Toxic reactions of antineoplastic drugs can be divided into two categories: immediate toxic reactions and long-term toxic reactions. Recent toxic reactions generally refer to those occurring within 4 weeks after drug administration, and can be divided into two categories: local reactions and systemic reactions. The local reactions of antineoplastic drugs are mainly caused by local leakage of antineoplastic drugs, causing tissue reaction or necrosis and embolic phlebitis, which are related to the tissue irritation of some antineoplastic drugs. According to the different irritation of tissues, antitumor drugs can be divided into three categories: strong irritant drugs, obvious irritant drugs and non-obvious irritant drugs. Among the commonly used chemotherapeutic drugs, those with strong irritation include: actinomycin D, doxorubicin, erythromycin, mitomycin C, nitrogen mustard, puccamycin, vincristine, vincristine, vincristine amide, vincristine, etc.; the drugs with obvious irritation include: carmustine, dacarbazine (azulfiram), etoposide, teniposide, doxorubicin, mitoxantrone, paclitaxel, etc. Once extravasation is suspected to occur, take: ① Stop the infusion. (ii) Restrict movement of the limb. ③Pump back the extravasated drug. ④Extract the needle. ⑤ Avoid applying pressure at the site of extravasation. (6) Use local antidotes according to different drugs when indicated. (7) Apply cold or hot compresses locally according to different drugs. ⑧Elevate the limb. ⑨Report and record. ⑩Topical use of Chinese herbal medicine or magnesium sulfate topical application. Many antineoplastic drugs can cause embolic phlebitis, such as nitrogen mustard, doxorubicin, actinomycin D, fluorouracil, cytarabine, azulenimide, teniposide, vincristine, vincristine, etc., with nitrogen mustard and vincristine being more prominent. Prevention is better than cure in the management of phlebitis. The drugs should be diluted to a certain concentration, the drip rate should be adjusted when dripping, and it is meaningful to choose deep or central venous placement. The use of PICC has a very good preventive effect on preventing drug extravasation. Systemic reactions 1. Allergic reactions The drugs that are more prone to allergic reactions are doxorubicin, paclitaxel, etoposide, teniposide, bleomycin, doxorubicin, levomeperidine, cisplatin and so on. Oxaliplatin has also been reported to cause anaphylactic reactions, which generally occur after a median of seven courses of therapy. Allergic reactions can be classified as local or systemic. Local anaphylactic reactions are manifested by the appearance of wind clusters, urticaria or erythema along the veins, commonly seen with doxorubicin and epirubicin, and can be continued if they subside after intravenous administration of hydrocortisone or saline, but should be slow. Symptoms or signs appearing within 15 min after the start of drug administration should be regarded as systemic allergic reactions, which can be manifested as facial redness, urticaria, hypotension, cyanosis, etc. The infusion should be stopped immediately and treated accordingly. Typical type I allergic reactions occur mostly within 1h after drug administration, but can also occur within 24h after exposure to the drug. Prophylactic anti-allergic drugs are required before the use of paclitaxel and doxorubicin. Prophylactic antiallergic treatment of paclitaxel: dexamethasone 20mg, orally 12h and 6h before administration; benadryl 50mg, intramuscularly 30min before treatment; cimetidine (mecamylamine) 300mg, intramuscularly 30min before treatment. Dexamethasone 7.5mg twice daily is required 1 day before, the day of and 1 day after doxorubicin application to control allergic reactions and sodium water retention. Monoclonal antibody drip with drip-related reactions, such as flushing, chest tightness, dyspnea, etc. The drip rate should be strictly controlled and dexamethasone, isoproterenol (finasteride), indomethacin (anti-inflammatory pain), etc. should be given appropriately, which can reduce drip-related reactions. Fever Excessive fever caused by bleomycin is a rare and unusual direct release of pyrogen in sensitive individuals. Patients with lymphoma are more sensitive because they have disease-related fever. Serious consequences can be avoided if a low dose (1 mg) is tested, temperature and blood pressure are closely monitored, fluids are rehydrated, and antipyretics and hormones are used. Chemotherapeutic drugs known to cause febrile reactions include actinomycin D, doxorubicin, nitrogen mustard, puccamycin, azulenimide, levomethalin, high-dose methotrexate, cytarabine, etc. Most cytokines and monoclonal antibodies can also cause febrile reactions. 