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Chemotherapy of cancer
Dr. S. Parasuraman
Faculty of Pharmacy,
AIMST.
Anticancer drugs
• The anticancer drug either kill cancer cells or modify
their growth.
• Cancer treatment:
– Chemotherapy
– Radiotherapy
– Immunotherapy
– Surgery
Cellular
Pathways to
Malignancy
Aim of the cancer therapy
– Cure or prolong remission
– Palliation
– Adjuvant chemotherapy
• Cure or prolong remission
• Primary treatment modality for
Acute leukemias (in children) Choriocarcinoma
Wilm’s tumour (in children) Hodgkin’s disease
Ewing’s sarcoma (in children) Lymphosarcoma
Retinoblastoma (in children) Burkitt’s lymphoma
Rhabdomyosarcoma (in children) Testicular teratomas, Seminoma
Aim of the cancer therapy
• Palliation
– Life prolong by chemotherapy: Breast cancer, Ovarian
carcinoma, myeloma, prostatic carcinoma, chronic
lymphatic leukemia, chronic myeloid leukemas, non-
Hodgkin lymphomas, head and neck cancer and lung
(small cells) cancer
– Life prolong by chemotherapy: Colorectal carcinoma,
carcinoma pancreas, carcinoma stomach, carcinoma
esophagus, renal carcinoma, malignant melanomas,
bronchogenic carcinoma (non small cells), hepatoma and
sarcoma.
Aim of the cancer therapy
• Adjuvant chemotherapy:
– Drugs used to clear residual malignant cells
(micrometastases) after surgery / radiotherapy. Adjuvant
chemotherapy may achieve apparent cure (especially in
early breast, lung and colonic cancer)
Therapeutic effect of anticancer agent
• Cancer arise form a single malignant cell, the therapeutic goal
of cancer chemotherapy may require “total tumour cell kill”
• Achievement of a therapeutic effect by combination therapy.
• Therapeutic effect achieved by killing actively “growing
tumour cells”.
• Anticancer agents should act only at “specific stages in the cell
cycle” (the S phase and M phase).
Classification of anticancer agents
• Major class of drugs
A. Cytotoxic drugs
B. Targeted drugs
C. Hormonal drugs
Classification of anticancer agents
Cytotoxic drugs
1. Alkylating agents
2. Platinum coordination: Cisplatin, Carboplatin, Oxaliplatin
3. Antimetabolites
4. Microtubule damaging agents: Vincristine, Vinblastine,
Vinorelbine, Paclitaxel, Docetaxel
5. Topoisomerase-2 inhibitor: Etoposide
6. Topoisomerase-1 inhibitor: Topotecan, Irinotecan
7. Antibiotics: Actinomycin D, Doxorubicin, Daunorubicin,
Epirubicin, Bleomycins, Mitomycin C.
8. Miscellaneous: Hydroxyurea, L-Asparaginase, Tretinoin,
Arsenic trioxide
Alkylating agents
Nitrogen mustards Mechlorethamine
Cyclophosphamide
Ifosfamide
Chlorambucil
Melphalan
Ethylenimine Thio-TEPA
Alkyl sulfonate Busulfan
Nitrosoureas Carmustine
Lomustine
Triazine Dacarbazine
Temozolomide
Methylhyderazine Procarbazine
Alkylating agents
Nitrogen mustards Mechlorethamine
Cyclophosphamide
Ifosfamide
Chlorambucil
Melphalan
Ethylenimine Thio-TEPA
Alkyl sulfonate Busulfan
Nitrosoureas Carmustine
Lomustine
Triazine Dacarbazine
Temozolomide
Methylhyderazine Procarbazine
Classification of anticancer agents
Targeted drugs
1. Tyrosine proteinkinase inhibitors: Imatinib, Nilotinib
2. EGF receptor inhibitor: Gefitinib, Erlotinib
3. Angiogenesis inhibitors: Bevacizumab
4. Proteasome inhibitor: Bortezomib
5. Unarmed monoclonal antibody: Rituximab, Trastuzumab
Classification of anticancer agents
Hormonal drugs
1. Glucocorticods: Prednisolone
2. Estrogens: Fosfestrol, ethinylestradiol
3. Selective estrogen receptor modulators: Tamoxifen
4. Selective estrogen receptor down-regulators: Fulvestrant
5. Aromatase inhibitors: Letrozole, Anastrozole
6. Antiandrogen: Flutamide
7. 5-α reductase inhibitor: Finasteride
8. GnRH analogues: Nafarelin, Triotorelin
9. Progestins: Hydroxyprogesterone acetate
General Principles in chemotherapy of
cancer
• Single clonogenic malignant cell is capable of producing progeny
that kill the host. To effective cure, all malignant cells must be
killed.
