maintaining normal or near-normal ranges – KeepHbA1C of <7 • Prevent disease and drug related complications

Pharmacologic Intervention • Insulin Therapy • Oral Antidiabetic Regimen – Patients with Type II diabetes are frequently treated with combinations of these drugs and are therefore utilizing multiple strategies

Drug Class Action SULFONYLUREA AND MEGLITINIDES Insulin secretagogue BIGUANIDES Insulin Sensitizer THIAZOLIDINEDIONES Insulin Sensitizer Effects • • Decreased endogenous glucose production Reduces insulin resistance • ALPHA-GLUCDIDASE INHIBITOR Competitive inhibitors of the intestinal α-glucosidases • • GLP-1 AGONISTS reduce circulating glucose increase glycogen,fat, and protein formation Glucagon-like peptide-1 • (GLP-1) receptor agonist • Reduce conversion of starch and disaccharides to monosaccharides reduce postprandial hyperglycemia enhances glucose-dependent insulin secretion inhibits glucagon secretion delays gastric emptying, and decreases appetite Clinical Application DM type 2 DM type 2 DM type 2 DM type 2 DM type 2

Insulin Sensitizers THIAZOLIDINEDIONES (TZDs) • increases insulin sensitivity in adipose tissue, liver, and muscle – do not increase insulin levels and therefore do not induce hypoglycemia – Ex; Rosiglitazone, Pioglitazone • Toxicities: – Fluid retention – edema, anemia

Insulin Sensitizers BIGUANIDES • block breakdown of fatty acids and to inhibit hepatic gluconeogenesis and glycogenolysis • increases insulin receptor activity and metabolic responsiveness in liver and skeletal muscle • Does not induce hypoglycemia, Lowers serum lipids and decreases weight • Adverse effect: GI distress, lactic acidosis • Ex; Metformin

GLP-1 AGONISTS AND MIMETICS • Exenatide- Glucagon-like peptide-1 (GLP-1) receptor agonist – – – – enhances glucose-dependent insulin secretion inhibits glucagon secretion delays gastric emptying, and decreases appetite not orally available and must be injected • Sitagliptin- dipeptidyl peptidase-IV (DPP-IV) inhibitor that slows the proteolytic inactivation of GLP-1 and other incretin hormones – Dose adjustment – Kidney disease

Class Efficacy Safety Suitability Cost THIAZOLIDINED +++ IONES (TZDs) +++ ++++ ++ BIGUANIDES ++++ ++++ ++++ ++++ GLP-1 AGONISTS ++++ +++ ++++ ++ Sulfonylureas +++ +++ +++ +++ A-glucosidase inhibitors +++ +++ +++ ++

Drug Class of Choice • Biguanides and Glucagon-like peptide1 mimetics – Metformin + Sitagliptin

Pharmacologic Intervention • Continue Metformin • Discontinue Rosiglitazone, shift to Sitagliptin • Efficacy monitoring: blood glucose, HbA1C in 3 months • If patient requires hospitalization for worsening dehydration or if renal function declines further – hold metformin

Sitagliptin + Metformin (Janumet) Per 50/500 mg Sitagliptin 50 mg, metformin HCl 500 mg. Per 50/850 mg Sitagliptin 50 mg, metformin HCl 850 mg. Per 50/1000 mg Sitagliptin 50 mg, metformin HCl 1,000 mg Form Janumet 50 mg/1000 mg tab Janumet 50 mg/500 mg tab Janumet 50 mg/850 mg tab Packing/Price (P867.20/pack) (P800.00/pack) (P842.00/pack)

Non pharmacologic Intervention • Counsel KF to; – continue diabetes medications and selfmonitoring. – Remind her of the importance of diet/exercise in the treatment of diabetes. – Remind her to maintain all follow-up appointments for diabetes. – Report any shortness of breath or swelling in the legs to the physician.

Problem 5

Basis for diagnosis • Present in patients medical history • Use of paroxetine (controlled under current regiment) • Decreased appetite over the past few weeks and increasing fatigue. • Slightly confused

Treatment Objectives • Continue monitoring for signs and symptoms of depression • Continue therapy to avoid future episodes

Class Efficacy Safety Suitability Cost SSRI ++++ ++++ ++++ ++++ SNRI ++++ +++ +++ + TCA ++++ + ++ +++ MAOI’s ++++ + + +++

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) • Selectively inhibit reuptake of serotonin – increase synaptic serotonin levels – also cause increased 5HT receptor activation and enhanced postsynaptic responses. – At present, SSRIs are the most commonly prescribed first-line agents in the treatment of both MDD and anxiety disorders. Their popularity comes from their ease of use, tolerability, and safety in overdose.

Pharmacologic Intervention • Continue current regimen – controlled with current regimen – Paroxetine, 20 mg PO daily

Pharmacologic Intervention • Monitoring parameters: signs and symptoms of depression; depression may worsen with new diagnosis and prognosis • adverse events of paroxetine: – Nausea – vomiting – constipation/diarrhea – sexual dysfunction

Non-Pharmacologic Intervention • Counsel KF to continue depression medication unless otherwise directed by her physician. • She should seek a psychologist to discuss her new diagnosis. She should report any new/worsened depression symptoms to her physician.

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