breast cancer- clinical therapeutics
DESCRIPTION
Breast cancer Clinical therapeuticsTRANSCRIPT
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Breast CancerYang, Sheryl Ray B.
PROBLEM 1
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Detection and Evaluation
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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.
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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.
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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
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Metastatic Breast CancerRadiation 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.
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Chemotherapy
Chemotherapeutic drugs are most commonly used as palliative therapy in patients who would not be expected to respond to hormonal therapy
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Radiation
Radiation therapy is primarily used to control symptomatic disease such as bone metastases, metastatic brain lesions, and spinal cord compressions.
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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-receptor- positive disease progressing on hormonal therapy.
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Efficacy Safety Suitability Cost
Anti-estrogen 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 early-stage breast cancer
1,400
Aromatase Inhibitors3rd gen: anastrazole
+++Blocking aromatase in fat tissue that is responsible for making small amounts of estrogen in post-menopausal women
+++Hot flashes, nausea, vomiting, headache, fatigue; rare: bone fractures, musculoskeletal disorders
+++initial therapy for metastatic hormone-sensitive breast cancertreat postmenopausal women with advanced breast cancer whose disease has worsened after treatment with tamoxifen
+++2750
Pure Estrogen AntagonistFulvestrant
+++ +++Hot flashes, headache, nausea, vomiting, injection site reactions
++postmenopausal women with metastatic ER-positive breast cancer after treatment with other antiestrogens
+++28,000
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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.
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Natural product cancer chemotherapy drugs: Clinical activity and toxicities
DRUG MOA CLINICAL APPLICATIONS ACUTE TOXICITY DELAYED TOXICITY
TAXANEPaclitaxel Inhibits mitosis
Breast cancer, non-small cell and small cell lung cancer, ovarian cancer, gastroesophageal cancer, prostate cancer, bladder cancer, head and neck cancer
Nausea, vomiting, hypotension, arrhythmias, hypersensitivi-ty
Myelosupp- ression, peripheral sensory neuropathy
ANTHRA-CYCLINEDoxorubi- cin
Oxygen free radicals bind to DNA causing single- and double-strand DNA breaks; inhibits topoisomerase II; intercalates into DNA
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
Nausea, red urine (not hematuria)
Cardiotoxicity, alopecia, myelosuppression, stomatitis
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DRUG MOA CLINICAL APPLICATIONS
ACUTE TOXICITY
DELAYED TOXICITY
TAXANEDocetaxel Inhibits mitosis
Breast cancer, non-small cell lung cancer, prostate cancer, gastric cancer, head and neck cancer, ovarian cancer, bladder cancer
Hypersensitivity
Neurotoxicity, fluid retention, myelosuppression with neutropenia
Mitomycin
Acts as an alkylating agent and forms cross-links with DNA; forma- tion of oxygen free radicals, which target DNA
Superficial bladder cancer, gastric cancer, breast cancer, non-small cell lung cancer, head and neck cancer (in combination with radiotherapy)
Nausea and vomiting
Myelosuppression, mucositis, anorexia and fatigue, hemolytic-uremic syndrome
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DRUG MOA CLINICAL APPLICATIONS
ACUTE TOXICITY
DELAYED TOXICITY
Vinblastine Inhibits mitosis
Hodgkin’s and non-Hodgkin’s lymphoma, germ cell cancer, breast cancer, Kaposi’s sarcoma
Nausea and vomiting
Myelosuppression, mucositis, alopecia, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), vascular events
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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.
