Side Effect of Chemotherapy

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Side Effect of Chemotherapy

• ??. ?????? ????????? B.Pharm, M.Sc.
  (Pharmacology)
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Alkylating agents

• Alkylating agents are the oldest and most
  commonly used class of chemotherapy drugs, and
  work by directly damaging DNA and preventing
  cancer cells from reproducing.
• Some examples of alkylating agents are
  carboplatin, cisplatin, cyclophosphamide and
  oxaliplatin.

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Antimetabolites (Structural Analogs)

• Antimetabolites are chemotherapy drugs that
  interfere with DNA and RNA growth.
• Some examples of antimetabolites are
  capecitabine, gemcitabine, fludarabine,
  cytarabine, methotrexate and pemetrexed (Alimta).

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Antibiotics

• Many of these antibiotics bind to DNA through
  intercalation between specific bases and block
  the synthesis of new RNA or DNA (or both), cause
  DNA strand scission, and interfere with cell
  replication.
• Some examples of antibiotics are anthracyclines
  (doxorubicin), bleomycin and mitomycin-C

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Plant Alkaloids

• Plant alkaloids are derived from certain types of
  plants found in nature, and inhibit or prevent
  mitosis or inhibit enzymes from making proteins
  necessary for cell reproduction.
• Some examples of plant alkaloids are the taxanes,
  docetaxel, paclitaxel, and the vinca alkaloids
  (vinblastine, vincristine, vinorelbine).

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Monoclonal antibodies

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  antibody ???????????????????????????? Non-Hodgkin
  lymphoma
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  Herceptin (Trastuzumab ?????? breast tumor
  overexpressing human epidermal growth factor
  receptor 2) Campath (Alemtuzumab ?????? B cell
  chronic lymphocytic leukemia)

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Monoclonal antibodies
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Cardiovascular

• Anthracyclines (doxorubicin)
• Acute and subacute cardiac toxicity
• which occur immediately after a single dose
  of an anthracycline or a course of anthracycline
  therapy, are uncommon under current treatment
  protocols. Several distinct, early cardiotoxic
  effects of anthracyclines have been described.
• Electrophysiologic abnormalities
• Sinus tachycardia is the most common rhythm
  disturbance

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Cardiovascular

• Anthracyclines (doxorubicin)
• Chronic Cardiotoxicity
• The incidence of congestive heart failure
  secondary to doxorubicin-induced cardiomyopathy
  depends on the cumulative dose of the drug.
• At total doses of less than 400 mg/m2 body
  surface area, the incidence of congestive heart
  failure is 0.14 this incidence increases to 7
  at a dose of 550 mg/m2 body surface area and to
  18 at a dose of 700 mg/m2 body surface area

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Cardiovascular

• 5-Fluorouracil, Cyclophosphamide and taxanes
• Combination with Anthracyclines breast cancer
  monitor cardiac function
• Women with Her-2 receptor positive- receive
  Herceptin (trastuzumab) cardiotoxicity
• Cardiac toxicity of doxorubicin is aggravated by
  the anti-HER-2 antibody Trastuzumab or by the
  tubulin-active taxane

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Cardiovascular

• Pegylated liposomal doxorubicin (PLD) is equally
  active but associated with a significantly lower
  risk of cardiotoxicity compared with conventional
  doxorubicin whether administered as monotherapy
  or in combination with trastuzumab

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Cardiovascular

• Regular left-ventricular function monitoring
  before and during therapy is mandatory in all
  patients receiving adjuvant trastuzumab after
  anthracyclines

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Cardiovascular

• Trastuzumab in combination with non-anthracycline
  chemotherapy does not seem to be associated with
  any increased risk of cardiotoxicity
• The optimal duration for adjuvant trastuzumab
  therapy suggested by current data is 1 year,
  although some data support as little as 9 weeks
  of trastuzumab however, scheduling trastuzumab
  before initiating adjuvant anthracycline therapy
  remains experimental and might be risky because
  of the long half-life of trastuzumab

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Cardiovascular

• Trastuzumab - half-lives of 2.7, 3.1, 8.8, and
  10.4 days were reported after single doses of 1,
  2, 4, and 8 mg/kg, respectively

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Cardiovascular

• Epirubicin (Ellence, Pharmorubicin)
• Cumulative dose thresholds are usually set at 450
  mg/m2 for doxorubicin and 750 mg/m2 for
  epirubicin, though close monitoring is
  recommended when more than 300 mg/m2 of
  doxorubicin and 600 mg/m2 of epirubicin are
  given.
• The risk of epirubicin cardiotoxicity was found
  to be considerable at doses above 1000 mg/m2

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Cardiovascular

• Epirubicin (Ellence, Pharmorubicin)
• Epirubicin (Ellence, Pharmorubicin), which has
  been developed as a semi-synthetic derivate of
  doxorubicin, is characterised by faster
  elimination and reduced toxicity.

