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Cancer
A cellular disorder, clonal origin Progressive accumulation of a mass of cells Progressive invasion of surrounding tissues and organs Ability to metastasize to distant organs
Cancer
Essentially, a genetic disease Mutation of genes:
Cellular Kinetics
Human body contains 5x1013 cells
Cells can either be non dividing and terminally differentiated continually proliferating but may be recruited into cell cycle
- rest
Tumour becomes clinically detectable when there is a mass of 109 cells (1g)
Tumor kinetic
Growth rate depends on:
growth fraction
-percent of proliferating cells within a given system -human malignacy ranges from 20-70% -bone marrow 30 %
tumor growth is exponential chemotherapy treatment is designed to kill in log intervals (kills constant fractions of tumor)
Combination therapy and increased drug dose levels aim at improving ovarian cancer chemotherapy.
Gompertzian Growth
Growth rates are exponential at early stages of development and slower at later stages of development.
Medium size tumour grows more quickly but with smaller growth fraction
Tumor Growth
number of cancer cells
10 12
10 9
time
undetectable cancer
Principle of chemotherapy
First order cell kill theory
- a given dose of drug kills a constant percentage of tumour cells rather than an absolute number
Tumors given less time to grow in between treatments are more likely to be destroyed.
Tumor cell regrowth can be prevented if tumor cells are eradicated using a denser dose rate of cytotoxic therapy.
Principle of chemotherapy
Rationale for combination chemotherapy
Different drugs exert their effect through different mechanisms and at different stages of the cell cycle, thus maximize cell kill Decease the chance of drug resistance
Paraneoplastic syndrome
Syndrome
Systemic
Clinical manifestation
anorexia, cachexia, weight loss, fever hypercalcemia, hyponatremia, hypoglycemia, syndrome digital clubbing,
Endocrine
Cushing Skeletal / connective tissue pulmonary osteoarthropathy Neurolgic / muscular
hypertrophic
myasthenia gravis, Eaton-Lambert syndrome, polymyositis, peripheral neuropathy, subacute cerebellar degeneration
Paraneoplastic syndrome
Syndrome
Clinical manifestation
anemia, polycythemia, leukocytosis, thrombocytosis, deep vein thrombosis dermatomyositis, acanthosis nigricans nephrotic syndrome, glomerulonephritis
Hematologic
Skin Renal
CURATIVE CARE
PALLIATIVE CARE
TIME
ACTIVITY
Different mechanisms of action Different mechanisms of resistance
SAFETY
Compatible side effects
It is easy to kill cancer cells, but the challenge is keeping the patient alive at the same time..!
Modalities of treatment
Local treatment options Surgery Radiation Systemic treatment options Chemotherapy Hormonal therapy Biotherapy Molecular-targeted therapy
Principle of Treatment :
Most anticancer treatment is directed towards killing actively dividing cells.
Impaired immune and hematopoietic function Altered gastrointestinal structure and function
Chemotherapy
Treating cancer with chemical agents Major role in cancer therapy Used to cure and increase survival time Some selectivity for killing cancer cells over normal cells Normal cells most affected: the skin, hair, intestinal tissues, spermatocytes, and blood-forming cells
Chemotherapy Drugs
Antimetabolites Antitumor antibodies Alkylating agents Antimitotic agents Topoisomerase inhibitors Miscellaneous chemotherapeutic agents Combination chemotherapy
Treatment Issues
Drug dosage Drug schedule Drug administration
Gene Therapy
Experimental as a cancer treatment Renders tumor cells more susceptible to damage or death by other treatments Injection into tumor cells, enabling the immune system to better recognize cancer cells as foreign and kill them Antisense drugs
Targeted Therapies
Definition New technology and drugs that allow the cancer treatment to target a certain cancer cell by interfering with the natural functions of tumor growth How they work They target specific parts of a cancer cell or its actions; hand in a glove analogy What it means in cancer treatment Potentially fewer side effects
Targeted Therapies
Monoclonal antibodies: proteins that trigger the bodys pathways involved in cancer growth to fight cancer more effectively.
EGFR: family of receptors found on surface of normal and cancer cells that bind with an epidermal growth factor (EGF) causing cells to divide.