3. Hematopoietic system reaction Due to the different half-life (120d for erythrocytes, 5~7d for platelets, 4~6h for leukocytes), initially it often shows a decrease in leukocytes, especially granulocytes, followed by a decrease in platelets, and in severe cases, hemoglobin is also reduced. Nitrosoureas, leucovorin and gemcitabine predispose to thrombocytopenia. Only a few drugs have no or little myelosuppression, including corticosteroids, bleomycin, levomucoidase, and vincristine. Interferon and tamoxifen (triamcinolone) can also cause leukopenia, but it is mostly not severe. The degree of myelosuppression caused by antineoplastic drugs is closely related to the individual patient’s bone marrow reserve capacity. Patients with liver disease, hypersplenism, radionuclide irradiation or past radiotherapy (especially those with significantly low white blood cells or platelets) are more likely to have significant myelosuppression. Most chemotherapy-induced myelosuppression recovers 2 to 3 weeks after discontinuation of the drug, but cetepe, nitrosoureas, mitomycin C and azelaic acid phenylpropionate have delayed myelosuppression, and recovery takes more than 6 weeks. Management of anemia: ①Check hemoglobin, red blood cells and hematocrit regularly. ②Transfusion of red blood cell component blood if anemia is severe. ③Treat those with bleeding tendency. ④Oxygen intake if necessary. (⑤Pay attention to rest if there is obvious vertigo and weakness. (6) Give erythrocyte growth factor (EPO). Treatment of leukocyte/granulocytopenia: ①Check the total leukocyte count and granulocyte count before and after chemotherapy, once or twice a week, and increase it when it decreases significantly until it returns to normal. ②G-CSF should be given if necessary. ③In severe cases, reduce the chemotherapy dose or stop the drug. ④Pay attention to measures to prevent infection. ⑤ Give antibiotics if necessary. Treatment of thrombocytopenia: ①Check the platelet count before and after chemotherapy, once or twice a week, and increase it when it is obvious until it returns to normal. ② Pay close attention to bleeding tendency. ③Avoid the use of drugs with anticoagulant effect. ④Prevent the occurrence of bleeding by avoiding forceful nose blowing, cautious tooth brushing, shaving with electric whiskers, minimizing traumatic operations, injecting holes with forceful and prolonged pressure, and women need to pay attention to menstrual bleeding and postpone menstruation with drugs if necessary. ⑤ If the platelet count is too low, single-collection platelets should be transfused when available. (6) Platelet growth factor, interleukin-11 and other drugs have a certain effect of raising platelets. (7) Give hemostatic drugs to prevent bleeding. 4.Gastrointestinal reaction: It is the most common adverse reaction of chemotherapy. (1) Loss of appetite: It is the initial reaction of chemotherapy, which occurs 1~2d after chemotherapy, and generally no special treatment is needed. Progesterone drugs can help improve appetite. (2) Nausea and vomiting: There are generally three types of vomiting caused by chemotherapy. Acute vomiting refers to vomiting that occurs within 24h after chemotherapy. The vomiting that occurs after 24h to 5~7d after chemotherapy is called delayed vomiting. Another type of vomiting, similar in nature to conditioned reflexes, is vomiting that occurs after the patient’s previous chemotherapy has caused significant acute vomiting and before the subsequent chemotherapy, called pre-emptive vomiting. Generally, oral administration of lomustine (cyclohexylnitrosourea), procarbazine (methylbenzylhydrazine) and other drugs or sedative injection of nitrogen