Antineoplastic Drugs


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Description of neoplasm & anti neoplastic drugs.

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Antineoplastic Drugs

  1. 2. A =Anticancer drugs cause N =Nausea and vomiting T =Treatment regimen must be followed I =Individualized dosage N =New drugs appear on the market E =Exposure time kept to a minimum O =Only a physician can administer P =Protect yourself L =Look, listen, and learn A =Assessment of laboratory tests S =Safe dosage based on weight T =Toxicities I =Inform patients C =Classification of agents
  2. 3. <ul><li>Neoplasm   </li></ul><ul><li>It is an abnormal mass of tissue as a result of  Neoplasia ( Neoplasia ( new growth  in Greek) is the abnormal proliferation of cells) Classification of Neoplasm </li></ul><ul><li>Benign </li></ul><ul><li>Potentially malignant </li></ul><ul><li>Malignant </li></ul>
  3. 4. Warning Signs of Neoplasm C hanges in bowel or bladder habits A sore that will not heal U nusual bleeding, discharge T hickening or lump in breast or elsewhere I ndigestion, difficulty swallowing O bvious change in wart or mole N agging cough, hoarseness
  4. 5. <ul><li>Antineoplastic Agent </li></ul><ul><li>Don’t kill tumor cells directly; interrupt development, growth, spread of abnormal cells </li></ul><ul><li>Normal Healthy cells </li></ul><ul><li>Interfere with cell replication </li></ul><ul><li>Antimetabolites interfere with DNA synthesis </li></ul>
  5. 6. Classification
  6. 7. According to Drug Acting Directly on Cells <ul><li>Alkalyting agent </li></ul><ul><li>Nitrogen Mustard </li></ul><ul><li>e.g. : Mechlorethamine (Mustine HCL), Cyclophosphamide, Ifosfamide. </li></ul><ul><li>Ethylenimine </li></ul><ul><li>e.g. : Thio- TEPA </li></ul><ul><li>Alkyl Sulphonate </li></ul><ul><li>e.g. : Busulfan </li></ul><ul><li>Nitrosourea </li></ul><ul><li>e.g. : Carmustine, Lomustine </li></ul><ul><li>Triazine </li></ul><ul><li>e.g. : Dacarbazine </li></ul>
  7. 8. <ul><li>Antimetabolites </li></ul><ul><li>Folate Antagonist </li></ul><ul><li>e.g.: Methotrixate </li></ul><ul><li>Purine Antagonist </li></ul><ul><li>e.g.: 6-Mercaptopurine, 6-thiogunine, Azathioprine </li></ul><ul><li>Pyrimidine Antagonist </li></ul><ul><li>e.g.: 5-Fluorouracil, Cytarabine </li></ul><ul><li>Vinka Alkaloids </li></ul><ul><li>e.g.: Vincristine, Vinblastine </li></ul>
  8. 9. <ul><li>Taxanes </li></ul><ul><li>e.g.: Paclitaxel </li></ul><ul><li>Epipodophyllotoxin </li></ul><ul><li>e.g.: Etoposide </li></ul><ul><li>Antibiotics </li></ul><ul><li>e.g.: Actinomycin, Doxorubicin, Daunorubicin, Mitoxantrone, Bleomycins, Mithramycin. </li></ul><ul><li>Miscellaneous </li></ul><ul><li>e.g.: Hydroxyurea, Procarbazine, </li></ul><ul><li>L- Asparaginase, Cisplatin, Carboplatin. </li></ul>
  9. 10. <ul><li>Drug Altering Hormonal milieu </li></ul><ul><li>Glucocorticoids </li></ul><ul><li>e.g. : Prednisolone & Its Derivatives </li></ul><ul><li>Estrogen </li></ul><ul><li>e.g.: Fosfestrol, Ethinylestradiol </li></ul><ul><li>Antiestrogen </li></ul><ul><li>e.g.: Tomoxifen </li></ul><ul><li>Antiandrogen </li></ul><ul><li>e.g.: Flutamide </li></ul><ul><li>5  reductase inhibitor </li></ul><ul><li>e.g.: Finasteride </li></ul><ul><li>GnRH analogues </li></ul><ul><li>e.g.: Naferelin, Goserelin </li></ul>
  10. 11. according to mechanism of action <ul><li>Drugs affecting biosynthesis of nucleic acid </li></ul><ul><li>Drugs destroying DNA structure and function </li></ul><ul><li>Drugs interfering with transcription and blocking </li></ul><ul><li>RNA synthesis </li></ul><ul><li>Drugs affecting protein synthesis </li></ul><ul><li>Hormonal agents </li></ul>
  11. 12. Drug Affecting Nucleic Acid Synthesis Hydroxyurea Drug Destroying DNA Structure & its Function Antitumor Antibiotics Cisplatin & carboplantin Alkylating Agent Camptothecins
  12. 13. Drugs interfering with transcription Dactinomycin Doxorubicin Daunorubicin Drugs affecting protein synthesis L - Asparaginase Podophyllotoxin : Teniposide & Etoposide Taxanes : Taxol & Taxotere Vincristine & Vinblastin
  13. 14. Alkylating agents Produce Highly reactive carbonium Ion which transfer alkyl group to position 7 of guanine by the covalent bond.
