Palliation of Chemotherapy Associated Nausea

1
Palliation of Chemotherapy- Associated Nausea
Vomiting

• Erin McBride M3
• May 2006

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Chemo-Associated N/V

• Acute nausea and vomiting - Initial 24 hours
  after chemotherapy.
• Delayed nausea and vomiting - Later than 24 hours
  after chemotherapy.
• Anticipatory nausea and vomiting -Days to hours
  before chemotherapy.

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Pathogenesis
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Emetogenicity of Chemotherapeutic Agents

• High (gt90)
• cisplatin, dacarbazine, procarbazine, high dose
  cyclophosphamide, carmustine
• Moderate (30-90)
• Carboplatin, Ifosfamide, Cyclophosphamide,
  Doxorubicin, Epirubicin, Daunorubicin
• Low (10-30)
• Topotecan, Gemcitabine, Paclitaxel, Etoposide,
  Methotrexate, Mitomycin, Fluorouracil,
  Trastuzumab
• Minimal(lt10)
• Bleomycin, Busulfan, Vincristine,
  Vinblastine,Chlorambucil, Hydroxyurea,
  Methotrexate

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Antiemetic Agents

• Dopamine (DA) Antagonists
• Reglan (metoclopramide)
• Phenergan (promethazine)
• Compazine (prochlorperazine)
• Serotonin (5HT-3) Antagonists
• Zofran (ondansetron)
• Kytril (granisetron)
• Anzemet (dolasetron)
• Aloxi (palonosetron) - IV only
• Protachykinin-1 (NK-1) Antagonists
• Emend (aprepitant)
• Corticosteroids
• Cannabinoids
• Marinol (delta-9-THC)

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Dopamine Antagonists

• MOA antagonize the D2 receptors in the
  chemoreceptor trigger zone (CTZ) in the
  brainstem, blocking nausea and vomiting also
  prokinetic to GI tract
• Useful for adjuvant to other agents in
  refractory N/V gastroparesis
• SE extrapyramidal effects

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Serotonin Antagonists

• MOASerotonin receptors of the 5-HT3 type are
  present both peripherally on vagal nerve
  terminals and centrally in the CTZ. It is not
  certain whether antiemetic action is mediated
  centrally, peripherally, or in both sites.
• Useful for primary prophylaxis/palliation of
  chemo-induced N/V
• SE anaphylaxis

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Protachykinin-1 Antagonists

• MOA blocks CNS substance P/neurokinin 1
  receptors (centrally mediated)
• Useful for delayed acute chemo-associated N/V
• SE neutropenia

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Corticosteroids

• MOA unknown
• Useful for adjuvant with 5HT3 antagonists and
  NK-1 antagonists, primary prophylaxis for
  low/moderate emetogenicity agents
• SE adrenal insufficiency, psychosis,
  immunosuppression, osteoporosis, PUD, CHF,
  anaphylaxis

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Cannabinoids

• MOA stimulate cannabinoid (CB1) receptors,
  inhibiting 5HT centrally peripherally
• Useful for chemo post-op associated N/V,
  chronic pain, cachexia
• SE dizziness, euphoria, paranoia

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Things To Think About

• Prophylaxis is better than treatment
• Combinations may work when single drug doesnt
• These drugs are expensive!
• Unfortunately, there is still a high failure
  ratethere is more research to be done

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References

• Dahlin C Lynch M Szmuilowicz E. Management of
  Symptoms Other than Pain. Anesthesiology Clin N
  Am, 24 (2006) 39 60.
• Darmani NA Johnson JC. Central and peripheral
  mechanisms contribute to the antiemetic actions
  of delta-9-tetrahydrocannabinol against
  5-hydroxytryptophan-induced emesis. Eur J
  Pharmacol, 19-MAR-2004 488(1-3) 201-12
• Clarke SJ Sharma R Tobin P. Management of
  chemotherapy-induced nausea, vomiting, oral
  mucositis, and diarrhoea. The Lancet
  Oncology,Feb-2005 6(2). Herrstedt J, et al.
  ESMO Minimum Clinical Recommendations for
  prophylaxis of chemotherapy-induced nausea and
  vomiting (NV).Annals of Oncology, 16 (Supplement
  1) i77i79, 2005
• Warr DG, et al. Efficacy and Tolerability of
  Aprepitant for the Prevention of
  Chemotherapy-Induced Nausea and Vomiting in
  Patients With Breast Cancer After Moderately
  Emetogenic Chemotherapy. Journal of Clinical
  Oncology, Vol 23, No 12 (April 20), 2005 pp.
  2822-2830.