Chemotherapy-related nausea and vomiting can be prevented! Causes and treatment

Nausea is an unpleasant sensation felt in the upper stomach and may result in ‘’vomiting’’, the involuntary expulsion of stomach contents. The group of medicines relieving these symptoms is called antiemetics . This article covers the following topics:

1. Types of chemotherapy-related nausea according to onset time
2. Causes of chemotherapy-related nausea and vomiting
3. How is chemotherapy-related nausea and vomiting treated?
4. Chemotherapy drugs according to nausea risk
5. Medicines used as pills according to their potential to cause nausea

Nausea and vomiting are the most feared and worrying side effects for patients and relatives, despite being among the most manageable effects of cancer treatment. Effective treatments can prevent these unpleasant effects that impair the patient's quality of life . We can thus help improve the patient's general health and ease their passage through chemotherapy.

We divide chemotherapy-related nausea into three groups according to onset time

Acute nausea: often starts within the first 1-2 hours of chemotherapy administration and is most intense at 4-6. hours. Delayed nausea: occurs 24 hours after chemotherapy. Particularly with regimens containing high-dose cisplatin, it begins 24 hours after treatment and peaks on days 2. and 3. Timely use of anti-nausea medicines can prevent it. Anticipatory, anxiety-related nausea: nausea beginning before chemotherapy because of distress, particularly after intense nausea during previous chemotherapy.

Looking at the cause of nausea in patients receiving chemotherapy

Nausea results from multifaceted interactions involving the nerve network between the brain's vomiting center and our organs, and the organs' receptors . Medicines developed for treatment act by suppressing these centers and receptors. Nausea and vomiting in chemotherapy patients are divided into patient-related and treatment-related groups, two categories in total.

Patient-related risk factors

• Young (< 50)
• Those with no previous tobacco / alcohol use
• Those susceptible to illnesses
• In daily life, anxiety is intensely experienced by some people
• Those with low overall performance
• Those previously receiving chemotherapy who developed nausea during the earlier treatment

Treatment-related risk factors

• Treatments containing chemotherapy drugs with a high nausea-inducing effect
• The dose and form of the chemotherapy drug used
• Protocols containing multiple chemotherapy drugs

How is chemotherapy-related nausea and vomiting treated?

Agents with different mechanisms of action are available to prevent and treat chemotherapy-related nausea and vomiting. These medicines can prevent nausea either alone or in combination.

5HT3 receptor antagonists

5HT3 (hydroxytryptamine, also called serotonin), these receptors are found in the central and peripheral nervous systems. Their activation activates the brain's nausea and vomiting center. Following discovery of this receptor in the 1950s, drug development dates to 1984, while clinical use in cancer treatment began in 1991.

NK1 receptor antagonists

In 1931, British pharmacology professor John Gaddum discovered in horse brain and intestine a substance called Substance P . It caused blood vessels to contract and relax. In the 1970s, it was shown to be a very widespread protein in both central and peripheral (outside the brain and spinal cord) nervous systems. It acts through three receptors. One, NK1 (Neurokinin 1), mediates stress and pain signals and muscle contraction. Drugs targeting it are used for migraine and prevention of chemotherapy-related nausea.

Multiple receptor antagonists: olanzapine

Initially developed and used for years to treat psychiatric diseases, this drug has also shown anti-nausea and anti-vomiting effects in recent studies. After a study presented at the American Cancer Congress demonstrating olanzapine's (zyprexa) effectiveness was published in the respected NEJM (New England Journal of Medicine), its use for 2-4 days to prevent nausea was approved when highly nausea-inducing chemotherapy drugs are used.

Medicines preventing nausea and vomiting

• 5HT3 receptor antagonists: Ondansetron (onzyd, zofer, zofran), granisetron (emetril, granexa, granitron, kytril, setron), dolasetron (anzemet), palonosetron (aloxi, palodin, palonex)
• Corticosteroids: dexamethasone (dekort, kordexa)
• NK-1 receptor antagonists: aprepitant (emend), fosaprepitant (emend), netupitant (akynzeo), rolapitant (varubi)
• Multiple receptor antagonist: olanzapine (zyprexa)

Other nausea-vomiting treatments

Although rarely needed because current medicines are effective, metoclopramide (metpamid), with a low anti-nausea effect, and centrally acting haloperidol, scopolamine and cannabinoids have also shown effectiveness. However, caution is needed because these medicines suppress the central nervous system and can interact with olanzapine (zyprexa). Combined antiemetic use according to chemotherapy risk classification Your physician will plan these treatments according to your chemotherapy regimen and personal characteristics.

