*For medical professionals only
Written by | Gao Lili
Chemotherapy is the abbreviation of chemotherapy treatment, which is a treatment method that uses chemical drugs to prevent the proliferation, invasion, metastasis of cancer cells, and finally kill cancer cells. While killing or inhibiting tumor cells, it will also affect the normal cells of the body (especially those with vigorous metabolism), and then cause a series of adverse reactions, such as cardiotoxicity of anthracyclines and bladder toxicity of cyclophosphamide (CTX)/ifosfamide (IFO). Therefore, pretreatment before chemotherapy can alleviate some adverse reactions related to chemotherapy drugs, so as to ensure the successful completion of chemotherapy.
1. Drugs to prevent nausea and vomiting
Antineoplastic drugs often cause nausea and vomiting, with chemotherapy-induced nausea and vomiting (CINV) being the most severe. CINV refers to nausea [a state characterized by nausea and/or urgent vomiting] and vomiting caused by or associated with chemotherapy drugs, which can be classified into acute CINV, delayed CINV, anticipatory CINV, fulminant CINV, and refractory CINV according to the timing of occurrence and treatment effect. At present, anti-nausea and vomiting drugs mainly include 5-HT3 receptor antagonists, NK-1 receptor antagonists, glucocorticoids, atypical antipsychotic drugs, benzodiazepines, phenothiazines and other drugs.
01
Prevention of nausea and vomiting caused by intravenous drugs at high risk of emetemia
Chemotherapy drugs: AC regimen (combination regimen containing anthracyclines and cyclophosphamide); Carboplatin AUC≥4; carmustine > 250 mg/m2; Cisplatin; cyclophosphamide≥1.5g/m2; Dacarbazine; doxorubicin≥ 60mg/m2; epirubicin> 90mg/m2; ifosfamide ≥ 2 g/m2 (per dose); nitrogen mustard; Streptozocin.
Choice of prophylactic drugs:
(1) It is recommended to use a three-drug combination regimen before chemotherapy, with 5-HT3 receptor antagonist + dexamethasone + NK-1 receptor antagonist preferred, and if fulminant or refractory vomiting still occurs, the addition of olanzapine can be considered, which can significantly alleviate anxiety and depression.
(2) Thalidomide + palonosetron + dexamethasone can prevent delayed nausea and vomiting in treatment-naïve chemotherapy patients, and has advantages in alleviating anorexia.
(3) According to the Shanghai Expert Consensus on the Management of Nausea and Vomiting Caused by Chemotherapy (2018 Edition):
- 急性期5-HT3受体拮抗剂+地塞米松+NK-1受体拮抗剂±劳拉西泮±抑酸剂（PPI或H2受体拮抗剂）；备选1：5-HT3受体拮抗剂+地塞米松+NK-1受体拮抗剂+奥氮平；备选2：5-HT3受体拮抗剂+地塞米松+奥氮平。
- delayed dexamethasone + NK-1 receptor antagonist ±lorazepam± antacids; Option 1: dexamethasone + NK-1 receptor antagonist + olanzapine (or mirtazapine); Option 2: dexamethasone + thalidomide.
02
Prevention of nausea and vomiting caused by intravenous drugs at moderate risk of emetemia
化疗药物：苯达莫司汀；白消安；卡铂AUC<4；卡莫司汀≤250mg/m2；环磷酰胺≤1.5g/m2；阿糖胞苷＞200mg/m2；放线菌素D；柔红霉素；多柔比星＜60mg/m2；表柔比星≤90mg/m2；异环磷酰胺＜2g/m2（每剂）；伊立替康；洛铂；美法仑；甲氨蝶呤≥250mg/m2；奈达铂；奥沙利铂；替莫唑胺等。
Choice of prophylactic drugs:
(1) The standard dual regimen of 5-HT3 receptor antagonist combined with dexamethasone is recommended, and patients with anxiety or depression tendencies can consider adding olanzapine.
(2) For patients with other risk factors or who have failed previous treatment with "corticosteroid + 5-HT3 receptor antagonist", a combination regimen of dexamethasone + 5-HT3 receptor antagonist + NK-1 receptor antagonist should be used.
(3) According to the Shanghai Expert Consensus on the Management of Nausea and Vomiting Caused by Chemotherapy (2018 Edition), 5-HT3 receptor antagonists + dexamethasone ±NK-1 receptor antagonists ±lorazepam± antacids (PPI or H2 receptor antagonists) in the acute phase; Delayed phase 5-HT3 receptor antagonist + dexamethasone ± NK-1 receptor antagonist ±lorazepam or NK-1 receptor antagonist ± dexamethasone ±lorazepam.