Tyrosine Kinase Inhibitors: Part of the cell that signals it to divide and multiply; enhances cell growth. Still investigational
Adjuvant chemotherapy
a short course of combination chemotherapy in a patient with no evidence of residual cancer after surgery or radiotherapy, given with the intent of destroying a small number of residual tumor cells
Neoadjuvant
chemotherapy given in the preoperative or perioperative period
Primary:
same as neoadjuvant chemotherapy, also applied to chemotherapy given in the absence of intended surgery or radiotherapy
Salvage:
-combination chemotherapy given in a patient who has failed or recurred following a different curative regimen
Palliative:
chemotherapy given to control symptoms or prolong life in a patient in whom cure is unlikely
Induction: combination chemotherapy given with the intent of inducing complete remission when initiating a curative regimen
Consolidation: repetition of the induction regimen in a patient who has achieved a complete remission after induction
Intensification: chemotherapy after complete remission with higher doses, with the intent of increasing the cure rate or remission duration
Maintenance: long-term, low-dose chemotherapy in a patient who has achieved a complete remission
Objective Response Complete Response (CR) Partial Response (PR) Progressive Disease (PD) Stable Disease (SD)
Neoadjuvant chemotherapy
Preservation of the tumor mass as a biologic marker of responsiveness to the drugs
Melanoma Pancreatic cancer Prostate cancer Soft tissue sarcoma Hepatoma Renal cell carcinoma
Alkylating agents:
Antimetabolites:
methotrexate, 5-fluorouracil, nucleoside analogues
Anthracyclines:
doxorubicin, epirubicin
Antimicrotubule agents:
Platinum analogues:
cisplatin, carboplatin
Topoisomerase II inhibitors:
etoposide, tenoposide
Types of chemotherapy
G2 (2-32h) M (0.5-2h)
Vinca alkaloids
Mitotic inhibitors
Taxoids
Alkylating agents
G1 (2-h) G0
Cycle-Specific Agents
DNA
Alkylating agents
DNA transcription
DNA duplication
Intercalating agents
Mitosis
ALKYLATING AGENTS
Cyclophosphamide
alkylation of DNA through the formation of reactive intermediates oral bioavailability 100% T1/2 3-10 hrs -- parent compound, 8.7 hrs -phosphoramide mustard metabolism:
microsomal hydroxylation hydrolysis to phosphoramide mustard (active) and acrolein
Metabolism of Cyclophosphamide
CYCLOPHOSPHAMIDE
HEPATIC CYTOCHROMES P 450
ACTIVATION
INACTIVATION
4-KETOCYCLOPHOSPHAMIDE CARBOXYPHOSPHAMIDE
ALDEHYDE DEHYDROGENASE
4-OH CYCLOPHOSPHAMIDE
ALDOPHOSPHAMIDE
ACROLEIN
PHOSPHORAMIDE MUSTARD
TOXICITY
CYTOTOXICITY
Cyclophosphamide
toxicity:
myelosuppression alopecia pulmonary fibrosis Intake daytime pill cystitis: use MESNA with high-dose therapy SIADH cardiac toxicity leukemogenesis infertility teratogenesis
ANTIMETABOLITES
Methotrexate (MTX)
inhibition of dihydrofolate reductase--->partial depletion of reduced folates polyglutamates of MTX and dihydrofolate inhibit purine and thymidylate biosynthesis metabolism: converted to polyglutamates in normal and malignant tissues elimination: primarily as intact drug in urine, third-space retention
Methotrexate (MTX)
High dose toxicity: rescue by leucovorin Pretreatment with MTX increases 5-FU and ara-C nucleotide formation NSAIDs decrease renal clearance and increase toxicity Reduce dose in proportion to decrease in creatinine clearance NO high-dose MTX to patients with abnormal renal function Monitor plasma conc. of drug and hydrate patients during highdose therapy
Methotrexate (MTX)
toxicity: myelosuppression mucositis renal tubular obstruction and injury in high-dose therapy, requires urine alkalinization and hydration hepatotoxicity in chronic therapy pneumonitis hypersensitivity: rare neurotoxicity
5-fluorouracil (5-FU)
Interferes with RNA synthesis and function inhibition of thymidylate synthase (TS) Affect DNA stability primary T1/2 8-14 min, clearance is faster with infusional schedules, non-linear pharmacokinetics 90% is eliminated by metabolism, <10% unchanged drug renally excreted, dihydropyrimidine dehydrogenase (DPD)