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Bone PainProblem 2
Zepeda, Monina Mae
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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
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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
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Bone most common site of secondary breast cancer
Most common: the spine, skull, pelvis and upper bones of the arms and legs
http://orthoinfo.aaos.org/figures/A00654F08.jpg
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• 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
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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)
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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
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Strong opioid agonists
• Morphine• Hydromorphone• Fentanyl• Methadone
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Drug Efficacy Suitability Safety Cost
Morphine ++++ +++ +++ ++++
Hydromor-phone
++++4-5x
++ +++ ++
Fentanyl +++100x
++ +++ +++
Methadone ++++0.3x
+ +++ +
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Drug Efficacy Suitability Safety Cost
Morphine ++++ ++++ +++ ++++
Hydromorphone
++++ ++++ +++ ++
Fentanyl +++ ++ +++ +++
Methadone ++++ + +++ +
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Drug Efficacy Suitability Safety Cost
Morphine ++++ ++++ +++ ++++
Hydromorphone
++++ ++++ +++ ++
Fentanyl +++ ++ +++ +++
Methadone ++++ + +++ +
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Side Effects
• Common: Constipation, nausea, vomiting and somnolence
• Mood changes• Addiction and physical dependence• Respiratory complication
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Side Effects
• Common: constipation, nausea, vomiting, miosis and somnolence
• Mood changes• Addiction and physical dependence• Respiratory depression most common cause
of death of acute overdose
Drug Efficacy Suitability Safety Cost
Morphine ++++ ++++ +++ ++++60's
(P1345.00/pack)
Hydromorphone
++++ ++++ +++ ++28's
(P3640.00/pack)
Fentanyl +++ ++ +++ +++5 × 1's
(P2513.00/box)
Methadone ++++ + +++ +
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DOC: Morphine Sulphate
- Prototype opioid agonist - exert major pharmacodynamic effects on mu-
receptors (strong) and kappa-receptors- Main indication is for preoperative pain and
chronic malignant pain
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Plan of Action
Initiate Morphine Sulphate immediate release 15mg PO q3-4hours
If the opiate requirement is determined, switch to a sustained release formulation
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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)
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Monitor Efficacy and ToxicityReport 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
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Hypercalcemia of Malignancy secondary to Bone Metastases
Reported by: Edward Philip I. Villanueva, MD, FPCP,
FPGS, FPCCP CHAIRMAN PHARMACOLOGY
DEPARTMENT
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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)
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II. Treatment Objectives
• To reduce serum calcium level• To reverse signs and symptoms of
hypercalcemia• Avoid exacerbation of hypercalemia• Reduce gastrointestinal calcium absortion
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III. Management
• Therapeutic• Non pharmacologic
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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
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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
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Gallium Nitrate
• MOA: Inhibiting bone resorption, reducing serum calcium in Cancer patient
• A/E: Nephrotoxicity
• Route: Oral
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Plicamycin
• MOA: Inhibiting bone resorption, reducing serum calcium in Cancer patient
• A/E: sudden Thromocytopenia, hemorrhage, hepatic and renal toxicity, hypocalcemia, N/V
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Phosphate
• MOA: Binds to Calcium ions
• A/E: Hypocalcemia, ectopic calcification, acute renal failure and hypotension
• Route: Oral, IV
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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
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Drug of choice:Efficacy Safety Suitability Cost
Alendronate +++ +++ ++++ +++P1,100
Risedronate +++ +++ +++ ++P1,800
Ibandronate +++ ++ +++ +P17,000
Zolendronate ++++ ++ +++ +P24,000
Pamidronate ++++ +++ +++ ++P1,700
BIPHOSPHONATES
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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
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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
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Type 2
Problem 4
Zagada, Timothy M.
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Basis for diagnosis
• Type 2 diabetes mellitus for 7 years• 20 packs per year tobacco history• Overweight
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Treatment Objectives
• Continue control of blood sugar by maintaining normal or near-normal ranges – KeepHbA1C of <7
• Prevent disease and drug related complications
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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
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Drug Class Action EffectsClinical
Application
SULFONYLUREA AND MEGLITINIDES Insulin secretagogue
• reduce circulating glucose • increase glycogen,fat, and
protein formation DM type 2
BIGUANIDES Insulin Sensitizer Decreased endogenousglucose production
DM type 2
THIAZOLIDINEDIONES Insulin Sensitizer Reduces insulin resistance DM type 2
ALPHA-GLUCDIDASE INHIBITOR
Competitive inhibitors of the intestinalα-glucosidases
• Reduce conversion of starch and disaccharides to monosaccharides
• reduce postprandial hyperglycemia
DM type 2
GLP-1 AGONISTS Glucagon-like peptide-1 (GLP-1) receptor agonist
• enhances glucose-dependent insulin secretion
• inhibits glucagon secretion• delays gastric emptying, and
decreases appetite
DM type 2
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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– weight gain– macular edema– bone fractures in women – cannot use if CHF, hepatic disease
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Insulin SensitizersBIGUANIDES• 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
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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
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Class Efficacy Safety Suitability Cost
THIAZOLIDINEDIONES (TZDs)
+++ +++ ++++ ++
BIGUANIDES ++++ ++++ ++++ ++++
GLP-1 AGONISTS
++++ +++ ++++ ++
Sulfonylureas +++ +++ +++ +++
A-glucosidase inhibitors
+++ +++ +++ ++
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Drug Class of Choice
• Biguanides and Glucagon-like peptide-1 mimetics– Metformin + Sitagliptin
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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
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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 Packing/Price
Janumet 50 mg/1000 mg tab (P867.20/pack)
Janumet 50 mg/500 mg tab (P800.00/pack)
Janumet 50 mg/850 mg tab (P842.00/pack)
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Non pharmacologic Intervention
• Counsel KF to;– continue diabetes medications and self-
monitoring. – 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.
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Problem 5
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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
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Treatment Objectives
• Continue monitoring for signs and symptoms of depression
• Continue therapy to avoid future episodes
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Class Efficacy Safety Suitability Cost
SSRI ++++ ++++ ++++ ++++
SNRI ++++ +++ +++ +
TCA ++++ + ++ +++
MAOI’s ++++ + + +++
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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.
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Pharmacologic Intervention
• Continue current regimen – controlled with current regimen– Paroxetine, 20 mg PO daily
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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
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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.