1. Indications for chemotherapy
1.1 Tumors with good efficacy mainly treated by internal medicine and can reach radical cure: such as trophoblastic cell tumors, testicular tumors, lymphoma, acute and chronic leukemia, small cell lung cancer, multiple myeloma, etc.
1.2 Solid tumors that have disseminated and multiple metastases: such as breast cancer, non-small cell lung cancer, colorectal cancer, ovarian cancer, and head and neck tumors.
1.3 Cancerous pleural, abdominal and pericardial effusion.
1.4 Superior vena cava compression signs, airway obstruction, and increased intracranial pressure due to certain cancers: chemotherapy can be given first to relieve symptoms, and radiation therapy can be given later.
1.5 Tumors that can be operated after primary chemotherapy: ovarian cancer, bone and soft tissue sarcoma, small cell lung cancer, anal cancer, bladder cancer, testicular tumor, stage III breast cancer and stage IIIA lung cancer, etc.
1.6 adjuvant chemotherapy after radical surgery (adjuvant chemotherapy) breast cancer, colorectal cancer, gastric cancer, lung cancer, soft tissue sarcoma, nephroblastoma, etc.
1.7 Tumors for which intra-arterial (interventional) chemotherapy can improve the efficacy: liver cancer, liver metastasis cancer, kidney cancer.
2.Cautions for chemotherapy
2.1 Chemotherapeutic drugs are generally not used as diagnostic treatment, and should not be used as placebo to avoid unnecessary losses to patients.
2.2 The diagnosis must be clear before starting treatment. Leukemia, multiple myeloma and malignant histiocytosis must be confirmed by hematology. Malignant lymphoma and various other solid tumors must be diagnosed by local histopathology. The examination of decidual cytology can not only clarify the diagnosis but also guide the selection of chemotherapeutic drugs.
2.3 Patients in good general condition with normal blood and liver and kidney functions should be treated with chemotherapy only.
2.4 After determining the use of chemotherapy, a specific treatment plan should be formulated to select the appropriate drug, combination, dose, route, method and course of treatment. Do not use the drug for a long time or blindly increase the dose. Closely observe the effect and toxicity of the drugs during treatment and give appropriate treatment.
2.5 During the course of chemotherapy, the blood picture should be checked on a regular basis, one to two times a week. If the blood image decreases should be observed more closely, detecting the change of blood image at any time and taking certain measures.
2.6 Long-term follow-up after the course of treatment to observe the length of the remission period and long-term toxicity.
3.Contraindications to chemotherapy
It is generally believed that chemotherapy should be used with caution or not when the patient has the following conditions.
a) Old and frail or cachectic patients;
b) previous multiple courses of radiotherapy or chemotherapy and the blood picture is very low for a long time or have a tendency to bleed;
c) Those with liver dysfunction and serious cardiovascular disease;
d) Anemia, nutritional disorders and low plasma protein;
e) Patients with bone marrow metastases;
f) patients with adrenal cortical insufficiency;
g) Patients with infections, fever and other complications;
h) Patients with cardiomyopathy should be careful not to use adriamycin, erythromycin and metal-based anticancer drugs;
i) Bleomycin and Pingyangmycin should be prohibited in patients with chronic bronchitis in the elderly.
4.Discontinuation indicators of chemotherapy
In the process of chemotherapy, if the following conditions are found, the drug should be discontinued and closely observed, and appropriate treatment or resuscitation should be given according to the situation and development trend.
a, the use of drug time exceeds the general effectiveness of the time, or the accumulated dose exceeds the possible effective dose, the chance of continued use of drugs is not very effective;
b. When frequent vomiting affects the patient’s feeding or electrolyte imbalance;
c. When diarrhea exceeds 5 times a day, or when there is bloody diarrhea;
d. When the blood picture decreases (e.g., white blood cells below 2000-3000/mm3, platelets below 50,000-80,000/mm3); sometimes it is found that the blood picture decreases sharply, and even if it does not reach this level, the drug should be stopped in time for observation to avoid serious bone marrow suppression;
e. Patients with infectious fever and body temperature over 38℃ (fever caused by tumor is not included in this case);
f. Complications;
g.The appearance of toxicity of important organs such as myocardial damage, toxic hepatitis, toxic nephritis or cystitis, chemical pneumonia or fibrosis, etc.
5.Common adverse reactions and dose adjustment
Most of the existing chemotherapeutic drugs, while inhibiting the growth or killing tumor cells, have toxic effects on the rapidly proliferating normal cells in the body, especially the bone marrow hematopoietic cells and the mucosal epithelial cells of the gastrointestinal tract, which are often the main obstacles to improve the efficacy of chemotherapeutic drugs. Inadvertent overtreatment can lead to patient death. Therefore, it is important to be highly alert to the possible toxicity when using chemotherapy, otherwise it will cause irreparable evil results.
Table 1 lists the recent toxicity of commonly used anticancer chemotherapeutic agents. Tables 2 and 3 show the dose adjustment of commonly used anticancer drugs when bone marrow suppression and liver and kidney function impairment occur during treatment, respectively. Table 4 shows the long-term toxic effects of anticancer drugs, please refer to Appendix 2 for the grading criteria.