mustard, cisplatin, dacarbazine, doxorubicin and other drugs trade cause obvious nausea and vomiting. The main drugs currently used for antiemetic are 5-HT3 receptor antagonists, metoclopramide, dexamethasone, and chlorpromazine. Currently, 5-HT3 receptor antagonists are commonly used alone or in combination with dexamethasone, and sedative drugs such as diazepam (Valium) and chlorpromazine can be added. Antiemetic drugs used to treat acute nausea and vomiting caused by chemotherapy drugs are often ineffective for the treatment of pre-emetic vomiting. Should be taken to relax and ease the psychological treatment methods, or depending on the situation to anti-anxiety or antidepressants. (3) Mucositis: During cancer treatment, 40% of standard chemotherapy patients and 60% of bone marrow transplant patients may have oral mucositis, 50% of which require treatment. Direct oral toxicity usually occurs 5-7 d after chemotherapy, with antimetabolic and antibiotic drugs, often first seen at the junction of the buccal mucosa and mouth and lips. Patients who are debilitated and immunosuppressed are susceptible to secondary fungal infections. High doses of fluorouracil given can produce severe mucositis with bloody diarrhea, even life-threatening. If severe mucosal reactions and granulocyte deficiency occur early after administration, the patient should be suspected of having dihydrofolate reductase deficiency and fluorouracil should be discontinued immediately and prohibited from future use. The management of stomatitis is: ① Continuous and thorough oral care, rinsing the mouth with a solution of compounded borax, 3% sodium bicarbonate or 3% hydrogen peroxide, often especially after eating. The presence of fungal infection is mostly accompanied by white spots or white film, and should be gargled with mycotoxin solution or topical application of drugs containing mycotoxin. Oral ulcers can be coated with Chinese medicines such as bingbao, pearl or tin. ②Reasonable adjustment of food. A highly nutritious liquid or diet equivalent to room temperature should be fed, avoiding irritating foods. When pain is obvious in the acute phase, antihistamines or indicated anesthetics such as procaine or lidocaine can be used for pain relief 15~30min before eating. (3) Strengthen supportive treatment and correct water, electrolyte and acid-base imbalance. (4) Diarrhea: Diarrhea caused by chemotherapy drugs is most commonly caused by antimetabolites, such as fluorouracil, methotrexate and cytarabine. Others that cause diarrhea are actinomycin D, hydroxyurea, erythromycin, irinotecan, nitrosoureas, paclitaxel, gefitinib, sorafenib, etc. With the widespread use of biological agents, alpha interferon and interleukin-2 have been found to cause diarrhea as well. High-dose chemotherapy regimens using stem cell transplantation can also be associated with severe diarrhea. Delayed diarrhea due to irinotecan is defined as diarrhea that occurs 24 h after the end of irinotecan chemotherapy, with a median occurrence of 5-7 d, but may occur throughout the chemotherapy interval. Once delayed diarrhea occurs, 2 tablets of loperamide (Emmonstop) with plenty of fluids should be given immediately, followed by 1 tablet of loperamide every 2h until the last loose stool and continued for 12h, up to 48h, to avoid paralytic intestinal obstruction. It is worth noting that loperamide should not be applied prophylactically. If diarrhea persists for more than 48h according to the above treatment, prophylactic oral broad-spectrum antibiotics should be started and extra-gastric supportive therapy should be given, while other anti-diarrheal treatments, such as growth inhibitor octreotide, should be switched. Irinotecan can also cause acetylcholine syndrome, which is defined as lacrimation, sweating, hypersalivation, blurred vision, abdominal pain, and diarrhea within 24h after drug administration. Atropine 0.25mg subcutaneously can be given therapeutically, and acetylcholine syndrome can be prevented with atropine 0.25mg subcutaneously before the next treatment. Treatment: ①Eat a low-fiber, high-protein diet with adequate fluids. ②Avoid drugs that irritate the gastrointestinal tract. ③Rest