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Cardiovascular

• Taxanes
• Taxanes (paclitaxel, Taxol docetaxel, Taxotere)
• The principal mechanism of these drugs is the
  inhibition of the microtubule function
• Treatment of several solid tumours like breast
  cancer, ovarian cancer and non-small-cell lung
  cancer

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Cardiovascular

• Taxanes
• Though as single agents the taxanes have
  negligible cardiac toxicity, it has been shown
  that when paclitaxel is used in combination with
  doxorubicin the incidence of CHF is increased to
  more than 20

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Respiratory

• Pulmonary toxicity is a serious potential
  complication of the use of cytotoxic drugs that
  can be debilitating and life threatening.
• Rapid recognition of this problem and its
  management are critical if morbidity is to be
  limited.

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Respiratory

• BLEOMYCIN-INDUCED INTERSTITIAL PNEUMONITIS
• Bleomycin is a antibiotic originally discovered
  in 1966 by
• Standard therapy for treatment of germ cell
  tumours, often in combination with platinum and
  etoposide.
• Bleomycin has long been known to cause
  interstitial pneumonitis (BIP) and this is the
  most thoroughly studied form of
  chemotherapy-induced lung toxicity.
• The incidence of BIP is 10, with a fatality rate
  of between 1 and 2

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Respiratory

• GEMCITABINE-ASSOCIATED PULMONARY TOXICITY
• Gemcitabine, a pyrimidine analogue of
  deoxycytidine, is widely used in the treatment of
  both haematological and solid malignancies
  including non-small cell lung, pancreatic and
  ovarian cancers.
• Gemcitabine is associated an uncommon but serious
  interstitial pneumonitis that has been associated
  with fatality, and which develops rapidly within
  72 hours.
• The incidence has been estimated at between 0.02
  and 0.06

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Respiratory

• Gemcitabine is commonly prescribed in a plat-
• inum-based doublet for the treatment of non-
• small cell lung cancer platinum resistance may
• be common, and there is currently interest in
• exploring the efficacy of non-platinum contain-
• ing combinations in this malignancy.
• Use of a combination of docetaxel and gemcitabine
  has been explored in a weekly schedule, but is
  associated with significant pulmonary toxicity.

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Respiratory

• Irinotecan is a topoisomerase 1 inhibitor used
  extensively for the treatment of metastatic colon
  cancer, which has been linked to pulmonary
  toxicity.
• In early clinical studies in Japan, progressive
  deterioration followed by death was typical, with
  no response to corticosteroids.
• In American studies with irinotecan Pre-existing
  pulmonary dysfunction may predispose to
  irinotecan-induced lung injury.

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Respiratory

• Dyspnoea and cough have been described in 20 of
  patients

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Gastrointestinal

• Mucositis
• Oro-pharyngeal mucositis may follow radiotherapy,
  chemotherapy or haemopoetic stem cell transplant
  and effects approximately 3050 of these patient
  populations.

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Gastrointestinal

• Mucositis
• Chemotherapy induced damage to the mucous
  membranes of the body occurs because of the
  relatively high turnover of cells in these
  tissues compared with others and results in local
  in?ammation, cellular apoptosis and ulceration of
  the membrane with loss of barrier function and
  opportunistic secondary infection especially with
  candida and herpes simplex virus.

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Gastrointestinal

• Mucositis
• Patients with poor dental hygiene or caries and
  gum disease pre-chemotherapy should be referred
  to dental hygienist and dental surgeon for urgent
  care at least 10 days before chemotherapy
  commences to diminish their increased risk of
  infective complications both locally and
  systematically.

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Gastrointestinal

• Mucositis
• The mouth is often the source of sepsis in
  febrile neutropenic episodes.

