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Pediatric Chemotherapy-Induced Nausea and Vomiting Treatment & Management

  • Author: Reuven J Schore, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
 
Updated: Sep 16, 2015
 

Medical Care

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 a single agent or as combination therapy (see the Table and specific recommendations below). 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

For most children, receiving any chemotherapy that has emetogenic potential (ie, any agents except those in level 1), a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist should form the backbone of antiemetic therapy. No studies have demonstrated superiority of any 5-HT3 antagonist over another when used optimally (see Medication for dosing guidelines). For maximum efficacy, these agents should be started 30 minutes prior to chemotherapy, continued throughout chemotherapy, and continued for several days after completion.

Children who are receiving highly emetogenic chemotherapy may benefit from additional antiemetics. If no contraindications to dexamethasone are noted, adding this agent to a 5-HT3 agonist may be beneficial, particularly in those patients receiving cisplatin-containing chemotherapy regimens. This can help with both acute and delayed nausea. Relative contraindications to dexamethasone include hyperglycemia, systemic infection, and hypertension. Dexamethasone should generally be avoided in patients receiving chemotherapy regimens that include corticosteroids and was recently found to increase the risk of postoperative bleeding in patients after tonsillectomy.[3]

Aprepitant is a neurokinin receptor (NK)-1 antagonist that is indicated in combination with other antiemetic agents for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic and highly emetogenic cancer chemotherapy (including high-dose cisplatin).[4]  In September 2015, its indication for CINV was expanded to include children aged ≥12 years or children <12 years who weigh at least 30 kg. In December 2015, the indication was expanded to include children aged 6 months or older.

Approval of aprepitant in children was based on findings from a randomized, double-blind, active-comparator-controlled trial in children aged 6 months to 17 years that compared aprepitant plus ondansetron with ondansetron alone (control group). Each group was allowed to receive IV dexamethasone at the discretion of the physician. The primary endpoint was complete response (no vomiting, retching and no use of rescue medication) in the acute phase (0 to 24 hours) and in the delayed phase (25 to 120 hours following initiation of chemotherapy). Seventy-seven (51%) of 152 patients in the aprepitant group and 39 (26%) of 150 in the control group achieved a complete response in the delayed phase (p<0.0001). For patients aged 12-17 years and patients <12 years who weighed at least 30 kg (n=132), a higher complete response was observed in the acute and delayed phases with the aprepitant regimen (55.6% and 49.2%) compared with the control regimen (37.7% and 18.8%).[5]

 

Table. Emetogenic Risk of Intravenously Administered Antineoplastic Agents[2, 6] (Open Table in a new window)

Emetogenic Risk level Antineoplastic Agents Antiemetic Regimen
level 4 (High): More than 90% of patients who receive these agents experience nausea and vomiting. Carmustine, cisplatin, cyclophosphamide (>1500 mg/m2), dacarbazine, dactinomycin, mechlorethamine, streptozotocin Serotonin-receptor antagonist,



dexamethasone, and aprepitant



level 3 (Moderate): Nausea and vomiting occurs in 30-90% of patients who receive these agents. Carboplatin, cyclophosphamide (< 1500 mg/m2), cytarabine (>1 g/m2), daunorubicin, doxorubicin, epirubicin, idarubicin, ifosfamide, irinotecan, oxaliplatin Serotonin-receptor antagonist and dexamethasone
level 2 (Low): Nausea and vomiting occurs in 10-30% of patients who receive these agents. Bortezomib, cetuximab, cytarabine (< 1 g/m2), docetaxel, etoposide, fluorouracil, gemcitabine, methotrexate, mitomycin, mitoxantrone, paclitaxel, pemetrexed, topotecan, trastuzumab Serotonin-receptor antagonist
level 1 (Minimal): Less than 10% of patients who receive these agents experience nausea and vomiting. Bevacizumab, bleomycin, busulfan, 2-chlorodeoxyadenosine, fludarabine, rituximab, vinblastine, vincristine, vinorelbine No antiemetic routinely administered*
*If antiemetic required for individual patients, may use a single dose of serotonin-receptor antagonist

 

In addition to the scheduled antiemetics determined by the emetogenic potential of the planned regimens, medications must also be available as needed for breakthrough nausea, vomiting, or both. Commonly used antiemetics or adjuncts include the combination of diphenhydramine and promethazine (not recommended in children < 2 y), lorazepam, metoclopramide, and dronabinol. See below and Medication for dosing guidelines.

