Antineoplastic drugs
1. Classification according to structure
Alkylating agent/ Antimetabolites/ Antitumor antibiotics/ Plant alkaloids/ Hormonal agents/
Others
2. Classification according to mechanism of action
 Drugs affecting biosynthesis of nucleic acid
 Drugs destroying DNA structure and function
 Drugs interfering with transcription and blocking RNA synthesis
 Drugs affecting protein synthesis
 Hormonal agents
3. Effect on cell proliferation kinetics
 Cell cycle nonspecific drugs( CCNS)
 Cell cycle specific drugs(CCS)
 Tumor cell phase: G0 phase / Cell cycle: G1→ S → G2 → M
4. Drugs affecting nucleic acid synthesis(antimetabolites)
（1）Methothrexate (MTX)
 Mechanism: inhibit dihydrofolate reductase(DHFR), interfering synthesis of thymidylate,
purine nucleotides
 Clinical uses: childhood acute lymphoblastic leukemia and chorioepithelioma
 Toxicity: myelosuppression / Rescue method: calcium leucovorin
（2）Fluorouracil （5-Fu）: Pyrimidine antagonists
 Mechanism: convert to 5F-dUMP and inhibit thynidylate synthase,block the synthesis of
dTMP
 Clinical uses: good effect on cancer of digestive tract, breast cancer
 Toxicity : myelosuppression and mucositis
（3）Mercaptopurine （6-MP）
 Mechanism: metabolized by HGPRT to 6-thioinsisnic acid and inhibit enzymes of purine
nucleotide interconversion
 Clinical uses: childhood acute leukemia
 Toxicity : myelosuppression and gastrointestinal symptoms
（4）Hydroxurea (Hu)
 Mechanism : Inhibit ribonucleotide reductase
 Clinical uses: chronic granulocytic leukemia
 Toxicity: bone marrow depression, nausea, vomiting
（5）Cytarabine （Ara-C ）
 Mechanism: Ara-C →Ara-CMP →→Ara-CTP, competitively inhibit DNA polymerase
 Clinical uses: acute granulocytic leukemia, mononuclear leukemia
 Toxicity: severe myelosuppression , nausea etc
5. Drugs dstroying DNA structure and function
（1）Alkylating agents
① Cyclophosphamide (CTX)
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Mechanism: CTX →aldophosphamide → phosphoramide mustard
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Clinical uses: malignant lymphoma, acute leukemia

Toxicity: cystitis, alopecia, nausea, vomiting, myelosuppression
② Thiotepa( TSPA)
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Clinical uses: breast cancer, ovarian cancer, liver cancer etc

Toxicity: myelosuppression
③ Busulfan (myleran)
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Good effect on chronic granulocytic leukemia
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Toxicity: myelosuppression
④Nitrosoureas
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Drugs : carmustine(BCNU), lomustine(CCNU)
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Highly lipid-soluble, can cross BBB / Treatment of brain tumor
（2）Antitumor antibiotics
① Bleomycin （BLM）
 Clinical uses : treatment of squamous cell carcinoma of the neck, cervix, skin,
penis ,rectum and in combination therapy for lymphomas
 Toxicity:
Severe: pulmonary fibrosis
Common: anorexia, alopecia, blistering and hyperkeratosis of palms
②Mitomycin C
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Clinical uses: adenocarcinomas of the stomach, pancreas,lung and breast
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Toxicity
Severe: myelosuppression
Common: nausea, vomiting and anorexia
（3）Cisplatin & Carboplatin
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Clinical uses: Genitourinary cancers, particular ovarian and bladder cancer
Testicular cancer / in combination with vinblastine and bleomycin

Toxicity
Acute toxicity: nausea, vomiting
Renal toxicity: hydration with saline infusion & diuretics
Myelosuppression
（4）Camptothecins
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Drugs: topotecan(TPT), irinotecan(CPT-11)
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Mechanism: interfere with the activity of topoisomerase Ⅰ
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Clinical uses: cancer of lung, stomach, colon etc