03
Prevention of nausea and vomiting caused by intravenous drugs with low risk of emetemia
Chemotherapy drugs: carfilzomib; cytarabine 100-200mg/m2; docetaxel; doxorubicin liposomes; Etoposide; 5-fluorouracil; gemcitabine; irinotecan (liposome); methotrexate 50-250mg/m2; mitomycin; mitoxantrone; homoharringtonine; paclitaxel; paclitaxel (albumin-bound); pemetrexed; raltitrexed; Settipa; Topotecan, etc.
Choice of prophylactic drugs:
(1) It is recommended to use a single antiemetic drug, and 5-HT3 receptor antagonists, dexamethasone, dopamine receptor antagonists (such as metoclopramide) or chlorpromazine are recommended to prevent vomiting.
(2) According to the Shanghai Expert Consensus on the Management of Nausea and Vomiting Caused by Chemotherapy (2018 Edition), dexamethasone in the acute phase; metoclopramide; Prochlorperazine; Promethazine; 5-HT3 receptor antagonists (both ± lorazepam ±antacids), antacids are especially suitable for people with gastric diseases.
04
Prevention of nausea and vomiting caused by intravenous drugs at risk of mild emetemia
Chemotherapy drugs: bleomycin; bortezomib; Cytarabine < 100mg/m2; decitabine; fludarabine; Methotrexate ≤ 50mg/m2; Vincreatine drugs (vincristine, vincristine liposome, vinorelbine, vinblastine), etc.
Selection of prophylactic drugs: patients without a history of nausea and vomiting do not need to routinely use antiemetic drugs before chemotherapy. If vomiting occurs, it can be managed according to the prevention of nausea and vomiting caused by intravenous drugs with a low risk of emetemia.
05
Prevention of nausea and vomiting caused by intravenous chemotherapy for multiple days
Choice of prophylactic drugs:
(1) Patients receiving multi-day chemotherapy drugs have a dual risk of acute and delayed nausea and vomiting, and the emetic potential varies depending on the chemotherapy drugs used and the order of use.
(2) The standard treatment recommends 5-HT3 receptor antagonists combined with dexamethasone, and it is usually advocated that 5-HT3 receptor antagonists should be used throughout chemotherapy, and dexamethasone should be used continuously until 2-3 days after the end of chemotherapy.
(3) For multi-day chemotherapy regimens with high risk of high emetogenic or delayed nausea and vomiting (such as cisplatin-containing multi-day regimens), NK-1 receptor antagonists can be considered, and the use of NK-1 receptor antagonists can be extended to the 7th day of chemotherapy at most.
(4) Compound netupitant/palonosetron capsule can be considered in the multi-day chemotherapy hyperemetic regimen. Granisetron transdermal patch can reduce the fluctuation of blood concentration, can smoothly control nausea and vomiting for 7 days, and can be used as one of the 5-HT3 receptor antagonists for nausea and vomiting caused by multi-day chemotherapy.
06
Prevention of nausea and vomiting caused by oral medications with moderate to high risk of vomiting
化疗药物：白消安≥4mg/d；环磷酰胺≥100mg/（m2·d）；依托泊苷；米托坦；丙卡巴肼；替莫唑胺＞75mg/m2等
Choice of prophylactic drugs:
(1) 5-HT3 receptor antagonists can be administered daily, and oral or topical dosage forms are recommended.
(2) According to the Shanghai Expert Consensus on the Management of Nausea and Vomiting Caused by Chemotherapy (2018 Edition), 5-HT3 receptor antagonists in the acute phase ±lorazepam± antacids (PPI or H2 receptor antagonists), which are especially suitable for patients with gastric diseases.
07
Prevention of nausea and vomiting caused by low-mild risk of vomiting with oral medications
Chemotherapy drugs: busulfan <4mg/d; Capecitabine; chlorambucil; cyclophosphamide <100mg/(m2·d); everolimus; fludarabine; hydroxyurea; Ishazomib; Melphalan; mercaptopurine; Methotrexate; Tigio; Temozolomide ≤75mg/(m2·d); thioguanine; Topotecan, etc.
Choice of prophylaxis: not routinely prophylaxis, only with 5-HT3 receptor antagonists, metoclopramide, or chlorpromazine alone when necessary.
2. Drugs to prevent allergic reactions
Almost all chemotherapy drugs can cause allergic reactions to a greater or lesser extent, such as taxanes, asparaginase, platinum drugs, teniposide, anthracyclines, cytarabine, cyclophosphamide, ifosfamide, pemetrexed, etc. At present, anti-allergic drugs mainly include antihistamines, glucocorticoids, calcium, etc.
Taxane drugs can be divided into paclitaxel (solvent-based paclitaxel, paclitaxel liposome and paclitaxel albumin-bound type) and polyene paclitaxel (docetaxel), the incidence of allergic reactions is 30-41%, and the incidence of severe allergic reactions is 2-5%, mainly manifested as skin itching, flushing, dyspnea, nausea, diffuse urticaria, angioedema, etc., and can cause death in severe cases. Prior to taxane infusion (except for nab-paclitaxel), glucocorticoids combined with histamine H1 and H2 receptor antagonists can be used to prevent hypersensitivity reactions.