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Gastrointestinal

• Mucositis
• Anthracyclines and taxanes are other important
  chemotherapeutic drugs that cause mucositis.

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Gastrointestinal

• Mucositis
• World Health Organization Grading of
  Mucositis/Stomatitis
• Grade (Symptoms)
• 0 None
• I Painless ulcers, erythema, or mild soreness
• II Painful erythema, edema, or ulcers, but can
  eat
• III Painful erythema, edema, or ulcers, but
  cannot eat
• IV Requires parental or enteral support

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Gastrointestinal

• Mucositis
• Prophylactic chlorhexidine and nystatin or
  clotrimazole may be given to reduce the risk of
  indirect mucotoxicity from bacteria and fungi in
  patients at high risk for greater than grade 2 or
  prolonged toxicity.

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Gastrointestinal

• Mucositis
• Prophylactic fluconazole reduces the risk of
  oropharyngeal candidiasis at the risk of the
  development of resistance.

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Gastrointestinal

• Mucositis
• Herpes simplex virus-antibody-positive patients
  undergoing high-dose chemotherapy with stem cell
  rescue should be given acyclovir 250 mg/m2
  intravenously every eight hours for prevention of
  mucocutaneous infections from viral reactivation.

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Gastrointestinal

• Xerostomia (dry mount)
• A variety of drugs other than chemotherapeutics
  are prescribed for cancer patients like
  sedatives, opiates, antidepressants,
  antihistamines, diuretics which may also cause
  xerostomia.

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Gastrointestinal

• Nausea and vomiting
• Nausea and vomiting can be triggered by
  activation of the chemoreceptor trigger zone or
  via afferent inputs to the vomiting centre of the
  brain in the nucleus tractus solitarius, which
  receives inputs from the GI tract via the vagus
  nerve

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Gastrointestinal

• Today's studies on receptors found in the
  chemoreceptor trigger zone (CTZ), e.g., dopamine,
  serotonin, and neurokinin, have made great
  advances for patients prone to emesis during
  chemotherapy treatment.

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Gastrointestinal

• Emetic classifications
• The American Society of Clinical Oncology (ASCO)
  has developed a rating system for
  chemotherapeutic agents and their respective risk
  of acute and delayed emesis.

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Gastrointestinal

• Acute nausea and vomiting
• Nausea and vomiting that occurs within 24 hours
  of administration of chemotherapy is termed acute
  nausea and vomiting.
• The chances of developing acute nausea and
  vomiting depend on the drugs that are being used
  in chemotherapy regimens.

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Gastrointestinal

• Nausea and vomiting
• Emetic classifications. The American Society of
  Clinical Oncology (ASCO) has developed a rating
  system for chemotherapeutic agents and their
  respective risk of acute and delayed emesis.
• High risk Emesis that has been documented to
  occur in more than 90 of patients
• cisplatin (Platinol)
• mechlorethamine (Mustargen)
• streptozotocin (Zanosar)
• cyclophosphamide (Cytoxan), 1,500 mg/m2 or more
• carmustine (BiCNU)
• dacarbazine (DTIC-Dome)
• dactinomycin

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Gastrointestinal

• Nausea and vomiting
• Moderate risk of nausea and vomiting Vomiting
  occurs in 30 to 90 of patients treated with
  these drugs
• carboplatin (Paraplatin)
• cyclophosphamide (Cytoxan), less than 1,500 mg/m2
• daunorubicin (DaunoXome)
• doxorubicin (Adriamycin)
• epirubicin (Pharmorubicin)
• idarubicin (Idamycin)
• oxaliplatin (Eloxatin)
• cytarabine (Cytosar), more than 1 g/m2
• ifosfamide (Ifex)
• irinotecan (Campto)

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Gastrointestinal

• Nausea and vomiting
• Low risk of nausea and vomiting Vomiting occurs
  in 10 to 30 of patients treated with these
  drugs
• mitoxantrone (Novantrone)
• paclitaxel (Taxol)
• docetaxel (Taxotere)
• mitomycin (Mutamycin)
• topotecan (Hycamtin)
• gemcitabine (Gemzar)
• etoposide (Vepesid)
• pemetrexed (Alimta)
• methotrexate (Rheumatrex)
• cytarabine (Cytosar), less than 1,000 mg/m2
• fluorouracil (Efudex)
• bortezomib (Velcade)
• cetuximab (Erbitux)
• trastuzumab (Herceptin)

