Toxic side effects are almost inevitable whenever chemotherapy is given. As with efficacy, toxicities are usually dose-dependent. Increase the dose, increase the efficacy, increase the toxicity. The success of chemotherapy depends largely on how well the relationship between efficacy and toxic side effects is resolved. The absorption, distribution, metabolism, and excretion of drugs may vary among individuals, and each person should be closely observed and monitored. Toxic side effects of chemotherapy include: gastrointestinal reactions, bone marrow suppression, cardiac and pulmonary toxicity, hepatic and renal impairment, neurotoxicity, genitourinary toxicity, skin and mucous membrane damage, local irritation, phlebitis, allergy, and others. The majority of adverse reactions are gastrointestinal reactions and myelosuppression. Bone marrow suppression is characterized by a decrease in the hematopoietic capacity of the bone marrow. Bone marrow suppression is often the most significant dose-limiting toxicity of chemotherapy. Some adverse reactions are related to specific drugs, such as urinary tract irritation and hemorrhagic cystitis due to CTX and IFO, pulmonary toxicity caused by bleomycin, neurotoxicity due to vincristine analogs, nephrotoxicity and high-frequency hearing impairment due to cisplatin, and possible allergic reactions due to L-mendoacetylampholytic enzymes, bleomycin, and zymosanes. Reproductive toxicity is an important long-term toxicity, alkylating agents have the most damaging effect on the testes, CTX can affect sperm maturation, causing sperm reduction or lack of sperm, leading to infertility.DDP also has a large effect on the testes, which is damaged in a dose-dependent manner. Permanent ovarian hypoplasia and amenorrhea occur in at least half of female patients treated with alkylating agents. Adverse effects of chemotherapy, in mild cases, can affect the patient’s quality of life either chronically or temporarily, limit the dose and duration of chemotherapy, affect the efficacy of the treatment, and in severe cases can be life-threatening. Easier to deal with: myelosuppression, gastrointestinal reactions; more difficult to deal with neurotoxicity, myocardial injury, liver and kidney function damage. I. Myelosuppression 1. Granulocytopenia The hazards of granulocytopenia are: 1). Forced reduction or discontinuation of chemotherapy; 2). Causes the most significant recent danger of predisposing to serious infections; 3). The chance of serious bacterial infections is significantly increased if white blood cell values below 1.0 x 109/L persist for more than 5 days. The types of granulocyte colony-stimulating factor (G-CSF, GM-CSF) are: G-CSF: Wheeler Blood, Granocet, Giselle, Rheumatoxin, Rheoblastic, Gemfen, and many others; GM-CSF: Unifen, Terlip, Gemcine, and so on. Dosage: G-CSF 2-5 micrograms/kg/d, GM-CSF 5-10 micrograms/kg/d, subcutaneous injection; start 24-72 hours after chemotherapy, granulocytes fall to the lowest point and then rise ≥ 10.0 × 10 9 / L when the drug is discontinued, generally used for about 5 days, monitoring the blood picture. Special Note: G-CSF should not be used within 24 hours before or after chemotherapy. Granulocyte colony-stimulating factor adverse reactions: bone pain, fever, malaise, headache, muscle pain, rash, pain at the injection site. Rare side effects: hypotension, nausea, diarrhea, edema, hypersensitivity, capillary leakage syndrome, dyspnea. Principles of prophylactic application of G-CSF: 1. Prophylactic use of G-CSF is not recommended in patients who are first treated; 2. Prophylactic use of CSF may be considered if neutropenia occurs in the previous cycle of chemotherapy or if severe and prolonged granulocytopenia occurs, leading to significant downward adjustments of chemotherapy dosage or postponement of chemotherapy; 3. Factors of high-risk of infection may be considered. 2. Thrombocytopenia Theoretically, when PLT<50×10 9, there will be bleeding risk; when PLT<20×10 9, the risk of bleeding increases; PLT<10×10 9 is prone to life-threatening central nervous system hemorrhage, gastrointestinal hemorrhage and respiratory hemorrhage. Clinically, it is not rare to cause serious bleeding complications. Those with bleeding tendency should be given platelet transfusion, hemostatic drugs; those without bleeding tendency, if PLT>20×10 9, can be given bed rest, avoid bumping and observe the condition; in order to ensure that the next time on time chemotherapy, when platelets drop to 50×109, can be given platelet growth factors, the types are: recombinant human thrombopoietin (rhuTPO TBio), interleukin-11 ( Giant and granulocyte, Mygel), GM-CSF (Unifen) and so on. Tebio started 24 hours after chemotherapy, 300U/(kg/d) iH for 14d, platelet count recovered to more than 100×10 9, or absolute platelet count increased ≥50×10 9 Interleukin-11 dosing regimen: therapeutic dosing: when PLT is 20-50×10 9, 25.0μg/(kg/d ) for 14 days; when PLT is 50-1 million, 12.5 μg/(kg/d) for 7 days; discontinue when PLT ≥100×10 9. Prophylaxis: 12.5-25.0 μg/(kg/d) administered 24 hours after the end of chemotherapy; the number of days of administration was determined by platelet count. Interleukin-11 adverse reactions: water and sodium retention: peripheral edema, severe may have pleural fluid, ascites, pericardial effusion; cardiovascular: arrhythmia, tachycardia, atrial fibrillation; injection of local: redness, swelling, pain; other: fatigue, rash, anorexia, allergy 3, erythrocytopenia The dangers of erythrocytopenia are fatigue, immune function defects, induction of drug resistance and tumor progression, affecting long-term survival. Red blood cell reduction Hb <8g when transfusion of red blood cell suspension; ASCO treatment guidelines: Hb ≤ 10g when using recombinant human erythropoietin rhEPO (Ebio); so that the maintenance of Hb at 12g level. Ebio usage: 10,000IU tiw.iH, currently commonly used 30,000IU once a week for 12-16 weeks. Generally about 4 weeks after the drug appeared obvious efficacy, at the same time pay attention to iron supplementation: intravenous iron supplementation is the best (such as iron sucrose, Moritigenin). Side effects of Ebio: patients with a history of hypertension may aggravate the condition; long-term application, increase the chance of thrombosis, especially those with a history of thrombosis. II. Gastrointestinal reactions 1. Vomiting Types of vomiting: 1). Acute vomiting: occurs within 24 hours after chemotherapy, the severity depends on the degree of vomiting caused by chemotherapy drugs and the dose. 2). Delayed vomiting: occurs after 24 hours of chemotherapy and tends to last for 2-4 days, most pronounced with DDP, also common with regimens containing IFO, CTX. 3). Anticipatory vomiting: mostly caused by conditioned reflexes: e.g., severe vomiting after multiple previous courses of chemotherapy, hospital environment, smells, sounds, etc. The most effective inhibitors of vomiting are 5-HT3 receptor antagonists, the types of which are: endansetron, granisetron, tropanexetron, azasetron, ramosetron. 5-HT3 receptor antagonists + corticosteroids are preferred for high- and intermediate-risk acute vomiting; low-risk patients can use any of the above single agents. For delayed vomiting, 5-HT3 receptor antagonist is less than 50% effective, can be used gastroparesis 10mg + dexamethasone 1.5mg.Q6h oral. Anticipatory vomiting, control vomiting due to first chemotherapy; anxiolytic. Severe vomiting can be given tranquilizers such as Valium and Finagan. 2, constipation The beginning of chemotherapy should prevent constipation, due to the toxic side effects of drugs or antiemetic drugs, it is very easy to cause constipation, and in severe cases, it can cause intestinal obstruction. Treatment of constipation commonly used drugs: DuMeiKe, MaRenLun intestinal, laxative, etc. or senna leaf water drink. If there is no stool > 3 days, need to be given to the Keseru or enema to promote its defecation (usually with 300-500ml of soapy water). 3, oral mucositis, ulcers Prevention and treatment: eat more fresh vegetables, fruits; vitamin C, vitamin B (available long-acting riboflavin 100mg); pay attention to oral hygiene: salt water gargle, mouth Thai gargle, Qing Xin gargle. 4, loss of appetite to improve appetite medications are Jia Di (megestrol) 320mg Bid po or Progesterone 500mg Bid po, while oral aspirin 100mg Qd to prevent thrombosis. Progestogens should not be used for too long (generally not more than 2 weeks), so as not to increase the chance of thrombosis III. Other common side effects Due to the side effects of DDP on the kidneys, large doses of DDP need to be hydrated for three consecutive days to protect the kidneys. The hydration dose is about 2500-3000ml/d, and the elderly pay attention to the cardiac function. Generally 1500ml of fluid before and after DDP, dehydration with mannitol after DDP, and tachycardia 20mg.iv. diuresis can be given at the end of infusion. For the elderly, renal function is a little poor, can be given atomolan 1.5g/m2 ivgtt before DDP to protect renal function. Certain specific toxicity prophylaxis: hemorrhagic cystitis prophylaxis due to IFO, CTX: sodium mesylate; antidote therapy for HD-MTX: calcium aldehyde hydrofolate.