Gastrointestinal Toxicity Of Chemotherapy

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Gastrointestinal ToxicityOfChemotherapy
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• Chemotherapeutic agents have narrow therapeutic
  index and do not discriminate between normal and
  target cells???
• Bone Marrow, spermatogonia, GI cells

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Nausea and Vomiting

• Most common toxicity
• Mediated through the Chemoreceptor trigger zone.
• Occurs 3-6 hours post administration and subsides
  after 36-48 hours.
• Most common agents Cisplatinum,
  DTIC,Cyclophosphamide, VP-16, BCNU.

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• Emetogenic injury to the gastric mucosa
• and the gastroesophageal junction (Mallory-Weiss
  tear) commonly occur and produce upper
  gastrointestinal bleeding.
• These injuries can produce very significant
  bleeding in the setting of thrombocytopenia.

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Treatment

• Metoclopromide( High dose)
• Dexamethasone
• Serotonin antagonist

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Mucositis

• Methotrexate, Fluorouracile,Actinomycin-D,
  Doxorubicin, Bleomycin, Vinblastin
• Enhanced with Radiation
• Prevented with Leucovorin if MTX is used

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• Preclude oral intake ? Malnutrition
• Pain
• Infection

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• When esophagitis is suspected,endoscopy is the
  preferred diagnostic procedure and allows the
  early administration of appropriate therapy.
• In addition to visual inspection,endoscopic
  brushings and biopsies can be obtained for
  microscopic examination, special stains, and
  culture.
• Double-contrast esophagography will reveal
  evidence of esophagitis in severe cases, but
  sensitivity and specificity are limited.

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Treatment

• Conservative and symptomatic
• Warm saline mouth wash
• Topical anesthetics before ingestion
• Nystatin
• Fluid intake with straw and IV nutritional support

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Pseudomenbranous Colitis

• Clostridium difficile is the most common
  bacterial cause of infectious diarrhea in
  antibiotic-treated patients and in those
  undergoing cancer chemotherapy.

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TYPHLITIS

• Typhlitis refers to a clinical syndrome of fever
  and right-lowerquadrant tenderness in a
  neutropenic patient after cytotoxic chemotherapy.
• Typhlitis (from the Greek word typhlon, meaning
  cecum)
• Typhlitis appears to be more common among
  children than adults.

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CHEMOTHERAPY-RELATED ILEUS

• Vincristine treatment is associated with adynamic
  ileus and has been implicated in some cases of
  cecal perforation.
• Although the etiology of vincristine-induced
  ileus is not known, improvement has been reported
  with the use of metoclopramide.

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• Cisapride may also be beneficial in that this
  agent improves motility throughout the intestinal
  tract whereas metachlopramides effect is limited
  to the upper gastrointestinal

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DIARRHEA

• 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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5FU

• The toxic effects of 5-FU have been
• shown to depend upon age and sex, being more
  common in women than men and worse in women over
  age 70.

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CPT-11

• A hyperacute diarrhea with abdominal cramping
  appears to be mediated by a cholingeric effect
  and can be effectively treated with atropine as
  well as loperamide.
• The delayed (more than 24 hours post infusion)
  type of diarrhea induced by this agent correlates
  with the peak plasma concentration of the
  metabolite 7-ethyl-10-hydroxycamptothecin
  (SN-38).

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• Irinotecan induced diarrhea can be severe, and
  more than 18 of patients treated with this agent
  require hospitalization
• Early and aggressive antidiarrheal therapy with
  loperamide and/or diphenoxylate can significantly
  reduce the proportion of patients developing
  uncontrolled diarrhea and its complications of
  dehydration and electrolyte imbalance.

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ACUTE PANCREATITIS

• Acute pancreatitis may occur secondary to
  medications
• such as metronidazole, cortiosteroids, and
  furosemide.
• During the course of chemotherapy, pancreatitis
  has been reported with azathioprine,ifosfamide,pre
  dnisone,L-asparaginase,cytosine ,arabinoside, and
  various regimens of combination chemotherapy
  including Vinca alkaloids, methotrexate,
  mitomycin C, 5-FU,
• cyclophosphamide, cisplatin, and bleomycin