more. ④Antidiarrheal drugs. ⑤Add fluids and electrolytes intravenously if necessary. ⑥The number of diarrhea is more than 5 times a day or bloody diarrhea should be discontinued with relevant chemotherapy drugs. Recently, octreotide has been found to be often effective in controlling drug-induced diarrhea and diarrhea associated with carcinoid syndrome. Checking peripheral blood leukocyte count should not be neglected in patients with diarrhea. (5) Constipation: The use of neurotoxic chemotherapeutic drugs may lead to constipation, and these drugs include vinca alkaloids (vincristine, vincristine, vincristine amide, vincristine), etoposide, cisplatin, and others such as doxorubicin and mitoxantrone have also been reported. Vinca alkaloids, especially vincristine, are the most prominent and can occasionally cause paralytic intestinal obstruction, necessitating a reduction in dosage for patients of advanced age. Treatment: ①Eat a fiber-rich diet, fresh fruits and vegetables, and consume adequate fluids. ②Laxatives to soften stools. ③Control the frequency of using 5-HT3 receptor antagonists. ④If necessary, take abdominal radiographs to understand the intestinal condition. (6) Gastrointestinal perforation: Gastrointestinal perforation due to bevacizumab has been reported to be disease-related. The incidence is highest in patients with bowel cancer, about 10%; ovarian cancer is the second highest, 1.5%~3%; while the incidence is low in breast cancer and lung cancer. (7) Pancreatitis: such as when using levomepromactinase, gefitinib, lomustine, etc. are more common. (8) Hyperglycemia: such as the use of streptozotocin, levomentoside enzyme is more common 5, skin and appendages (1) Photosensitivity: Actinomycin D, methotrexate, fluorouracil, bleomycin and doxorubicin can cause an increase in skin sensitivity to sunlight, and acute sunburn and unusual darkening of the skin occurs after slight exposure. (2) Hyperpigmentation: Many drugs can cause darkening of the skin, partly due to sensitivity to sunlight. Drugs that fall into this category include actinomycin D, leucovorin, cyclophosphamide, fluorouracil, doxorubicin, bleomycin, methotrexate, and thiopurine. (3) Recall reaction: Patients who had radiation treatment and had radiation dermatitis in the past may have changes similar to radiation dermatitis again after using actinomycin D. This becomes “recall reaction”. Later, it was found that fluorouracil and doxorubicin also cause “recall reactions”, including acute erythema and skin pigmentation. (4) Nail deformation: such as the use of bleomycin, doxorubicin, fluorouracil, doxorubicin, hydroxyurea, etc. (5) Rash: Bleomycin, azelaic acid benzoate, paclitaxel doxorubicin, zolpidemidine, desoxorubicin, hydroxyurea, lomustine, actinomycin D, cyclophosphamide, fluorouracil gemcitabine, gefitinib, erlotinib, cetuximab, etc. are more common and can mostly disappear after stopping the drug. Pemetrexed requires dexamethasone 4mg twice daily 1 day before, the day of, and 1 day after application to prevent skin reactions. Rashes caused by targeted drugs have received increasing attention in recent years. This type of rash is usually mild to moderate, positively correlates with the efficacy of the targeted drug, and can be controlled by suspension of the drug or dose reduction. The rash may also resolve with continued use of the targeted drug. If only dry skin is present, moisturizer and petroleum jelly may be used. Sun exposure may aggravate the rash and should be avoided. There is no standard treatment; potentially effective drugs include hormonal ointments, topical immunomodulators, and topical retinoic acid ointments. If pruritus is present, antihistamines may be used; if infection is present, topical topical or oral antibiotics are considered. If local necrosis, blistering, petechiae, petechiae, purpura or skin lesions not associated with rash appear, consult a dermatologist. (6) Alopecia: Anthracyclines and botanicals are the most obvious. Hair loss usually occurs 2~3 weeks after the first dose of chemotherapy and grows back gradually 6~8 weeks after the cessation of chemotherapy and should be explained to the patient in advance. The use of special ice caps during the administration of drugs has been reported to have some preventive effect. (7) Nail fungus: common with the use of gefitinib and cetuximab, for example. (8) Hand-foot syndrome: Capecitabine and sorafenib are the most pronounced, and doxorubicin has also been reported. Some literature reports celecoxib (celecoxib) and vitamin B6 have some preventive effect. 