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Gastrointestinal

• Nausea and vomiting
• Minimal risk of nausea and vomiting Vomiting
  occurs in fewer than 10 of patients
• vinorelbine (Navelbine)
• bevacizumab (Avastin)
• rituximab (Rituxan)
• bleomycin (Blenoxane)
• vinblastine (Velban)
• vincristine (Oncovin)
• busulphan (Myleran)
• fludarabine (Fludara)
• 2-chlorodeoxyadenosine (Leustatin)

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Gastrointestinal

• Delayed (or late) nausea and vomiting
• Nausea and vomiting that occurs more than 24
  hours after chemotherapy administration is
  considered delayed, or late, nausea and vomiting.
  
• Delayed nausea and vomiting is associated more
  commonly with certain chemotherapy drugs like
  cisplatin and cyclophosphamide.
• In lymphomas some other drugs like doxorubicin
  and ifosfamide may also cause delayed nausea and
  vomiting

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High-Risk Guidelines (gt90)

• Acute Emesis (0 to 24 hours after
  chemotherapy)5-HT serotonin receptor
  antagonists, corticosteroids (dexamethasone), and
  aprepitant are all effective in the acute
  treatment of emetic symptoms related to
  chemotherapy.
• Delayed Emesis (gt24 hours after chemotherapy)
  Recommendations for the prevention of delayed
  emesis in oncology patients receiving cisplatin
  and other agents of high emetic risk include the
  use of dexamethasone and aprepitant.

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Moderate-Risk Guidelines (30 to 90)

• Acute Emesis recommends a three-drug
  combination-a 5-HT3 serotonin receptor
  antagonist, dexamethasone, and aprepitant-for all
  patients receiving anthracycline and
  cyclophosphamide (AC).
• For patients who receive an antineoplastic agent
  of moderate emetic risk other than AC, ASCO
  recommends a two-drug combination a 5-HT3
  serotonin receptor antagonist and dexamethasone.

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Moderate-Risk Guidelines (30 to 90)

• Delayed Emesis For patients who receive AC
  therapy, single-agent aprepitant should be used
  to prevent delayed-onset emesis
• Dexamethasone as a single agent or a 5-HT3
  serotonin receptor antagonist is preferred for
  delayed emesis regarding all other agents of
  moderate emetic risk.

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Low-Risk Guidelines (10 to 30)

• Acute Emesis The 1999 guidelines recommended no
  antiemetic agent for the prevention and/or
  treatment of chemotherapy-induced emesis.
• However, the updated recommendations advise 8 mg
  of dexamethasone for the treatment of patients at
  low emetic risk.
• Delayed Emesis Preventive use of antiemetic
  agents for delayed emesis is discouraged in
  patients who receive low-risk chemotherapy.

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Minimal-Risk Guidelines (lt10)

• Acute and Delayed Emesis
• This risk category is a new addition in the 2006
  antiemetic guidelines a number of agents in this
  category were considered low risk in 1999.
• Bleomycin, 2-chlorodeoxyadenosine, fludarabine,
  vinblastine, and vincristine are among the
  chemotherapy agents that are now categorized as
  minimal risk.

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Minimal-Risk Guidelines (lt10)

• Depending on the patient and history of poor
  emetic control with these agents, a small
  percentage of patients may require pretreatment
  with antiemetics.
• In these rare cases, a one-time dose of
  dexamethasone 8 mg, phenothiazine, or
  metoclopramide (as needed) is common.

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Gastrointestinal

• Nausea and Vomiting
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• Anthracyclines Adriamycin, Epirubicin
• Taxanes Paclitaxel,Docetaxel
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Gastrointestinal

• Diarrhoea is a common ?nding with many different
  forms of chemotherapy, but especially
  anti-metabolites such as ?uorouracil and
  methotrexate, irinotecan and the alkylating
  agent cisplatin.
• Mucosal damage by cytotoxic agents produces net
  fluid secretion by the intestine and damage to
  intestinal villi with a loss of absorptive
  capacity 5-fluorouracil (5-FU),cisplatin,and
  irinotecan

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Gastrointestinal

• Diarrhoea
• Irinotecan is a relatively new chemotherapeutic
  agent used to treat a variety of solid tumours.
  Its main action on malignant cells is by
  inhibiting DNA topoisomerase I.