Some glucocorticoid pretreatment regimens will cause hormone-related adverse reactions, such as iatrogenic Cushing syndrome, adrenal insufficiency, concurrent infection, etc., and glucocorticoid simplified pretreatment regimens can be selected, including dexamethasone dose reduction pretreatment regimen and dexamethasone discontinuation pretreatment regimen.
3. Drugs to prevent cardiotoxicity
A variety of chemotherapy drugs can cause cardiotoxicity, such as anthracyclines, taxanes and fluorouracil, among which anthracyclines are the most common drugs that cause cardiotoxicity.
Anthracycline-induced cardiotoxicity is usually progressive and irreversible, and may cause cardiac damage with initial use, and can be divided into acute, chronic, and delayed cardiotoxicity, with chronic and delayed cardiotoxicity positively correlated with the cumulative dose of the drug. Dextropropylimide (DZR, dextrorazoxen) is the only drug that is effective in preventing anthracycline-induced cardiotoxicity and reducing the incidence of heart failure.
4. Drugs to prevent hemorrhagic cystitis
The alkylating agents cyclophosphamide (CTX) and ifosfamide (IFO) can be used for the treatment of a variety of malignant tumors, but IFO and high-dose CTX can cause hemorrhagic cystitis, with an incidence of 5-40%, mainly manifested as hematuria, urinary frequency, urgency, dysuria, etc. CTX and IFO can produce acrolein metabolites, which are discharged to the bladder through the kidneys and are the main substances causing urinary tract toxicity.
Mesna is a specific urinary tract protector that can be rapidly transformed into its metabolite dimesna in the body by the catalytic oxidation of enzymes. Mesna and dimesna are extremely hydrophilic and can be retained in blood vessels and quickly cleared by the kidneys. Mesna sulfhydryl (SH) can react with nephrotoxic acrolein and 4-hydroxy metabolites produced by CTX and IFO metabolism in the urine to form stable non-toxic components, and quickly excrete them from the body, thereby preventing acrolein-caused hemorrhagic cystitis and other urinary system damage, and significantly reducing the incidence of hemorrhagic cystitis.
Dosage: The Chinese National Formulary· Chemical Drugs and Biological Products Volume ·Children's Edition" recommends intravenous injection, the commonly used dose is 20% of IFO and CTX, and the time is 0, 4 hours and 8 hours.
In addition, adequate hydration, alkalinization of urine, and diuresis to maintain adequate urine output are the most basic and critical measures to prevent nephrotoxicity.
5. Miscellaneous
Amfostine (amifutin) is a normal cell protective agent of organic phosphorus sulfide compounds, which can scavenge free radicals produced by chemotherapy drugs in tissues and promote the rapid repair of cellular DNA, and directly bind to the activated metabolites of alkylating agents and platinum-based chemotherapy drugs, and play a role in reducing the toxicity of chemotherapy drugs. It is clinically used in the adjuvant treatment of cancer, and the use before chemotherapy can significantly reduce the toxicity of the kidney, bone marrow, heart, ear and nervous system produced by chemotherapy drugs, without affecting the efficacy of chemotherapy drugs.
According to the "Expert Recommendations Series on Clinical Practical Hot Issues in Childhood Immune-related Diseases - Recommendations on the Application of Methotrexate in Childhood Rheumatic Diseases in China" (2020), it is recommended that weekly folic acid supplementation during MTX treatment can reduce the incidence of skin and mucosal damage, abnormal blood images, gastrointestinal adverse reactions and elevated aminotransferases, and the dose of folic acid is 1/3 of the MTX dose, because this dose can effectively prevent the adverse reactions of MTX. The plasma half-life of MTX is 4.5-10 hours, and the renal excretion rate is 90% within 24 hours, so folic acid should be taken after 24 hours of MTX application to avoid reducing the efficacy of MTX, and once a week.
Thymus nucleoside reductase inhibits 5-fluorouracil (5-FU) and can be given calcium folinate (CF) first, followed by 5-FU to increase the efficacy. Dihydrofolate reductase inhibitor pemetrexed should be supplemented with folic acid and vitamin B12 at the same time, which can reduce treatment-related blood toxicity and gastrointestinal toxicity, take folic acid 400μg at least 5 times in the first 7 days of use, and take the entire treatment cycle, intramuscular injection of vitamin B12 1000 μg/time within the first 7 days of use, and intramuscular injection every 3 cycles thereafter.
Recombinant human granulocyte colony-stimulating factor, pegylated recombinant human granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor may be considered for the prevention of chemotherapy-induced neutropenia in patients with indication; Use of platelet growth factor (recombinant human interleukin-11, recombinant human thrombopoietin) to prevent chemotherapy-induced thrombocytopenia.
Vitamin B6 is commonly used to prevent hand-foot syndrome (HFS).
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