5-FU
Leucovorin increases activity and toxicity Toxicity: GI epithelial ulceration myelosuppression skin toxicity ocular toxicity neurotoxicity cardiac toxicity biliary sclerosis (hepatic arterial infusion of FUDR)
AraC
inhibits DNA polymerase alpha short plasma T1/2 elimination: deamination in liver, plasma and peripheral tissue 100% blocks DNA repair, enhances activity of alkylating agents
AraC
toxicity: myelosuppression
GI epithelial ulceration intrahepatic cholestasis, pancreatitis cerebellar and cerebral dysfunction (highrenal function) conjuctivitis (high-dose) hidradenitis noncardiogenic pulmonary edema
ANTHRACYCLINES
Pleiotropic effects:
Inhibition of dna topoisomerase ii activity Activation of protein kinase c, Generation of reactive oxygen and stimulation of apoptosis
Drug clearance is decreased in the presence of hyperbilirubinemia or patients with marked burden of metastatic tumor in liver
Myelosuppression
Mucositis
Alopecia Cardiac toxicity: acute and chronic, cumulative dose-related (hypertensive heart disease, mediastinal) Severe local tissue damage after drug extravasation
ANTIMICROTUBULE AGENTS
Vinca alkaloids: vincristine, vinblastine, vinorelbine Taxanes: paclitaxel, docetaxel Vinca alkaloids
Inhibit polymerization of tubulin Hepatic metabolism and biliary excretion Patients with abnormal liver function test should be treated with caution
Vinca alkaloids
1971
Pacific Yew: Taxus brevifolia
OH
1986
European Yew: Taxus baccata
Taxanes:
Toxicity: acute hypersensitivity reactions, premedication with corticosteroid and antihistamines (h1 and h2 blockers) neutropenia, thrombocytopenia mucositis (esp. prolonged infusion, 96-hr) alopecia sensory neuropathy cardiac conduction disturbances fluid retention (docetaxel)
PLATINUM ANALOGUES
Cisplatin, carboplatin, oxaliplatin
Cisplatin
Covalent binding to DNA Inactivated by sulfhydryl groups, covalently binds to glutathione, metallothioneins, and sulfhydryls on proteins 25% is excreted during the first 24 hrs, renal > 90%, bile < 10%
Cisplatin
toxicity: renal insufficiency with Mg2+ wasting, monitor electrolytes, Mg2+, Ca2+, use with caution in the presence of other nephrotoxic drugs
nausea and vomiting peripheral neuropathy auditory impairment myelosuppression visual disturbance (rare) hypersensitivity (rare) seizures (rare)
Carboplatin
drug is primarily excreted, only a small fraction is metabolized 90% excreted in urine in 24 hrs toxicity: myelosuppression, esp. thrombocytopenia nausea and vomiting nephrotoxicity at high doses and in patients with prior renal dysfuction reduce dose in proportion to reductions in creatinine clearance
Oxaliplatin
Greater distribution to tissue than cisplatin (50 times) Excrete by urine in metabolite form Never reconstitute in 0.9% NaCl (unstable) Toxicities :
neurotoxic peripheral sensory neuropathy N/V/D
TOPOISOMERASE II INHIBITORS
Etoposide
Inhibition of DNA topoisomerase II Terminal t1/2 6-8 hrs Hepatic metabolism, renal excretion 35-40% Reduced dose proportionate to creatinine clearance
Toxicity: neutropenia, thrombocytopenia (mild), alopecia hypersensitivity, mucositis (high doses)
CAMPTOTHECINS
Irinotecan (CPT-11) Topotecan Irinotecan
inhibit topoisomerase I by stabilizing the cleavable complex in which the enzyme is covalently bound to DNA at a single-stranded break site is a prodrug which requires enzymatic cleavage by the carboxylesterase converting enzyme to generate the biologically active metabolite, SN-38
Irinotecan
elimination: 22% is excreted unchanged in the urine, the rest by biliary excretion and conversion to SN-38 toxicity: diarrhea- early onset within hours or during the infusion associated with cramping, vomiting, flushing and diaphoresis, controlled by atropine. late-onset diarrhea can occur later than 12 hours following drug administration, may be controlled by high-dose loperamide (an initial dose of 4 mg followed by 2 mg every 2 hours or 4 mg every 4 hours during the night)
