Professor Elhamy Rifky 2010

1. Professor Elhamy Rifky 2010 Chemotherapy-Induced Nausea and Vomiting

2. The outcome for children with cancer has dramatically improved over the past several decades, in part because of the ability to effectively and safely deliver higher and more intense courses of chemotherapy.

3. Two of the most common side effects of this treatment modality are : Nausea and vomiting. These side effects have a significant impact on quality of life and can interfere with the ability to deliver intensive care. Fortunately, improvements in supportive care have also been attained, and current treatments for nausea and vomiting are effective in mitigating these adverse effects in most patients.

4. DEFINITIONS Vomiting refers to the expulsion of stomach contents.  Retching refers to the act of vomiting without expulsion of stomach contents. Nausea is the child’s perception of needing to vomit. Acute vomiting refers to symptoms that occur within 24 hours of the administration of chemotherapy. Delayed vomiting refers to vomiting 2-5 days after the CMT. Anticipatory vomiting: is vomiting prior to the administration of chemotherapy. Anticipatory vomiting is a learned response that is best prevented by the use of an adequate antiemetic regimen during the patient’s first experience with chemotherapy.

6. FREQUENCY The frequency of nausea and vomiting is related to the emetogenic risk of the particular chemotherapeutic agent or combination of drugs being administered . Cisplatin is one of the most emetogenic agents and is known to produce nausea in more than 99% of patients if no antiemetic are used. In order to determine the emetogenic potential of combination chemotherapy regimens, the following must be considered: • Determine the category of the most emetogenic agent in the regimen. • Add one level for all level 2 agents or each level 3 agent included in the regimen.  • Level 1 agents do not contribute to the emetogenicity of a given regimen.

7. Emetogenic Potential

8. Morbidity Nausea and vomiting are a significant cause of morbidity in pediatric patients. Sex Although both sexes are affected by chemotherapy-induced nausea and vomiting, some studies have suggested that females are somewhat more susceptible. Age Chemotherapy-induced nausea and vomiting affects children of all ages; however, children younger than 6 years have been shown to have a lower incidence than older children when receiving similar agents. By contrast, adolescents appear to be more susceptible.

9. CLINICAL History The history is useful in eliciting information to help establish an effective antiemetic regimen and in ruling out other potential causes beyond chemotherapy-induced nausea and vomiting. Physical The physical examination should assess for other potential causes of nausea and vomiting, including a funduscopic examination to look for signs of increased intracranial pressure, any signs of GI system obstruction or ileus, and signs of dehydration.

10. DIFFERENTIAL DIAGNOSES Many other potential causes of nausea and vomiting may contribute to symptoms in children receiving chemotherapy:  • Direct effects of tumor by stretching organs of the GI system or causing obstruction • Postoperative obstruction (in patients who have had abdominal surgery) • Increased intracranial pressure  • Opioid-induced vomiting

11. WORKUP Laboratory Studies In cases of severe or persistent emesis, monitoring serum electrolyte levels may be warranted. Imaging Studies Imaging studies are useful if chemotherapy is not thought to be solely responsible for the nausea and vomiting. Abdominal imaging (radiography or CT scanning) or CNS imaging (head CT scanning) may be indicated depending on the potential cause under investigation

12. THE MANAGEMENT OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING A. Timing: Therapy must be started before chemotherapy and must be continuous and individualized for each patient. B. Administration route: The route of administration should be IV if venous access is available and practical. The oral route requires earlier administration (before the start of chemotherapy) because of slower absorption. Avoid rectal use whenever possible. C. Duration: the duration of antiemetic treatment depends on the schedule of chemotherapy, expected delayed effect, and patient response. D. Drug combinations: Two or more classes of drug may be combined to optimize effectiveness (e.g., ondansetron and Decadron).

13. MANAGEMENT The goal of antiemetic therapy is to prevent nausea and vomiting associated with chemotherapy administration. The appropriate pharmacologic treatment should be chosen by evaluating the emetogenic risk of chemotherapy as single agent or as combination therapy. In the event of uncontrolled nausea or vomiting, several medical complications may arise, including fluid and electrolyte imbalances, poor nutrition status, prolonged hospitalization, and delay in subsequent chemotherapy administration cycles

14. LOW EMETOGENIC POTENTIAL (<10% ) • Vincristine. • Vinblastine • Chlorambucil. • Cytarabine (low dose)

15. LOW EMETOGENIC POTENTIAL START WITH: R/Metaclopramide (Primperan) 10mg/sqm P.O. …. 30 minutes before chemotherapy then q.6 h after chemotherapy Injections: 5 mg/ml Syrup: 5 mg/5 ml (1 tsp/10kg/day) Drops: 2.5 mg/ml (1 drop/kg/dose) NB: Metaclopramide (Primperan) has both central (blocks the CTZ by blocking Dopamine) and peripheral (accelerates gastric emptying) actions. It causes extra pyramidal reactions.

16. IF EMESIS CONTINUES R/ Add: + Dexamethasone (Decadron) Dosage not established. 10 mg IV before and 4 mg IV or PO q4h after Chemotherapy (can be varied/ individualized). Phenadon Syrup : 0.5 mg/5 ml. Decadron Vials: 8 mg/2 ml NB: Action unknown IF EMESIS CONTINUES: Add:R/ Diazepam (Valium) 0.2 mg/kg IV over 3 minutes q6h; maximum 0.6 mg/kg per day in 4 divided doses Injections: 10 mg/2 ml. Liquid: Stesolid Liquid 2 mg/ 5 ml NB: Benzodiazepines have no antiemetic effect but cause antegrade amnesia.