Lorazepam is particularly useful when anticipatory nausea is a contributing factor. Dronabinol is most useful when started prior to chemotherapy (ie, started in anticipation of a second cycle of chemotherapy in a patient who experienced significant nausea or emesis during the first cycle). Diphenhydramine, promethazine, and lorazepam may cause drowsiness, and, in some cases, a balance must be reached by the patient in terms of emesis relief and sleepiness.

  • 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.[7, 8]
  • Anticipatory nausea and vomiting: Hypnosis is a behavioral intervention technique that reduces anticipatory and post chemotherapy nausea and vomiting. [9, 10]

Specific recommendations are as follows:

  • 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").
    • 5-HT3 serotonin-receptor antagonist (eg, ondansetron [0.15 mg/kg/dose IV for 3 doses; not to exceed 16 mg/dose]) with or without promethazine (0.25-1 mg/kg/dose IV q4-6h prn [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:
      • Metoclopramide (plus diphenhydramine to decrease risk of extrapyramidal adverse effects): 1 mg/kg/dose intravenously or orally every 6 h as needed
      • Lorazepam: 0.02-0.05 mg/kg/dose intravenously or orally every 6 h as needed
      • Diphenhydramine: 1 mg/kg/dose intravenously or orally every 6 h as needed
      • Dronabinol: 5 mg/m2/dose orally every 4-6 h as needed
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Consultations

See the list below:

  • 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.
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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
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Contributor Information and Disclosures
Author

Reuven J Schore, MD Assistant Professor of Pediatrics, George Washington University School of Medicine and Health Sciences; Attending Physician, Center for Cancer and Blood Disorders, Leukemia and Lymphoma Program, Division of Oncology, Children's National Medical Center

Reuven J Schore, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Received research grant from: Millennium Pharmaceuticals, Inc; Onyx Pharmaceuticals, Inc; Merck Inc<br/>Received income in an amount equal to or greater than $250 from: Baxalta Pharmaceuticals, Inc.

Coauthor(s)

Devona Williams, PharmD Pharmacy Clinical Specialist, Children's National Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

References
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Vomiting reflex.
Table. Emetogenic Risk of Intravenously Administered Antineoplastic Agents [2, 6]
Emetogenic Risk level Antineoplastic Agents Antiemetic Regimen
level 4 (High): More than 90% of patients who receive these agents experience nausea and vomiting. Carmustine, cisplatin, cyclophosphamide (>1500 mg/m2), dacarbazine, dactinomycin, mechlorethamine, streptozotocin Serotonin-receptor antagonist,



dexamethasone, and aprepitant



level 3 (Moderate): Nausea and vomiting occurs in 30-90% of patients who receive these agents. Carboplatin, cyclophosphamide (< 1500 mg/m2), cytarabine (>1 g/m2), daunorubicin, doxorubicin, epirubicin, idarubicin, ifosfamide, irinotecan, oxaliplatin Serotonin-receptor antagonist and dexamethasone
level 2 (Low): Nausea and vomiting occurs in 10-30% of patients who receive these agents. Bortezomib, cetuximab, cytarabine (< 1 g/m2), docetaxel, etoposide, fluorouracil, gemcitabine, methotrexate, mitomycin, mitoxantrone, paclitaxel, pemetrexed, topotecan, trastuzumab Serotonin-receptor antagonist
level 1 (Minimal): Less than 10% of patients who receive these agents experience nausea and vomiting. Bevacizumab, bleomycin, busulfan, 2-chlorodeoxyadenosine, fludarabine, rituximab, vinblastine, vincristine, vinorelbine No antiemetic routinely administered*
*If antiemetic required for individual patients, may use a single dose of serotonin-receptor antagonist
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