Chemotherapy drugs according to nausea risk

High risk (> %90)

• Anthracycline and cyclophosphamide combination
• Dacarbazine
• Doxorubicin (dose ≥ 60mg/m2)
• Epirubicin (dose > 90mg/m2)
• Ifosfamide (dose ≥ 2g/m2)
• Carmustine (> 250 mg/m2)
• Carboplatin (dose ≥ 4AUC)
• Mechlorethamine
• Cisplatin
• Cyclophosphamide (dose > 1,5g/m2)
• Streptozocin

Moderate risk (%30-90)

• Aldesleukin 12-15 Miu/m2
• Amifostine >300 mg/m2
• Arsenic trioxide
• Azacitidine
• Bendamustine
• Busulfan
• Dactinomycin
• Daunorubicin
• Doxorubicin (dose < 60mg/m2)
• Epirubicin (dose < 90mg/m2)
• Idarubicin
• Ifosfamide (dose < 2g/m2)
• Interferon alfa (10 Miu/m2)
• Irinotecan
• Carboplatin (dose < 4AUC)
• Carmustine 250 mg/m2
• Clofarabine
• Melphalan
• Methotrexate 250 mg/m2
• Oxaliplatin
• Cyclophosphamide
• Cytarabine
• Temozolomide
• Trabectedin

Medicines taken as PILLS according to their nausea-inducing potential

High risk (> %30)

• Altretamine (Hexalen)
• Busulfan (≥ 4 mg/gün) Busulfex, Myleran
• Ceritinib (Zykadia)
• Crizotinib (Xalkori)
• Cyclophosphamide (≥100 mg/m2 /d) (Endoksan)
• Estramustine (Emcyt)
• Etoposide (Lastet)
• Lenvatinib (Lenvima)
• Lomustine (Gleostine)
• Mitotane (Lysodren)
• Olaparib (Lynparza)
• Panobinostat (Farydak)
• Procarbazine (Matulan)
• Rucaparib (Rubcara)
• Temozolomide (>75 mg/m2/gün) (Temodal, Temomid)
• Trifluridine/tipiracil (Lonsurf)

Moderate risk (< %30)

• Afatinib (Gitrif, gilotrif)
• Alectinib (Alecensa)
• Axitinib (Inlyta)
• Bexarotene
• Bosutinib
• Busulfan (< 4 mg/d)
• Cabozantinib (Cometriq)
• Capecitabine (Capeda, Xeltabin, Xeloda)
• Chlorambucil
• Cobimetinib (Cotellic)
• Cyclophosphamide (< 100mg/m2/gün) (Endoksan)
• Dasatinib (Syprcel)
• Dabrafenib (Tafinlar)
• Erlotinib (Tarceva)
• Everolimus (Afinitor)
• Fludarabine (Fludara)
• Gefitinib (Iressa)
• Hydroxyurea (Hydrea)
• Ibrutinib (Imbruvica)
• Idelalisib(Zydelig)
• Imatinib (Glivec)
• Ixazomib (Ninlaro)
• Lapatinib (Tykerb)
• Lenalidomide(Revlimid)
• Melphalan (Alkeran)
• Mercaptopurine (Purinethol)
• Methotrexate
• Nilotinib (Tasigna)
• Osimertinib (Tagrisso)
• Palbociclib (Ibrance)
• Pazopanib (Votrient)
• Pomalidomide(Pomalyst)
• Ponatinib(Iclusig)
• Regorafenib (Stivarga)
• Ruxolitinib(Jakavi)
• Sonidegib(Odomzo)
• Sorafenib (Nexavar)
• Sunitinib (Sutent)
• Temozolomide (Temodal, Temomid)
• Thalidomide(Thalomid)
• Thioguanine (Tabloid)
• Topotecan (Hycamptin)
• Trametinib (Mekinist)
• Tretinoin (Vesanoid)
• Vandetanib (Caprelsa)
• Vemurafenib (Zelboraf)
• Venetoclax (Venclexta)
• Vismodegib (Erivedge)
• Vorinostat (Zolinza)