6. Cardiotoxicity Cardiotoxicity caused by anthracycline anticancer drugs, the incidence of which is related to the cumulative dose. The incidence is 5% for doxorubicin 450mg/m2, erythromycin 900mg/m2, epirubicin 935mg/m2, and desmethyl erythromycin 223mg/m2; 30% for doxorubicin >600mg/m2 and about 50% for >1000mg/m2. Mediastinal radiotherapy, >70 years or <15 years, coronary artery disease, other valve and cardiomyopathies, and hypertension are risk factors. High doses of cyclophosphamide and isocyclophosphamide can cause congestive heart failure; high doses of fluorouracil can cause coronary artery spasm; bevacizumab can cause hypertension and congestive heart failure and can cause arterial and venous embolism; and sorafenib can cause cardiac ischemia and myocardial infarction. Prevention of anthracycline-induced cardiotoxicity: ①The cumulative dose of doxorubicin should generally be less than 550 mg/m2. ②The cumulative dose should not be more than 450 mg/m2 for those who are old (>70 years old), have pre-existing heart disease, have had radiotherapy to the mediastinum or have been treated with high-dose cyclophosphamide, so controlling the cumulative dose ≤500 mg/m2 is an effective measure to prevent cardiotoxicity. The cumulative dose of mitoxantrone should be less than 140 mg/m2. ③The cumulative dose of epirubicin should be less than 1100 mg/m2. ⑤ Use liposomal doxorubicin. (6) When combined with paclitaxel, the interval between the two should preferably be 4 to 24 h. (7) In patients with risk factors, monitor LVEF for every 200 mg/m2 increase in doxorubicin accumulation. Risk factors for cardiotoxicity of gancizumab (Herceptin) are age >60 years and combination chemotherapy, especially concomitant use of anthracyclines. Other suspected risk factors include total anthracyclines ≥400 mg/m2, receipt of chest wall radiotherapy, and pre-existing cardiac insufficiency. Most of the cardiotoxicity due to ultrastuzumab is mild and nonspecific, most often manifesting as asymptomatic reduction in LVEF, with less frequent occurrence of grade III-IV cardiac insufficiency. However, the cardiotoxicity of anthracyclines and griseofulvin differs significantly in two aspects: first, cumulative dose correlation, where anthracycline-induced cardiotoxicity is related to cumulative dose, whereas griseofulvin-related cardiotoxicity is not related to dose; and second, reversibility, where the former tends to be irreversible and the latter results in symptomatic improvement, improved cardiac function, and elevated LVEF in most patients with standard therapy or discontinuation of use. In some patients, it can be continued after recovery of cardiac function. Measures to prevent the cardiotoxicity of gonslizumab: ① Avoid the use of gonslizumab in patients of advanced age. (ii) Avoid combination chemotherapy regimens with groupizumab and anthracycline-containing drugs. ③If anthracyclines are used. The anthracycline-containing regimen (total doxorubicin should be ≤400~450 mg/m2) can be used first, followed by gancizumab, and monitored closely. Anthracycline therapy should be avoided for 22 weeks after stopping treatment with griseofulvin. ④Use liposomal doxorubicin or other less cardiotoxic anthracyclines such as epirubicin. ⑤ Use only when the LVEF is normal. 