Table 1 Recent toxicity of commonly used anticancer chemotherapeutic drugs
Immediate toxicity Immediate toxicity
Drug Nausea Vomiting Other Bone marrow suppression Other
Adriamycin + + + Local irritation +++ Hair loss, mucositis, stomatitis, cardiotoxicity*
Gelsemycin + + Skin erythema ++ Mucositis, stomatitis
Bleomycin + – fever, allergic reaction – skin pigmentation, hard skin, alopecia, pulmonary fibrosis
Carazolam ++ + + +++ Liver damage, pulmonary fibrosis
Cyclophosphamide ++ + + ++ Drugged cystitis, alopecia
Azelenimide + + + ++
Zolpidem + + + Local irritation Alopecia, mucositis, stomatitis, cardiotoxicity
Ghostoside + + + postural hypotension, ++ alopecia
Local irritation
Hexamethonium + + Abdominal pain, diarrhea + Central and peripheral neurotoxicity
Fluorouracil + – Diarrhea + Pharyngitis
Cyclohexylnitrosourea + + + +++ Liver damage, pulmonary fibrosis
Azacitidine ++ ++ Local irritation +++
Table 2 Dose adjustment of commonly used anticancer drugs in case of bone marrow suppression
Drug Dose adjustment
Leukocytes ≥4000/mm3 Leukocytes 3900-2500/mm3 Leukocytes <2500/mm3
Platelets ≥120,000/mm3 Platelets 119,000 to 75,000/mm3 Platelets <75,000/mm3
Azacitidine, cyclophosphamide, adriamycin, actinomycin 100% of the recommended dose 50% of the recommended dose Discontinue the drug and check blood once a week
Bacteriocin D, simustine, dibromovirmin Dosing after return to normal
alcohol, fluorouracil, lomustine, methotrexate
mitomycin, procarbazine, spermidine
methotrexate, thiotepa, nafuridine, vincristine, vincristine amide
vincristine, vincristine amide, etoposide
Epigallocatechin, epigallocatechin, paclitaxel
Leukocytes ≥ 3500/mm3 Leukocytes 340O~2OO0/mm3 Leukocytes <2OOO/mm3
Platelets ≥100,000/mm3 Platelets 99,000-60,000/mm3 Platelets <60,000/mm3
Cisplatin, azulfiram, hexamethonium, 100% of the recommended dose 50% of the recommended dose Discontinue the drug and administer it after normalization
Vincristine
Table 3 Dose adjustment of anticancer drugs in case of hepatic and renal impairment (A, B)
A Dose adjustment in case of hepatic impairment
BPS storage % Serum bilirubin Other Dose of medication
(45′) (mg/dl) Adriamycin and other anthracyclines Other
9-15 1.2-3 (2-5)x N 50% 75%
>15 >3 >5 x N 25% 50%
*N; upper limit of normal
Other liver function abnormalities such as prothrombin time, albumin, transaminases, cholinesterase, and transpeptidase (γ-GT) should also be dose reduced. For known hepatic tumor-occupying lesions, the first dose is reduced by 50%. Other drugs include methotrexate, nitrosoureas (CCNU, BCNU, Me-CCNU), vincristine (VCR, VLB, VDS), onychotoxins (VP-16, VM-26), and azulenimide (DTIC). The dose reduction of cyclophosphamide should be proportionally less than that of adriamycin, and other alkylating agents may be preferred.
B. Dose adjustment in case of renal impairment
Creatinine clearance Serum creatinine Urea nitrogen Drug dosage
(mlmin/1.73) (mg/dl) (mg/dl) PDD MTX Other drugs
>70 <1.5 <20 100% 100% 100%
70 – 50 1.5 – 2 20 – 50 50% 50% 75%
<50 >2 >50 – 25% 50%
If serum creatinine is used as the only reference number for renal impairment, the dose should be further reduced in older patients;
2. The dose should also be adjusted for proteinuria ≥0.3g/100ml;
3. Other drugs refer to BLM, VP-16, VM-26, MEL, CTX, PCB, MMC, DTIC and HMM;
4. The table is for general reference only, and doctors must treat them differently according to patients’ conditions.
Table 4 Long-term toxicity of commonly used antineoplastic drugs
Toxicity range Target cells Pathological changes Organ dysfunction Major drugs inducing toxicity
Organ-specific
Heart Cardiomyocytes Primary cardiomyopathy Arrhythmias, cardiac failure Anthracyclines, high-dose CTX
Pulmonary Alveolar cells Fibrosis Respiratory dysfunction Bleomycin, nitrosoureas
Liver Hepatocytes Fibrosis Liver failure Methotrexate, nitrosoureas
Renal Tubular and renal atrophy, sclerosis Renal failure Nitrosoureas, cisplatin, high dose
Glomerular cells Volume carboplatin
Nervous system Anterior horn cells Axonal degeneration Neuropathy Vinca alkaloids, paclitaxel
Gonads
Systemic Germ cells Regeneration arrest or degeneration Infertility, breast feminization Alkylating agents, methylbenzylhydrazine
Immune suppression Alkylating agent, methylbenzylhydrazine
Teratogenesis Alkylating agents, antimetabolites
Tumor (including leukemia) development Alkylating agent, methylbenzylhydrazine
The long-term toxicity of chemotherapy includes infertility, immune suppression, and the development of second malignant disease, and varies with the chemotherapeutic agent used and the composition of the drugs in the combination chemotherapy regimen. Alkylating agents such as cyclophosphamide, phenylalanine nitrogen mustard, and phenylbutyrate nitrogen mustard, as well as combination regimens such as the MOPP regimen, can lead to long-term sperm deficiency or ovarian hypofunction. Reproductive function may return in some younger patients at least 2 years after the cessation of chemotherapy.