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Gastrointestinal

• Diarrhoea
• Major side-effects of irinotecan use are severe
  diarrhoea and leukopenia, which severely limit
  the dose of administered drug.
• Irinotecan causes diarrhoea in approximately
  6080 of patients, with two distinct types of
  diarrhoea recognised.

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Gastrointestinal

• Diarrhoea
• National Cancer Institute Common Toxicity
  Criteria for Diarrhoea
• Grade 0 Increase of less than 4 stools/day over
  baseline
• Grade 1 Increase of 4-6 stools/day over baseline
• Grade 2 Increase of greater than 7 stools/day
  over baseline, incontinence
• Grade 3 Life-threatening consequences including
  extremely low blood pressure as a result of
  s evere dehydration
• Grade 4 Death

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Gastrointestinal

• Diarrhoea
• Grade 3 is reached if there is a need for
  parenteral ?uids and Grade 4 the need for
  critical care admission

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Gastrointestinal

• Diarrhoea
• Management of diarrhoea includes adequate
  rehydration and electrolyte replacement (orally
  wherever possible) and once infective causes have
  been ruled out the use of high-dose loperamide, 4
  mg starting dose then 2 mg after every bowel
  motion up to 2-hourly, is indicated.
• If this fails, consideration of octreotide 100 mg
  s.c. three times daily increasing if required to
  2500 mcg three times daily is indicated.

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Gastrointestinal

• Diarrhoea
• In the future use of epithelial growth factors
  may develop as these are showing some bene?ts in
  animal studies.

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Gastrointestinal

• Constipation
• Constipation usually results from the use of
  opioid analgesics, anti-emetics of the 5-HT3
  family and as a direct hypo-motility effect of
  vinca alkaloids on the gut.
• The vinca alkaloids may also cause a (usually)
  temporary neuropathic ileus.

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Gastrointestinal

• Colitis
• Colitis can result from a variety of infective
  and drug-induced mechanisms.

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Gastrointestinal

• Neutropenic colitis
• Based on the occurrence of 3 or more of the
  following signs fever, pronounced watery
  diarrhea (5 stools per day), abdominal
  distention and/or tenderness with rebound, bloody
  stools, or frank peritoneal signs.

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Gastrointestinal

• It is believed that a combination of
  chemotherapy-induced mucosal injury and
  immunosuppression allows local microbial invasion
  and damage in the bowel wall.
• This may lead to infarction, necrosis,
  haemorrhage, perforation or a localised colitis.

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Gastrointestinal

• The management is individualised to the patient
  and tends to start with conservative therapy with
  rest of the gastrointestinal tract,
  broad-spectrum antibiotic and anti-fungal cover
  and support of the bone marrow with GCSF.

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Gastrointestinal

• Infective colitis CMV colitis may occur in
  patients receiving immunosuppressive chemotherapy
  and particularly is found in patients following
  allogeneic stem cell or bone marrow transplant
  with on-going immunosuppressive therapy.
• Over 90 of infections affect the large bowel and
  less than 10 the small bowel.

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Gastrointestinal

• Haemorrhage, mucosal ulceration and perforation
  are all associated.
• Treatment is with gangciclovir or foscarnet.
• Intravenous immunoglobulin (IVIg) may have a role
  too

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Gastrointestinal

• Clostridium dif?cile colitis
• Clinical symptoms of C difficile disease vary
  widely from mild diarrhea to severe abdominal
  pain accompanied by fever (typically gt101F) and
  severe weakness.
• Occur either as a result of antibiotic use in
  patients with other infective complications
  following chemotherapy or may occur de novo in
  antibiotic patients following the use of
  chemotherapy only.
• Paclitaxel has been implicated as having a higher
  risk of this complication than other agents.

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Gastrointestinal

• Perforation of the bowel
• Perforation of the bowel In addition to bowel
  perforation associated with colitis, the
  chemotherapeutic human recombinant monoclonal
  antibody Bevacizumab (Avastin) that binds to
  vascular endothelial growth factor has been
  associated with bowel perforation de novo.

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Gastrointestinal
Perforation of the bowel
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Hepatic

• Hepatic impairment
• Dysfunction secondary to haemopoietic stem cell
  transplantation is commoner but not always
  attributable to the chemotherapeutic regimen.