Irinotecan
alopecia nausea and vomiting mucositis fatigue elevated liver function, caution in patients with liver dysfunction pulmanary toxicity (uncommon) associated with a reticulonodular infiltrate, fever, dyspnea, and eosinophilia
ANTIBIOTICS
Bleomycin, dactinomycin
Bleomycin
Oxidative cleavage of DNA initiated by hydrogen abstraction Metabolism: activated by microsomal reduction and degraded by hydrolase found in multiple tissues Elemination: renal 45-70% in first 24 hrs
Bleomycin
Reduce dose for creatinine clearance < 60 ml/min Toxicity: pulmonary interstitial infiltrates and fibrosis, increased risk in patients with underlying pulmonary disease, age > 70, renal insufficiency, prior chest radiation, oxygen during surgery, cisplatin desquamation, esp of fingers and elbows Reynaud phenomenon hypersensitivity reaction (fever, anaphylaxis, eosinophilic pulmonary infiltrates)
Dactinomycin (actinomycin D)
Inhibition of RNA and protein synthesis Elimination: renal 6-30%, bile 5-11% Avoid extravasation: necrosis Toxicity: myelosuppression nausea and vomiting mucositis diarrhea radiation sensitization and recall reactions
PROPHYLACTIC AGENTS
Antiemetic regimens:
Acute emesis: serotonin antagonist + dexamethasone or metoclopramide (1 mg/kg) + dexamethasone Delayed emesis: (cisplatin, carboplatin, doxorubicin, high dose cyclophosphamide): metoclopramide 0.5 mg/kg IV/PO QID x 24 d (8-16 doses) then every 4 hrs PRN Dexamethasone 4-8 mg IV/PO x 4 d Diphenhydramine 50 mg PO every 4 hrs, PRN only for restlessness or acute dystonic reactions
dexamethasone 20 mg PO 12 and 6 hrs prior to paclitaxel 20 mg IV 30-60 min prior to paclitaxel diphenhydramine 50 mg IV/PO 30-60 min prior to paclitaxel cimetidine 300 mg or ranitidine 50 mg IV 30-60 min prior to paclitaxel
Growth factors: G-CSF for prophylaxis in previous febrile neutropenia or high incidence of grade IV neutropenia
MESNA
derived in 1916 by Du Bois and Du Bois reduce the interpatient variability of drug exposure and, hence, drug effects
Pulmonary fibrosis Nausea/vomiting Diarrhea Cystitis Sterility Myalgia Neuropathy Local reaction Renal failure Myelosuppression Cardiotoxicity
Phlebitis
Infiltrating surrounding tissue blistering May be delayed 6-12 hr Severe necrosis Absent of blood return
Port-a-cath
Port inserted in vein for chemotherapy A Port B Catheter [tubing] C Subclavian vein D Superior Vena cava E Pulmonary vein F Aorta G Heart
Vestibular
Medulla oblongata
Vomiting center
Increased afferent input to the chemoreceptor trigger zone and vomiting center
Small intestine
Cell damage
CINV: Classification
Anticipatory
Acute
Delayed
Chemo
16 - 24 hours
Anticipatory
Delayed
Chemo
16 hours
24 hours
Acute CINV
Starts within the first 24 hours after chemotherapy administration
Pisters KMW, Kris MG. In: Principles and Practice of Supportive Oncology . Lippincott-Raven; 1998. Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer. Ann Oncol 1998;9:811819.
Berger AM et al. In: Cancer: Principles and Practice of Oncology. 6th ed. Lippincott Williams & Wilkins, 2001:28692880. Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer. Ann Oncol 1998;9:811819.
Time (Days)
Maximal emetic intensity seen within 24 hours postdose Distinct second phase seen, occurring on Days 2 5 postdose
Adapted from Tavorath R, Hesketh PJ Drugs 1996;52:639648. 1996. Used with permission from Adis International Limited.
12
24
120
Highly effective in acute vomiting, less effective for delayed events Optimal use is with dexamethasone
Berger AM et al. In: Cancer: Principles and Practice of Oncology. 6th ed. Lippincott Williams & Wilkins; 2001:28692880. Gralla RJ et al J Clin Oncol 1999;17:29712994. Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer. Ann Oncol 1998;9:811819. Endo T et al Toxicology 2000;153:189201. Hesketh PJ et al Eur J Cancer 2003;39:10741080.