  14. 15. <ul><li>Mechlorethamine: </li></ul><ul><li>Ist Nitrogen Mustard , given by IV route </li></ul><ul><li>Acute effects: nausea, vomiting & hemodynamic changes. </li></ul><ul><li>Dose: 0.1 mg/kg i.v. daily x 4 days </li></ul><ul><li>Branded Name: Mustine 10 mg dry powder in vial </li></ul><ul><li>Cyclophosphamide: </li></ul><ul><li>It is inactive & producing active metabolite. It has prominent immunosuppressant property. </li></ul><ul><li>Dose: Oral - 2-3 mg/kg/day, i.v. – every 10-15 mg/kg, i.m. – 7-10 mg/kg/day </li></ul><ul><li>Branded Name: Endoxan, Cycloxan 50 mg tab , 200, 500, 1000 mg inj. </li></ul>
  15. 16. <ul><li>Ifosfamide: </li></ul><ul><li>Congener of Cyclophosphamide. It is utilize in breast, testicular, head & neck carcinoma </li></ul><ul><li>Dose: 200 mg </li></ul><ul><li>Generic: Holoxan 1 g vial </li></ul><ul><li>Thiotepa( TSPA) </li></ul><ul><li>It is a Ethylenimine </li></ul><ul><ul><li>Clinical uses: breast cancer, ovarian cancer, liver cancer etc </li></ul></ul><ul><ul><li>Toxicity: myelosuppression </li></ul></ul><ul><ul><li>Dose: 0.3-0.4 mg/kg 1-4 week interval </li></ul></ul><ul><ul><li>Generic: Thiotepa 15 mg per vial inj </li></ul></ul><ul><li>Busulfan (myleran) </li></ul><ul><ul><li>Good effect on chronic granulocytic leukemia </li></ul></ul><ul><ul><li>Toxicity : myelosuppression </li></ul></ul>
  16. 17. <ul><li>Nitrosourea </li></ul><ul><ul><li>Drugs : Carmustine, Lomustine </li></ul></ul><ul><ul><li>Highly lipid-soluble, can cross BBB </li></ul></ul><ul><ul><li>Treatment of brain tumor </li></ul></ul><ul><ul><li>Dose: 100-130 mg orally </li></ul></ul><ul><ul><li>Branded Name: Lomustine 40, 100 mg cap. </li></ul></ul><ul><li>Methotrixate (MTX) </li></ul><ul><ul><li>Mechanism: inhibit dihydrofolate reductase(DHFR), interfering synthesis of thynidylate, Purine nucleotides </li></ul></ul><ul><ul><li>Clinical uses: childhood acute lymphoblastic leukemia and chorioepithelioma </li></ul></ul><ul><ul><li>Toxicity: myelosuppression </li></ul></ul><ul><li>Dose : 2.5-15 mg/day </li></ul><ul><li>Generic: Neotrexate 2.5 mg tab, 2 ml inj. </li></ul>
  17. 18. Antimetabolites <ul><li>Mercaptopurine & thioguanine: </li></ul><ul><li>Converted into monoribonucleotides which inhibit the </li></ul><ul><li>conversion of IMP to adenine & guanine nucleotide. </li></ul><ul><li>Uses: acute leukemia & solid tumors </li></ul><ul><li>Dose: 6- Mercaptopurine – 2.5 mg/kg/day </li></ul><ul><li>6 Thioguanine: 100-200 mg/ day </li></ul><ul><li>Toxicity : myelosuppression and gastrointestinal symptoms </li></ul><ul><li>Generic: Purinethol, Empurine – 50 mg Tab </li></ul><ul><li>Azathioprine: </li></ul><ul><li>Effects on T lymphocytes & suppress CMI </li></ul><ul><li>Use : immunosuppressant in organ transplantation & in </li></ul><ul><li>rheumatoid arthritis </li></ul><ul><li>Dose: 3-5 mg/kg/day </li></ul>