7.Pulmonary toxicity: Bleomycin is the drug most likely to cause pulmonary toxicity. The first clinical manifestation is the decrease of lung volume and diffusion function, followed by some patients’ chest X-ray showing interstitial exudation at the base of both lungs, which is diffuse or cornified. The cumulative dosage should not exceed 300 mg. It should be used with caution or not in patients with advanced age (>70 years), chronic lung disease, poor lung function, and previous lung or mediastinal radiotherapy. Pulmonary function and chest radiographs should be reviewed every 3 months during dosing. Pulmonary toxicity of carmustine may manifest as chronic damage occurring in the distant future or as acute reversible syndromes. Clinically, pulmonary edema and acute respiratory distress syndrome are characteristic, and most have pulmonary symptoms at cumulative doses up to 1200-1500 mg/m2; 50% have definite toxicity at cumulative doses >1500 mg/m2. Bactrim can cause symptomatic lung disease and intra-alveolar fibrosis. Pulmonary toxicity of methotrexate is the most common among antimetabolites. The best protocol for managing chemotherapy-related pulmonary toxicity is prophylaxis. Once pulmonary toxicity occurs. The primary measure is to discontinue the drug and give aggressive symptomatic treatment, including oxygenation, administration of corticosteroids and antibiotics. 8. Hepatotoxicity: A series of antitumor drugs can cause hepatotoxicity, there are mainly 3 types: ① hepatocellular insufficiency and chemical hepatitis. ②Venous occlusive disease. ③ chronic liver fibrosis. In recent years rituximab (meloval) has been reported to cause hepatitis B virus activation in hepatitis B virus-positive patients, leading to severe hepatitis. Therefore, hepatitis B virus DNA particles should be tested in such patients and should be used with caution in positive patients or concomitant oral lamivudine. The main antitumor drugs that cause hepatotoxicity are: ① drugs with a high potential for hepatotoxicity: levomethalin, methotrexate (long-term), cytarabine, streptozocin, interferon (high dose). ②Drugs with high potential for high dose effects: leucovorin, actinomycin D, carmustine, methotrexate, cyclophosphamide, mitomycin C, cytarabine. ③ Drugs that occasionally cause irreversible hepatotoxicity: leucovorin (high dose), dacarbazine, carmustine (high dose), methotrexate, cytarabine, mitomycin C. ④ Drugs for which hepatotoxicity has been reported in individual cases: dacarbazine, thiopurine, hydroxyurea, interferon (low dose), vincristine. Treatment: ①Patients with chemotherapy should first obtain medical history including medication history, and use cautiously or reduce the dose of antitumor drugs, especially those with liver damage, if they have liver insufficiency. ②Liver function should be reviewed regularly during chemotherapy, including alkaline phosphatase (AKP), glutamyl transpeptidase (γ-GT) and other enzymatic measurements, which need to be differentiated from metastatic liver cancer or liver infiltration and viral hepatitis. ③In general, hepatocellular injury, especially the elevation of aminotransferase that occurs within a short period of time after drug administration, is mostly transient and can recover rapidly after drug discontinuation. If liver-protective drugs can be given, most of them can continue to receive treatment, and Chinese medicine also has certain effect. ④For the liver function damage that appears later, it should be paid attention to, and it is better to stop the drug. ⑤Dose adjustment of anticancer drugs when liver function is abnormal: when bilirubin <25μmol/L or aminotransferase <60U/L, fluorouracil, cyclophosphamide, methotrexate, erythromycin, doxorubicin, vincristine, vincristine, etoposide can be used at 100% of the conventional dose. When bilirubin 25.7~51.4μmol/L or aminotransferase 60~180U/L, fluorouracil, cyclophosphamide, methotrexate can be used at 100% of the conventional dose, and erythromycin can be given at 75% of the dose, and doxorubicin, vincristine, vincristine, etoposide can be used at 50% of the conventional dose. When bilirubin 53~86μmol/L or aminotransferase >180U/L, fluorouracil can be given 100% of the regular dose, cyclophosphamide and methotrexate can be given 75% of the dose, erythromycin can be given 50% of the dose, doxorubicin can be given 25% of the dose, while vincristine, vincristine and etoposide need to be discontinued. When bilirubin > 86 μmol/L, all the above drugs need to be discontinued. 