MOA: Inhibition of 5-HT3 receptors on vagal afferent neurons in GI and in CTZ Efficacy improved when used with a steroid Well tolerated, minimal side effects
headache constipation bradycardia
Substance P
prototypic neuropeptide of the 50 known neuroactive molecules
now recognized as a member of the tachykinin family of neurotransmitters neurokinins are tachykinins found in mammals (substance P, NKA, NKB) 3 categories of NK receptors NK1 - affinity for substance P NK2 - affinity for NKA NK3 - affinity for NKB
CINV
CTZ Neurokinins: Substance P vestibular
GI
Cortical
Emetic Center
Nausea / Vomiting
CINV: Aprepitant
aprepitant (Emend, Merck & Co., Inc.) approved in the US in 2003 Mechanism of action:
selective, high affinity antagonist of human substance P at neurokinin 1 (NK1) receptors interferes with the substance P pathway that produces N/V no affinity for serotonin (5HT3), dopamine and corticosteroid receptors
Indication:
combination with other antiemetics indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy
Aprepitant Administration
Given for three days as part of a regimen that includes a 5-HT3 antagonist and a corticosteroid
Recommended dose
125 mg po 1 hour prior to chemotherapy 80 mg daily in the morning on days 2 and 3
CINV
CTZ Neurokinins: Substance P vestibular
GI
Cortical DA
5HT
Emetic Center
Nausea / Vomiting
Nausea:
Antiemetics Diet (avoid fried, fatty foods) Smaller meals
Diarrhea: Causes
Chemotherapy Infection Malabsorption Radiation induced Clostridium diffecile infection
Diarrhea
Chemotherapy induced
Supportive management
Medication management
Opioids
Loperamide (more effective) Diphenoxylate
Nephrotoxicity
Alkylating agents
Cisplatin Ifosfamide Carmustine Carboplatin
Antimetabolites
Methotrexate Gemcitabine
Other
Mitomycin C
Prevention of Nephrotoxicity
Cisplatin
Metrotrexate
Fractionate dose Continuous IV Adequate hydration Use mannitol (increase urine volume) Prevent dehydration Amifostine Carboplatin substitute (not for all case esp in germ cell tumor
Ifosfamide
Agents
Clinical presentation
Prevention
Treatment
CNS Toxicity
Agents
MTX (IT or IV) Cytarabine Ifosfamide L-asparaginase Cisplatin Lhermitts phenomena 5-FU Taxanes IFN alpha Vinca alkaloid (wrong route NEVER IT)
Neurotoxicity
High dose cytarabine ataxia L-asparaginase drowsiness, stupor Cisplatin ototoxic, ataxia Etoposide Vinca alkaloid jaw pain,cranial nerve pulsies Procarbazine Metrotrexate acute arachnoiditis Oxaliplatin sensory neurotoxic (cold trigger symptom parathesia
Peripheral Neuropathy
Sense of touch is distorted- ordinary touch can be unpleasant or painful. Burning or prickling feeling without stimulus Decreased touch sensation Difficulty sensing the position, location, orientation, and movement of the body and its parts (Proprioception) Important to report ANY of these symptoms to health care provider
Cardiotoxicity
Agents
Cumulative dose (> 450 mg/m2 in Thai) Dosing schedule Age (>65 or <4) HTX mediastinal irradiation Preexisting heart disease and arterial hypertension Diabetes Gender (female)
Pulmonary Toxicity
Risk factor
Cumulative dose: bleomycin busulfan carmustine, aldesleukin Age: bleomycin Radiotherapy: bleomycin busulfan, mitomycin, cyclophosphamide, doxorubicin, actinomycin Oxygen therapy: bleomycin, cyclophosphamide, mitomycin
Prevention
Treatment
Hand-Foot Syndrome
Description
Local cutaneous reaction after chemo. Seen on palms, finger, soles 2-12 days after chemo Tingling, burning of palms, hand, feet Pain, peeling Resolution in 7-14 days after stopping medication
Hand-Foot syndrome
Common in high dose therapy, prolonged infusion, liposomal forms Agents
Management
Stop dosing Topical wound care & cold cream base Pain management Steroid creams Pyridoxine Avoid heat and pressure
Hematologic complications
Febrile neutropenia Anemia Thrombocytopenia
Febrile neutropenia
Anemia Thrombocytopenia
Hb < 10 g/dL
Platelet transfusion