  18. 19. <ul><ul><li>Pyrimidine antagonists </li></ul></ul><ul><li>Fluorouracil ( 5-Fu ) </li></ul><ul><ul><li>Mechanism: convert to 5F-dUMP and inhibit thynidylate synthase,block the synthesis of dTMP </li></ul></ul><ul><ul><li>Clinical uses: good effect on cancer of digestive tract, breast cancer </li></ul></ul><ul><ul><li>Toxicity : myelosuppression and mucositis </li></ul></ul><ul><ul><li>Dose: 1 gm orally on alternative days. </li></ul></ul><ul><ul><li>Branded Name: Fluracil, five fluro250 mg cap, 5 ml for i.v. inj. </li></ul></ul><ul><li>Cytarabine ( Ara-C ) </li></ul><ul><ul><li>Ara-C ->Ara-CMP ->->Ara-CTP, competitively inhibit DNA polymerase. The triphosphate of Cytarabine is an inhibitor of DNA polymerase. </li></ul></ul><ul><ul><li>Clinical uses: acute granulocytic leukemia, mononuclearcyte leukemia </li></ul></ul><ul><ul><li>Toxicity: severe myelosuppression , nausea etc </li></ul></ul><ul><ul><li>Dose: 1.5-3 mg/kg i.v. BD for 5-10 days </li></ul></ul><ul><ul><li>Branded Name: Cytarabine, cytosar & cytabin 100, 500, 1000 mg inj. </li></ul></ul>
  19. 20. <ul><li>Vinka Alkaloids </li></ul><ul><li>Mechanism of action </li></ul><ul><ul><li>Bind specifically to the micro tubular 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 </li></ul></ul>
  20. 21. <ul><li>Vincristine: </li></ul><ul><li>Use: in childhood acute leukemia, Hodgkin's disease, wilm’s tumor, ewing’s sarcoma & carcinoma lung. </li></ul><ul><li>Dose: 1.5-2 mg/m 2 BSA i.v. weekly </li></ul><ul><li>Generic: Oncovin & cytocristin 1 mg/ vial inj </li></ul><ul><li>Vinblastin: </li></ul><ul><li>Use : in Hodgkin's disease & testicular carcinoma. </li></ul><ul><li>Dose: 0.1-0.15 mg/kg </li></ul><ul><li>Generic: Vinblastin 10 mg/vial inj </li></ul><ul><li>Toxicity </li></ul><ul><ul><li>VLB: nausea, vomiting, alopecia, myelosuppression </li></ul></ul><ul><ul><li>VCR: neurotoxicity , include muscle weakness, peripheral neuritis and are flexia </li></ul></ul>
  21. 22. <ul><li>Taxanes </li></ul><ul><li>Paclitaxal </li></ul><ul><li>Mechanism: Enhance tubulin polymerization and promote microtubule assembly </li></ul><ul><li>Clinical uses: First choice for ovarian and advanced breast cancer </li></ul><ul><li>Toxicity : Hypersensitivity, Peripheral neuropathy, Neutropenia , thrombocytopenia </li></ul><ul><li>Dose: 175 mg by i.v. infusion over 3 hr, repeated every 3 weeks. </li></ul><ul><li>Branded Name: Intaxel, paxtal 30 mg in 5 ml cremophor emulsion. </li></ul><ul><li>Docetaxel: </li></ul><ul><li>More potent then Paclitaxel </li></ul><ul><li>Use: breast & ovarian cancer. Also in gastric & head, neck carcinoma. </li></ul><ul><li>Dose: 100 mg i.v over 1 hr repeat at 3 weeks </li></ul><ul><li>Branded Name: Daxotel 20 mg, 80 mg inj. </li></ul>
  22. 23. Epipodophyllotoxin Etoposide: Semi synthetic derivative of podophyllotoxin. It arrest the cells in G2 phase & cause the DNA breaks by affecting the DNA topoisomerase II function . Use: testicular tumor, lung cancer, Hodgkin's disease. Dose: 50-100 mg /day oral for 5 days. Branded Name: Peltasol 100 mg in 5 ml inj.