9, urinary system reactions: urinary system effects are mainly renal damage and hemorrhagic cystitis. (1) renal damage: antineoplastic drugs that cause nephrotoxicity: ① drugs with high possibility: methotrexate, mitomycin C, cisplatin, puccamycin, streptozocin, isocyclophosphamide. ②Drugs that cause azotemia only: dacarbazine, levomepromazine. ③Drugs that occasionally cause irreversible nephrotoxicity: cisplatin, lomustine, mitomycin C, fludarabine, streptozocin. (iv) Drugs with isolated cases of reported nephrotoxicity: carboplatin, thiopurine, methotrexate (low dose). Treatment: The main focus is to prevent the development of renal damage. ①Cisplatin mainly for adequate hydration, diuresis as well as the use of combination chemotherapy to reduce the single drug dose. Amphotericin may reduce or prevent the nephrotoxicity of cisplatin. Aminoglycoside antibiotics should not be used during cisplatin chemotherapy. The level of renal function needs to be monitored before each dose, and the dose should be reduced by 25% when the creatinine clearance is <60 ml/min, and should be stopped when it is <30 ml/min. When the dosage of cisplatin is large, hydration and diuretic measures should be used to protect renal function. Hydration: More than 2000ml of intravenous rehydration fluid should be given on the day of cisplatin administration and on the 2nd and 3rd day after cisplatin administration. 1000ml of rehydration fluid should be given on the day of cisplatin administration before giving cisplatin chemotherapy. Diuresis: give 250ml of 20% mannitol before cisplatin drip and 20mg of furosemide after the end of cisplatin drip, and record 24h urine volume and urine routine. ② When using high dose methotrexate, it is appropriate to give large amount of infusion and urine alkalinization, monitor methotrexate blood concentration, and use calcium folinic acid relief therapy. ③Large intake of water is recommended when cyclophosphamide is used. ④Lomustine and methotrexate can cause glomerulosclerosis, tubular atrophy and interstitial fibrosis leading to renal failure. The clinical manifestations are slow increase of urea nitrogen and creatinine and kidney shrinkage. Preventive measures include not exceeding a cumulative total of 1500 mg/m2 and monitoring renal function and kidney size. ⑤ Oral packaged aldehyde starch can be given in mildly elevated urea nitrogen. (6) Severe uremia requires dialysis treatment. (vii) Renal injury characterized by a microvascular hemolytic process may occur with cisplatin or mitomycin. The onset is acute and manifests as hemolytic anemia, peripheral blood smear with erythrocyte fragments, hematuria and proteinuria may be present, and renal insufficiency develops 1 to 2 weeks after the onset. Discontinuation of relevant drugs and rapid plasma exchange can restore renal function. It is worth mentioning that blood transfusion can promote or aggravate microvascular hemolytic anemia and should be avoided as much as possible. (2) Hemorrhagic cystitis: Cyclophosphamide can cause aseptic chemical cystitis, which is related to the direct stimulation of the bladder mucosa by acrolein, a metabolite of cyclophosphamide. The drug should be rehydrated in adequate amounts at higher doses, and long-term users should have their urine routinely rechecked. Cystitis should be discontinued when it occurs, and its use should be avoided in the future if possible. The principle of chemical cystitis caused by isocyclophosphamide is the same as that of cyclophosphamide. It can be largely prevented by the use of sodium mercaptansulfonate. High doses of cyclophosphamide can also be administered with sodium mercaptosulfate. (3) Bevacizumab can cause proteinuria and, in severe cases, nephrotic syndrome. 10. Neurological reactions: antineoplastic drugs that cause neurotoxicity: (1) Drugs with a high probability of: levomendanase, interferon (high dose), thalidomide, carboplatin, isocyclophosphamide, vincristine, cisplatin, methotrexate, vincristine, cytarabine, platinum oxalate, vincristine, doxorubicin, paclitaxel, procarbazine, fluorouracil. ② Occasional irreversible neurotoxicity: cisplatin, fluorouracil (in combination with levamisole), methotrexate (intrathecal injection), cytarabine, isocyclophosphamide, paclitaxel, doxorubicin. Drugs acting on microtubules mainly cause peripheral neurotoxicity, which is dose-dependent and usually recovers