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Hepatic

• Hepatic impairment
• Care must be taken to consider the dosing of
  chemotherapy in patients with known hepatic
  impairment as the metabolism and pharmacokinetics
  of these agents may be altered and systemic
  toxicity result e.g. doxorubicin is largely
  eliminated in the bile and cholestasis results in
  elevation of plasma concentrations.
• In general, if a signi?cant and sustained
  alteration of liver function is noted following
  the introduction of a chemotherapeutic agent and
  it reverses on withdrawal of the agent, the agent
  should be substituted by another for the next
  cycle of chemotherapy.

84
Renal impairment secondary to chemotherapy

• Many chemotherapeutic agents or their active
  metabolites undergo renal elimination and
  chemotherapy-associated diseases of glomeruli,
  tubules, renal interstitium and renal
  micro-vasculature are recognised.
• Effects of chemotherapy can also manifest in the
  bladder with haemorrhagic cystitis, a common side
  effect with alkylating agents.

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Renal impairment secondary to chemotherapy

• Additionally, patients also frequently receive
  other nephrotoxic drugs concomitantly such as
  aminoglycoside antibiotics, vancomycin,
  foscarnet, amphotericin, NSAIDs and these may
  further damage the kidney.

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Renal impairment secondary to chemotherapy

• As changing renal function will alter the
  elimination of many agents and their potential
  for systemic toxicity, regular assessment of
  renal function should be undertaken during the
  planned chemotherapy administration period this
  can be done measuring plasma urea and
  electrolytes as well as urinary creatinine
  clearance and electrolytes.

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Renal impairment secondary to chemotherapy

• As different members or the same class of drugs
  affect the kidney differently, it may be
  necessary to alter the chemotherapy regime
  altogether with time.
• The platinum-based agent cisplatin is highly
  nephrotoxic causing direct tubular damage,
  interstitial damage and results in renal tubular
  acidosis, acute tubular necrosis and chronic
  renal impairment.
• By contrast carboplatin is less nephrotoxic
  causing a (usually) reversible tubular injury and
  oxaliplatin is less nephrotoxic still being safe
  to use in patients even when moderate renal
  impairment antecedes chemotherapy.

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Neurological

• Central and peripheral nervous system injuries
  and syndromes can result as a direct or indirect
  effect of chemotherapy and can cause confusion
  with alternative tumour-related diagnoses such as
  cerebral metastatic disease, spinal cord
  compression, paraneoplastic syndromes or
  co-incidental disease such as infective
  meningitis and primary epilepsy.

89
Neurological

• Some chemotherapeutic agents such as methotrexate
  may be administered intrathecally and
  differentiation of complications of the therapy
  as opposed to complications of the procedure
  (infective meningitis/encephalitis, spinal cord
  trauma, neuropraxia) is desirable.

90
Neurological

• Peripheral neurological injuries Peripheral
  sensory and motor neuropathies are
  well-recognised side effects of taxanes, vinca
  alkaloids and nucleoside analogues.

91
Neurological

• Central neurological injuries As well as
  permanent leucoencephalopathy, transient aseptic
  meningitis and transverse myelitis seen with
  intrathecal methotrexate, acute and subacute
  encephalopathies can develop resulting in
  confusion, seizures, focal neurological de?cits
  and amnesia several days after therapy.

92
Bone marrow suppression and immune de?ciency

• Bone marrow suppression and immune de?ciency - a
  drop in the immunocyte, platelet and red cell
  count in the body merely re?ects a side effect of
  treatment in that as well as leading to death

93
Bone marrow suppression and immune de?ciency

• Low platelets
• easy bruising
• bleeding nose bleeds, gums, or mouth
• tiny red spots on the skin (petechiae)
• blood in the urine
• dark or black bowel movements

94
Bone marrow suppression and immune de?ciency

• Low white blood cells
• fever and chills
• rash
• diarrhea
• signs of infection (anywhere in the body)
• swelling
• redness
• an area that is warm to touch

95
Bone marrow suppression and immune de?ciency

• Low red blood cells
• fatigue
• paleness of skin, lips, and nail beds
• increased heart rate
• tires easily with exertion
• dizziness
• shortness of breath

96
Bone marrow suppression and immune de?ciency

• Immunomodulatory agents such as rituximab and
  alemtuzumab are, respectively, directed against
  CD20 and CD52 epitopes on white cells and used
  primarily to treat lymphoid cancers.
• Alemtuzumab is particularly highly
  immunosuppressive and despite recovery of the
  overall white cell count, clinical
  immunosuppression may continue for years
  following treatment.
• In addition to lymphopenia, both may also cause
  hypogammaglobulinaemia.
• In such instances, there is an evidence that
  administration of immunoglobulin may aid
  resolution of sepsis.