  23. 24. <ul><li>Camptothecin Analogues </li></ul><ul><li>Topotecan & Irinotecan are two semi synthetic analogues of Camptothecin. They act similar as Etoposide but interact with different enzyme topoisomerase I . </li></ul><ul><li>Topotecan: </li></ul><ul><li>Use: In metastatic carcinoma of ovary & small cell lung cancer. </li></ul><ul><li>AE: pain abdomen, vomiting & diarrhea </li></ul><ul><li>Dose: 1.5 mg i.v. over 30 min daily for 5 days. </li></ul><ul><li>Branded Name : Topotel 2.5 mg & 4.0 mg inj </li></ul><ul><li>Irinotecan: </li></ul><ul><li>It produces the cholinergic effects because it inhibit the AChE. </li></ul><ul><li>Use : Colorectal carcinoma, cancer lung/cervix/ovary </li></ul><ul><li>AE: body ach, weakness. </li></ul><ul><li>Dose: 125 mg i.v. over 90 min weekly for 4 weeks </li></ul><ul><li>Branded Name: Irinotel 40 mg, 100 mg inj. </li></ul>
  24. 25. Antibiotics <ul><li>Dactinomycin </li></ul><ul><li>Mechanism: bind tightly to double-stranded DNA through interaction between adjacent guanine-cytosine base pair, and inhibit all forms of DNA-dependent RNA synthesis </li></ul><ul><li>Clinical uses: narrow-spectrum </li></ul><ul><ul><li>In combination with surgery and Vincristine in the adjuvant treatment of Wilm’s tumor </li></ul></ul><ul><li>Toxicity : evident myelosuppression </li></ul><ul><li>Dose: 15  g/kg i.v. daily for 5 days. </li></ul><ul><li>Branded Name: 0.5 mg/vial inj. </li></ul>
  25. 26. Doxorubicin & Daunorubicin: <ul><li>Mechanism : Bind with high affinity to DNA through intercalation and then block the synthesis of DNA and RNA </li></ul><ul><li>Clinical uses </li></ul><ul><ul><li>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 </li></ul></ul><ul><ul><li>Daunorubicin: acute leukemia </li></ul></ul><ul><ul><li>Dose: Doxorubicin 60-75 mg slow i.v. inj. every 3 weeks. </li></ul></ul><ul><ul><li>Daunorubicin: 30-60 mg daily for 3 days repeat weekly. </li></ul></ul><ul><ul><li>Branded Name: Daunocin 20 mg/vial inj </li></ul></ul><ul><ul><li>Adrimycin Doxorubicin Oncodria 10 mg, 50 mg per vial inj. </li></ul></ul><ul><ul><li>Mitoxantrone : </li></ul></ul><ul><ul><li>It is a analogue of doxorubicin </li></ul></ul><ul><ul><li>Use : chronic myelogenous leukemia, non Hodgkin’s lymphoma & carcinoma breast. </li></ul></ul><ul><ul><li>Branded Name: 20 mg / 10 ml inj. </li></ul></ul>
  26. 27. <ul><li>Bleomycin: </li></ul><ul><li>It is mixture of glycopeptides antibiotics having anti tumor activity. </li></ul><ul><li>Dose: 30 mg twice weekly i.v./i.m. </li></ul><ul><li>Branded Name: Bleocin, Oncobleo 15 mg inj. </li></ul><ul><li>Mitomycin: </li></ul><ul><li>Use: In resistant cancer of stomach, cervix, colon, rectum, bladder etc. </li></ul><ul><li>Dose: 10 mg infused i.v. in one day. </li></ul><ul><li>Branded name: Mytomycin C-2 10 mg inj. </li></ul>
  27. 28. <ul><li>Miscellaneous Cytotoxic Drugs </li></ul><ul><li>Hydroxyurea </li></ul><ul><ul><li>Inhibit ribonucleotide reductase </li></ul></ul><ul><ul><li>Clinical uses: chronic granulocytic leukemia </li></ul></ul><ul><ul><li>Toxicity: bone marrow depression, nausea, vomiting </li></ul></ul><ul><ul><li>Dose: 20-30 mg/kg daily or 80 ml i.v. inj. </li></ul></ul><ul><ul><li>Branded Name: Cytodrox 500 mg cap. </li></ul></ul><ul><ul><li>Procarbazine: </li></ul></ul><ul><ul><li>Inhibit nucleic acid synthesis & cause chromosomal damage. </li></ul></ul><ul><ul><li>Use : Oat cell carcinoma of lung. </li></ul></ul><ul><ul><li>Dose: 100-300 mg oral daily, maintenance dose 1-2 mg/kg/day </li></ul></ul><ul><ul><li>L- Asparaginase </li></ul></ul><ul><ul><li>it inhibit the synthesis of L- Asparagines to L-aspartic acid which cause the cell death. </li></ul></ul><ul><ul><li>AE: Liver damage, pancreatitis & CNS symptoms (due to protein synthesis) </li></ul></ul><ul><ul><li>Dose: 50-200 KU/kg i.v. daily for 2-4 weeks </li></ul></ul><ul><ul><li>Branded Name: Leunase 10,000 KU per vial inj. </li></ul></ul>
  28. 29. Cisplatin & Carboplatin <ul><li>Clinical uses: </li></ul><ul><ul><li>Genitourinary cancers, particular ovarian and bladder cancer </li></ul></ul><ul><ul><li>Testicular cancer: in combination with Vinblastin and Bleomycin </li></ul></ul><ul><li>Toxicity </li></ul><ul><ul><li>Acute toxicity: nausea, vomiting </li></ul></ul><ul><ul><li>Renal toxicity: hydration with saline infusion & diuretics </li></ul></ul><ul><ul><li>Myelosuppression </li></ul></ul><ul><ul><li>Dose: 50-100 mg every 3-4 weeks </li></ul></ul><ul><ul><li>Branded name : Cisplatin, cisplate, Plantinex 10 mg, 50 mg vial. </li></ul></ul><ul><ul><li>Dose : 400 mg i.v. infusion over 15-60 min. </li></ul></ul><ul><ul><li>Branded Name: Oncocarbin 150 mg inj, kemocrab 150, 450 mg/vial inj. </li></ul></ul>
  29. 30. Hormones Glucocorticoids Primarily used in childhood acute leukemia & lymphomas . Secondary effect in Breast cancer Anti Androgen Palliative effect in advanced / metastatic cases because it increase the androgen level. Antiestrogen Effective in positive estrogen receptor as well as negative breast cancer in postmenopausal women. Estrogens Use in carcinoma of male breast. 120-240 mg orally. 5  reductase inhibitor Inhibit the conversion of testosterone to dihydrotestosterone GnRH agonists Indirectly inhibit the secretion of androgen /estrogen by suppressing the FSH & LH has effect on prostate/breast Progestin Use in temporary remission in some cases of advanced & metastatic endometrial carcinoma
  30. 31. <ul><li>Side Effects </li></ul><ul><li>Toxic effects on normal cells </li></ul><ul><li>Bone marrow suppression </li></ul><ul><li>Bleeding </li></ul><ul><li>Stomatitis </li></ul><ul><li>Nausea, vomiting, diarrhea resulting in weight loss, malnutrition </li></ul><ul><li>Hair loss </li></ul><ul><li>Fetal malformations </li></ul>
  31. 32. Toxicity of the anticancer drugs <ul><li>Acute toxicity </li></ul><ul><ul><li>Common toxicity </li></ul></ul><ul><ul><ul><li>Myelosuppression </li></ul></ul></ul><ul><ul><ul><li>Gastrointestinal disturbance </li></ul></ul></ul><ul><ul><ul><li>Alopecia </li></ul></ul></ul><ul><ul><li>Specific toxicity </li></ul></ul><ul><ul><ul><li>Cardiac toxicity: Daunorubicin </li></ul></ul></ul><ul><ul><ul><li>Liver toxicity: CTX, Dactinomycin </li></ul></ul></ul><ul><ul><ul><li>Bladder toxicity: CTX </li></ul></ul></ul><ul><ul><ul><li>Neurotoxicity: VCR </li></ul></ul></ul><ul><ul><ul><li>Hypersensitivity: Taxol </li></ul></ul></ul><ul><ul><ul><li>Chronic toxicity </li></ul></ul></ul><ul><ul><ul><li>Infertility, teratogenesis, carcinogenesis </li></ul></ul></ul>
  32. 33. Three Possible Benefits of Antineoplastic <ul><li>Cure </li></ul><ul><li>Palliation—reduce or alleviate symptoms, but do not eradicate tumor </li></ul><ul><li>Prolongation of life </li></ul>
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