17. MODERATE EMETOGENIC POTENTIAL (50%) • L-Asparagwiase • Cyclophosphamide • Doxorubicin • Daunorubicin • Carboplatin • 6-Mercaptopurine • Methotrexate (low dose) • Bleomycin • 6-Thioguanine • Thiotepa • Etoposide • Tenoposide

18. MODERATE EMETOGENIC POTENTIAL START WITH R/Dexamethasone (Decadron) With chemotherapy 4 mg/sqm by slow IV injection then 2 mg/sqm three times /day for 2 days + R/ Metaclopramide (Primperan) 10mg/sqm P.O. …. Every 6 hours for 2 days to prevent delayed emesis.

19. HIGH EMETOGENIC POTENTIAL (>90%) Cisplatin Cytarabine (high dose) Methotrexate (high dose) Actinomycin-D Nitrosoureas (BCNU, CCNU) 5-fluorouracil Procarbazine Dacarbazine (DTIC) Nitrogen mustard Ifosphamide

20. HIGH EMETOGENIC POTENTIAL START WITH R/Ondansetron (Zofran). 0.15 mg/kg IV 30 minutes before and 4 and 8hrs after chemotherapy. Available as a 2 mg/ml in 20 ml multidose vial. NB: Ondansetron (Zofran) is a serotonin antagonist that does not cause sedation and only rarely causes an extrapyramidal reaction. Headache and diarrhea are possible side effects. + R/Dexamethasone 4mg/sqm PO with chemotherapy then 2mg/sqm PO three times/day for 2 days.

21. FOR PATIENTS WITH ANTICIPATORY OR DELAYED VOMITING R/ Diazepam (Valium) 0.2 mg/kg IV over 3 minutes q6h; maximum 0.6 mg/kg per day in 4 divided doses Injections: 10 mg/2 ml – Liquid: Stesolid Liquid 2 mg/ 5 ml NB: Benzodiazepines have no antiemetic effect but cause antegrade amnesia.

22. ACUTE AND DELAYED NAUSEA AND VOMITING • Monitor serum electrolytes, with special attention to sodium, potassium and bicarbonate status. In patients with uncontrolled vomiting and poor oral intake, replacement with intravenous fluids that contain sodium chloride and potassium chloride may be necessary. • Monitor the number of vomiting episodes and quantify fluid loss. Encourage oral intake of liquids. If unable to tolerate oral intake, replace losses with intravenous fluids to prevent dehydration. • If unable to maintain appropriate caloric intake enterally, consider initiation of parenteral nutrition. • Acupuncture, as an addition to standard antiemetic medication, is associated with a reduction in the need for subsequent rescue antiemetic medications.

23. ANTICIPATORY NAUSEA AND VOMITING Hypnosis is a behavioral intervention technique that reduces anticipatory and post chemotherapy nausea and vomiting.8 9

24. SOME SPECIFIC RECOMMENDATIONS • Anticipatory nausea, emesis, or both: Add lorazepam (0.02-0.05 mg/kg/dose intravenously every 6 h as needed) to the regimen. • Breakthrough and refractory emesis: If nausea and vomiting is controlled, continue breakthrough medication on a scheduled regimen (ie, not "as needed"). • Ondansetron [0.15 mg/kg/dose intravenously; not to exceed 3 doses in 24 h]) with or without promethazine (0.25-1 mg/kg/dose intravenously every 4-6 h as needed [with or without diphenhydramine]) • Prochlorperazine: 0.1 mg/kg/dose intravenously every 8-12 h as needed (with or without diphenhydramine to decrease risk of extrapyramidal adverse effects), and with or without the following:

25. CONSULTATIONS Consult a clinical dietician for recommendations of intravenous fluid replacement or parenteral nutrition formulas to meet age-appropriate caloric and fluid intake goals in patients with fluid and electrolyte problems due to uncontrolled vomiting. Consult a psychologist or other mental health professional experienced in working with patients with cancer if evidence of anticipatory nausea or vomiting are observed.

26. DIET Instruct patients as follows • Eat small, frequent meals or snacks. • Drink plenty of water and noncaffeinated liquids to avoid dehydration. • Avoid greasy or spicy foods. • Eat dry foods such as crackers, toast, or dry cereals. • Eat soft, bland foods that are easy to digest

27. FOLLOW-UP Further Inpatient Care • Monitor serum laboratory values and correct for abnormalities of fluid and electrolyte status due to episodes of chemotherapy-induced vomiting. • Monitor and supplement nutritional needs as appropriate for the child’s age.

28. Further Outpatient Care • Ensure episodes of emesis are well controlled prior to discharge. • Monitor serum laboratory levels in the ambulatory setting and correct for abnormalities of fluid and electrolyte status due to vomiting. • Educate patients and caregivers on mechanisms of rehydration and the importance of oral hydration during chemotherapy and following periods of vomiting. • Verify patients and caregivers are able to maintain proper nutritional status for patients at home. Provide nutrition supplements as needed.

29. INPATIENT & OUTPATIENT MEDICATIONS Antiemetic prophylaxis should always be initiated prior to administration of emetogenic chemotherapy. If infusions are administered in an ambulatory setting, provide patients and caregivers with appropriate prescriptions and instructions prior to initiation of emetogenic chemotherapy.

30. COMPLICATIONS • Patient discomfort • Electrolyte imbalance • Dehydration • Poor nutrition • Prolonged hospitalizations

31. PROGNOSIS • Selection and modification of appropriate antiemetic therapy based on emetogenic potential of chemotherapy scheduled, prior patient experience, and patient risk factors increase the opportunity for administration of chemotherapy without emetic complications.

32. PATIENT EDUCATION • Importance of adequate hydration • Adherence to schedules antiemetic regimen • Maintaining chemotherapy treatments as scheduled • Diet modifications to decrease emesis risk

34. Thank you for your attention