97
Rituximab and Alemtuzumab
98
Tumour lysis syndrome

• ??????????????????????????????????????????????????
  ????????????????
• ??????????????????????????????????????????? ????
  ???????????
• ??????????????????????????? ??????????????????????
  ??????????????
• ????? ????????????????????????????

99
Tumour lysis syndrome

• 1. ?????????????????????????? ????????????????????
  
• ?????????? ????????????????????? ???? ?????????
  ????????
• ??????? ?????????? ??????????????? ??????????
  ??????? ????
• ???????????????????????????????? ??????
  ??????????????????????
• ????????????????????????????????? 6-72 ???????
  ?????????????
• ?????

100
Tumour lysis syndrome

• 2. ???????????????????????????????????????????
• ??????????????????????? ??????????????? ???
  ??????????????????
• ???????????????????????????????????????? ???????
• ?????????? 24-48 ??????? ??????????????????

101
Tumour lysis syndrome

• 3. ???????????????????????
• ??????????????????????????????? ????????????????
  ???????????????? ??????
• ?????? ?????????????????????? ????????????????????
  ?????????
• ????????????????????????????????????? 1
  ??????????????? ??????
• ???????????????????? ????????????????????????
  0.6-0.75
• ?????????????????????????????????
  ??????????????????????
• ??????????????????????? 24-48 ???????
  ??????????????????

102
Tumour lysis syndrome

• ?????????????????????????????????? TLS ??????
  cisplatin, etoposide,
• fludarabine, intrathecal methotrexate, ???
• paclitaxel

103
Tumour lysis syndrome
104
Hypersensitivity reactions

• Recognised in association with the administration
  of chemotherapeutic agents especially when
  administered intravenously.
• These range from mild fever seen with over 50 of
  bleomycin administrations to fulminant
  anaphylaxis.
• The commonest causative agents of severe
  reactions are monoclonal antibodies such as
  rituximab and Herceptin but they occur frequently
  with agents such as asparaginase, carboplatin and
  etoposide too and infrequently with nearly all
  other chemotherapeutic drugs.

105
Hypersensitivity reactions

• Reactions are usually anaphylactic (type I) or
  anaphylactoid, but type IIIV hypersensitivity
  reactions occur too.

106
Hypersensitivity reactions

• There are four different types of
  hypersensitivities that result from different
  responses of the immune system
• Type I Immediate hypersensitivity
• - onset within minutes of antigen challenge
• - examples are allergies to molds, insect bites
  
• Type II Cytotoxic hypersensitivity
• - onset within minutes or a few hours of
  antigen challenge
• - examples are adult hemolytic anemia and drug
  allergies
• Type III Immune complex-mediated
  hypersensitivity
• - onset usually within 2-6 hours
• - examples include serum sickness and systemic
  lupus
• erythematosus
• Type IV Delayed Hypersensitivity
• - inflammation by 2-6 hours peaks by 24-48
  hours
• - examples include poison ivy and chronic
  asthma

107
Type I Immediate hypersensitivity
108
Hypersensitivity reactions

• Proper type IgE-mediated reactions generally
  require cessation of the agent while many of the
  other reactions can be dealt with by slowing the
  rate of infusion and pre-treatment with
  antihistamines and steroids.
• Certain medications such as bleomycin come with
  clear guidelines on administration of tiny test
  doses several hours before the main drug infusion
  is commenced.

109
Hypersensitivity reactions

• Additionally, precautions such as the concomitant
  administration of paracetamol as an antipyretic
  are often written into individual unit protocols.

110
Conclusion

• To effectively manage these patients care, it is
  important to be aware of both the short-and
  long-term side effects of chemotherapeutic
  agents, and to understand the physiological
  changes that may occur during the course of their
  treatment.