after discontinuation of the drug. The treatment of neurotoxicity with cisplatin is discontinuation of the drug, and amphotericin has a protective effect. Cisplatin can also cause tinnitus and high-frequency hearing loss, occurring in up to 11% of cases, and can cause deafness in severe cases. Cerebellar ataxia can occur with isocyclophosphamide and fluorouracil. Peripheral sensory nerve abnormalities caused by platinum oxalate include acute and cumulative symptoms. Acute symptoms manifest as dullness and/or abnormal sensation of the extremities and/or perioral area, and occasionally reversible acute pharyngeal sensory disturbances, usually mild, which can occur within minutes of infusion and recover spontaneously within minutes to hours or days, and can be provoked or exacerbated by cold or exposure to cold objects. Therefore, during treatment, patients should be advised to avoid cold food, cold drinks, and contact with cold water or other cold objects. In addition, the duration of intravenous infusion should be extended from 2h to 6h in subsequent courses of treatment to prevent recurrence of symptoms. Oxaliplatin is mainly a dose-related, cumulative, reversible peripheral neurotoxicity, mainly manifested as dullness and/or abnormal sensation in the limbs, which can be induced or aggravated by cold, especially at cumulative doses of 850 mg/m2 or more, with an incidence of 82%, of which 12% may develop functional impairment. It can be recovered several months after stopping treatment, and gradually recovered on average 12~13 weeks after discontinuing the drug. 11. Bleeding and coagulation disorders: puccamycin and levomucoidase are the most likely to cause, bevacizumab can cause bleeding and delayed wound healing, gefitinib can cause nasal bleeding, imatinib can cause bleeding from tumor tumor, and surgery is required in severe cases. Treatment: ①Puccamycin-induced coagulation disorder, change the daily dose to every other day, the incidence is greatly reduced. ②Replenish platelets and red blood cells. ③Bevacizumab is contraindicated in patients with bleeding tendency or who are on anticoagulant drugs, and do not operate 28d before and after using bevacizumab. 12. Immunosuppression: Many antitumor drugs including adrenocorticotropic hormones are immunosuppressive, cyclophosphamide, mercaptoguanine, levomeperidine and cortisone are the most obvious. Usually, the immune function can be normalized within 6 months after the completion of treatment. The more common ones are growth retardation, sterility, immunosuppression, liver fibrosis, nerve damage and a second primary malignancy. 1. Gonads: The effects of chemotherapy on the gonads may be prolonged and in many cases lead to complete destruction of reproductive capacity. It usually produces gonadal insufficiency in men and causes premature gonadal failure in women. Amenorrhea often occurs with the application of the alkylating chemotherapeutic agents leucovorin, nitrogen mustard phenylbutyrate and cyclophosphamide, as do procarbazine and vincristine. Ovarian hypofunction is reversible, and menstruation begins to return to normal after discontinuation of the drug. Patients may become pregnant, but there may be an increased risk of fetal malformations. Both azadirachtin benzoate and cyclophosphamide can cause testicular damage, resulting in sperm deficiency and failure to find germ cells on testicular biopsy, which is irreversible in some men. The hormone-producing germ cells are less affected by the drug, so the effects on pubertal development and secondary sexual characteristics are smaller than the effects on fertility. 2, bone: methotrexate for leukemia maintenance treatment in some patients with non-tumor-related fractures, osteoporosis and bone pain, and ischemic necrosis of the femoral head 1-2 years after MOPP and COPP regimen chemotherapy have been reported in several cases. 3. Second primary malignancy (SM): the incidence can be 6%~15% after effective treatment, which is 20~30 times more than the expected incidence. It occurs 1 to 20 years after treatment, with a peak seen in 3 to 9 years. The combination of chemotherapy and radiotherapy can increase the incidence of SM.