No cross resistance with other anticancer drugs

Toxicity
Common: nausea, vomiting, alopecia
Dose-limiting side effect: neutropenia, thrombocytopenia
CPT-11: diarrhea
6. Drugs interfering with transcription
（1）Drugs: Dactinomycin/ Doxorubicin /Daunorubicin
（2）Mechanism: Bind tightly to double-stranded DNA through interaction between adjacent
guanine-cytosine base pair, and inhibit all forms of DNA-dependent RNA synthesis
（3）Clinical uses: narrow-spectrum
In combination with surgery and vincristine in the adjuvant treatment of Wilm’s tumor
（4）Toxicity : evident myelosuppression
（5）Doxorubicin (ADM) & Daunorubicin
 Mechanism : Bind with high affinity to DNA through intercalation and then block the
synthesis of DNA and RNA
 Clinical uses
 ADM: one of the most important anticancer drugs , treatment of carcinoma of the breast,
endometrium, ovary, testicle, thyroid, lung and many sarcoma, acute leukemia,
Hodgkin’s disease
 Daunorubicin: acute leukemia
 Adverse reactions
 Cardiac toxicity: most severe and irreversibly
 Severe or total alopecia : at standard dosage
 Myleosuppression : short duration and rapid recovery
7. Drugs affecting protein synthesis
（1）Vinblastine（VLB）& vincristine（VCR ）
①Mechanism of action
bind specifically to the microtubular protein tubulin in dimeric form, terminate assembly of
microtubules and result in mitotic arrest at metaphase, cause dissolution of the mitotic spindle
and finally interfere with chromosome segregation
②Clinical uses
 VLB: systemic Hodgkin’s disease and other lymphoma
 VCR: acute leukemia in children ( combination with predinisone)
③Toxicity
 VLB: nausea, vomiting, alopecia, myelosuppression
 VCR: neurotoxicity , include muscle weakness, peripheral neuritis and areflexia
（2）Teniposide（VM-26）& Etoposide（VP-16）
① Mechanism
Inhibit topoisomerase Ⅱ,result in DNA damage through strand breakage
② Clinical uses
VP-16: lung and testicular cancer
VM-26: brain cancer and lymphoma
③ Toxicity
Nausea, vomiting, alopecia and myelosuppression
（3）Taxol & taxotere
① Mechanism
Enhance tubulin polymerization and promote microtubule assembly
② Clinical uses:
First choice for ovarian and advanced breast cancer
③ Toxicity
Hypersensitivity/ Peripheral neuropathy/ Neutropenia , thrombocytopenia
（4）Harringtonine & Homoharringtonine
①Mechanism : Inhibit the start stage of protein synthesis, decompose the ribosome
②Clinical use: Acute granulocytic leukemia and acute mononuclear leukemia
③Toxicity : Nausea, vomiting, leukopenia and heart toxicity
（5）L-asparaginase
①Mechanism : Depletion of serum asparagine and inhibit protein synthesis in neoplastic cells
②Clinical uses: Childhood acute leukemia
8. Hormonal agents
（1）Adrenal corticosteroids : Predisone, prednisolone, dexamethasone
Actue leukemia, lymphoma and myeloma
（2）Sex hormones
Cancer of female and male breast, cancer of prostate, cancer of the endometrium of the uterus
（3）Tamoxifen
 Competitive partial agonist-inhibitor of estrogen
 Extremely useful in the treatment of breast cancer
9. Rationale for combination of antineoplastic drugs
 Cell proliferating kinetics
 The mechanism of the drugs
 Toxicity of the combinational drugs
 Anti-cancer spectrum
 Method of administering drugs
10. Toxicity of the anticancer drugs
（1）Acute toxicity
①Common toxicity: Myleosuppression /Gastrointestinal disturbance/ Alopecia
②Specific toxicity
 Cardiac toxicity: daunorubicin
 Liver toxicity: CTX, dactinomycin
 Bladder toxicity: CTX
 Neurotoxicity: VCR
 Hypersensitivity: taxol
（2）Chronic toxicity: Infertility, teratogenesis, carcinogenesi