Appendix 5 - Antiemetics

Guidelines For Use Of 5-HT₃ Antagonists In Non-Hematologic, Non-Gynecologic Malignancies

5-HT₃ antagonists are indicated as first-line therapy in the use of moderate-severely emetogenic chemotherapy. Use is recommended up to two days only after chemotherapy is finished except in exceptional cases it can be used beyond two days. There are three 5-HT3 antagonists currently approved for use: dolasetron (anzemet®), granisetron (kytril ®), and ondansetron (zofran ®).

Classification of Emetogenicity - Single Agents

1. Level I (<10% incidence of emesis)
   1. vinca alkaloids
   2. bleomycin
   3. methotrexate ( 50 mg/m2)
   4. hydroxyurea
      
2. Level II (10 - 30% incidence of emesis)
   1. methotrexate (> 50 mg/m2 and < 250 mg/m2)
   2. mitomycin C
   3. 5-fluorouracil
   4. etoposide
   5. gemcitabine
   6. taxanes (docetaxel, paclitaxel)
      
3. Level III (30 - 60% incidence of emesis)
   1. methotrexate 250 - 1000 mg/m2)
   2. cyclophosphamide ( 750 mg/m2)
   3. oral cyclophosphamide (single agent)
   4. doxorubicin (< 40 mg/m2 or 25 mg/m2 in combination)
   5. epirubicin (< 40 mg/m2 single agent or < 25 mg/m2 in combination)
   6. mitoxantrone
   7. ifosfamide
      
4. Level IV (60 - 90% incidence of emesis)
   1. oral procarbazine
   2. methotrexate (> 1000 mg/m2 )
   3. doxorubicin ( 40 mg/m2 single agent or > 25 mg/m2 in combination)
   4. epirubicin ( 40 mg/m2 single agent or 25 mg/m2 in combination)
   5. dactinomycin
   6. cyclophosphamide > 750 mg/m2
   7. cisplatin 50 mg/m2
   8. carboplatin
   9. carmustine 250 mg/m2
   10. CPT-11 (irinotican)
       
5. Level V (< 90% incidence of emesis)
   1. cisplatin 50 mg/m2
   2. carmustine > 250 mg/m2
   3. dacarbazine
   4. streptozocin

Classification of Commonly Used Combination Regimens.

1. Mildly-emetogenic
   1. 5-fluorouracil/folinic acid
   2. CMF (oral or iv regimens); cyclophosphamide, methotrexate, 5-fluorouracil
      
2. Moderately emetogenic
   1. FEC (5-fluorouracil, epirubicin, cyclophosphamide)
   2. FAC (5-fluorouracil, adriamycin, cyclophosphamide)
   3. CAV (cyclophosphamide, adriamycin, vincristine)
   4. ELF (etoposide, leucovorin, 5-fluorouracil)
      
3. Severely emetogenic
   1. BEP (bleomycin, etoposide, cisplatin)
   2. EC (etoposide, cisplatin)
   3. PVC (procarbazine, vincristine, carmustine)
   4. BCD (BCNU, cisplatin, dacarbazine)
   5. cisplatin/navelbine
   6. cisplatin/etoposide

Indications for Use of 5-HT3 Antagonists as First-Line Therapy for the Management of Acute Nausea and Vomiting.

1. Level IV single agents
2. Level V single agents
3. Severely emetogenic combination chemotherapy regimens

For Level III single agents and moderately emetogenic combination chemotherapy regimens, the use of 5-HT3 antagonists may be required. Other factors which may have to be factored in to the decision are sex (female), age (young), and performance status (poor) which increases the risk of emesis.

For Level I - II single agents and mildly emetogenic combination chemotherapy regimes, the use of 5-HT3 is not indicated as first-line antiemetic therapy.

For Level I - III single agents. Mild to moderately emetogenic combination chemotherapy regimens, the use of 5-HT3 antagonists is required in patients who experience significant nausea and vomiting despite use of standard antiemetics (ie. metoclopramide, dexamethasone, or stemetil)

Types of 5-HT3 Antagonists.

There are three 5-HT3 antagonists approved for use in Canada.

1. Dolasetron (Anzemet ®) 100 mg, p.o. on day of chemotherapy.
2. Granisetron (Kytril ®) 2 mg p.o. on day of chemotherapy or 1 mg p.o., b.i.d. on day of chemotherapy
3. Ondansetron (Zofran ®)
   8 mg p.o., b.i.d. for duration of chemotherapy and 24 hours after for moderately emetogenic regimens
   8 mg p.o., t.i.d. for duration of chemotherapy and 24 hours after for severely emetogenic regimens.

For multi-day regimens that require 5-HT3 antagonists, the medications would be given each day as per instructions.

Delayed Onset Emesis

The use of 5-HT3 antagonists in the prevention of delayed onset emesis is no more effective than with standard medications. Therefore, the use of 5-HT3 antagonist is not indicated as first-line treatment of delayed emesis. They may be indicated in patients who failed standard therapy for delayed emesis.