National Peer Reviews in Colorectal Cancer, Scientific Updates from the 30th annual ONS Meeting, Orlando, Fl. 2005
Stomatitis
Soft toothbrush Mild toothpaste Mild gargles Ice cubes Ibuprofen
Pain
Fatigue, GI upset, and psychosocial problems are often more prevalent, but pain is the #1 feared aspect of cancer for most patients
35% in lymphoma 56% in breast cancer 67% in head and neck cancer
Analgesia (pain relief) Activities of Daily Living (psychosocial functioning) Adverse effects (side effects)
Communicate
Intensity Location What the pain feels like What makes it worse What helps
Category Scale
Analgesic Classification
1.Opioids 1. weak/full agonist, partial agonist and mixed agonistantagonist (ceiling effect) 2. strong/full agonist (no ceiling effect no maximum dose) 2.NSAIDs (ceiling effect) good for bone pain 3.Adjuvant analgesic or coanalgesics 1.TCA (amitryptyline) for neuropathic pain 2.Antiepileptics (gabapentin, oxcarbazepine) for neuropathic pain 3.Steroids for cord compression 4.Bisphosphonates
Opioids
Constipation sennosides, bisacodyl, MgOH N/V ondansetron Respiratory depression (Naloxone) Sedation caffeine to resolve
Good treatments exist for nausea, sedation and a ground breaking treatment will soon be available for constipation
Pain Treatment
Morphine bolus or IM morphine When pain is relieved, off morphine oral weak opioids or NSAIDS
Chronic pain
Neuropathic pain
abnormal gastrointestinal functioning anorexia from nausea, anxiety, depression and cognitive dysfunction metabolic abnormalities caused principally by cytokines
(Keller, 1993)
Pharmacologic treatment of cachexia is targeted principally at anorexia and chronic nausea (Bruera, 1993)
Pharmacological Approaches
Corticosteroids Progestational agents (ie, megestrol acetate) Cannabinoids (ie, dronabinol) Antihistamines (ie, cyproheptadine) Unique agents (ie, hydrazine sulfate) Omega-3 fatty acids, EPA and docosahexaneoic acid (DHA) (n-3s) (Barber, et al, 2000; Hussey & Tisdale, 1999; Wigmore, et al, 2000)
Fatigue
Highly prevalent effecting 2/3s of patients Very disabling Also makes the job of caregiving more stressful and exhausting for family
Acneform Rash
Avoid sun, heat & humidity Use mild soaps Water based makeup is generally well tolerated Pharmacologic Mgmt. Topical and/or antibiotics Topical and/or oral antihistamines Cool compresses Petroleum jelly, silver sulfadiazine ointment for ulcerative lesions
Multiple white bands in the nails, representing periods of growth arrest, in this case due to cycles of treatment with 5-fluorouracil.
Oncologic Emergency
Oncologic Emergencies
Prevention (the best measure) Intravenous antibiotic therapy Anticoagulants, cryoprecipitated clotting factors
Early recognition and treatment Palliative High-dose corticosteroids High-dose radiation Surgery External back or neck braces to reduce pressure in the spinal cord
Hypercalcemia
Occurs most often in clients with bone metastasis Fatigue, loss of appetite, nausea and vomiting, constipation, polyuria, severe muscle weakness, loss of deep tendon reflexes, paralytic ileus, dehydration, electrocardiographic changes
(Continued)
Hypercalcemia (Continued)
(Continued)
Figure 1 Photographs of the patient showing the reduction in swelling of the face, neck and upper extremities
Chee CE et al. (2007) Superior vena cava syndrome: an increasingly frequent complication of cardiac procedures Nat Clin Pract Cardiovasc Med 4: 226230 doi:10.1038/ncpcardio0850
Late-stage signs include hemorrhage, cyanosis, change in mental status, decreased cardiac output, and hypotension.
Collaborative management includes high-dose radiation therapy, but surgery only rarely.
Conclusions
People with cancer are living longer The focus is on quality of life in addition to quantity People surviving cancer want to live normal lives People with cancer have multiple symptoms New treatments of various kinds are available and there is no need to suffer