• The proliferation rate of cancer cell is differ from normal cell.
The cytotoxic drugs kill cancer cell by first order kinetics.
• ‘Combined modality approach’ can be used for cancer therapy.
• Poly pharmacy can be used for achieve ‘total tumour cell kill’.
General Principles in chemotherapy of
cancer
• Cytotoxic drugs are either cell cycle nonspecific (CCNS)
or cell cycle specific (CCS)
– cell cycle nonspecific kill resting as well as dividing
cells. E.g.: Mustine, cyclophoshamide, chlorambucil,
carmustine, cisplatin, L-asparginase.
General Principles in chemotherapy of
cancer
– cell cycle specific kill only actively dividing cells.
• G1: Vinblastine
• S: Mtx, cytarabine, fludarabine, G-TG, 6-MP, 5-FU, hydroxyurea,
mitomycin C, doxorubicin, daunorubicin
• G2: Daunorubicin, bleomycin, etoposide, topotecan
• M: Vincristine, vinblastine, vinorelbine, paclitaxel, docetaxel
General toxicity of cytotoxic
drugs
• Cytotoxic drugs have more profound effect on rapidly
multiplying cells, because its targeting action in nucleic acid
and there precursors.
• Bone marrow: Depression of bone marrow results in
granulocytopenia, agranulocytosis, thrombocytopenia,
aplastic anaemia.
• Lymphoreticular tissue: Lymphocytopenia and inhibition of
lymphocyte function results in suppression of cell mediated as
well as humoral immunity.
• Oral cavity: Stomatitis, neutropenia, thrombocytopenia
• GIT: Diarrhoea, shedding of mucosa, haemorrhages, Nausea
and vomiting
• Skin: Alopecia (due to damage of cells in hair follicles)
• Gonads: Oligozoospermia in males; amenorrhoea in females.
• Foetus: Cytotoxic agents causes abortion, foetal death,
teratogenesis in pregnant women.
• Carcinogenicity: Secondary cancers, especially leukaemias,
lymphomas and histocytic tumours appear with greater
frequency many years after the use of cytotoxic drugs.
• Hyperuricaemia
• Individual drugs may produce specific adverse effects,
e.g. neuropathy by vincristine,
Cardiomyopathy by doxorubicin,
cystitis and alopecia by cyclophosphamide.
Thank you

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Introduction to chemotherapy of cancer

  • 1. Chemotherapy of cancer Dr. S. Parasuraman Faculty of Pharmacy, AIMST.
  • 2. Anticancer drugs • The anticancer drug either kill cancer cells or modify their growth. • Cancer treatment: – Chemotherapy – Radiotherapy – Immunotherapy – Surgery
  • 4. Aim of the cancer therapy – Cure or prolong remission – Palliation – Adjuvant chemotherapy • Cure or prolong remission • Primary treatment modality for Acute leukemias (in children) Choriocarcinoma Wilm’s tumour (in children) Hodgkin’s disease Ewing’s sarcoma (in children) Lymphosarcoma Retinoblastoma (in children) Burkitt’s lymphoma Rhabdomyosarcoma (in children) Testicular teratomas, Seminoma
  • 5. Aim of the cancer therapy • Palliation – Life prolong by chemotherapy: Breast cancer, Ovarian carcinoma, myeloma, prostatic carcinoma, chronic lymphatic leukemia, chronic myeloid leukemas, non- Hodgkin lymphomas, head and neck cancer and lung (small cells) cancer – Life prolong by chemotherapy: Colorectal carcinoma, carcinoma pancreas, carcinoma stomach, carcinoma esophagus, renal carcinoma, malignant melanomas, bronchogenic carcinoma (non small cells), hepatoma and sarcoma.
  • 6. Aim of the cancer therapy • Adjuvant chemotherapy: – Drugs used to clear residual malignant cells (micrometastases) after surgery / radiotherapy. Adjuvant chemotherapy may achieve apparent cure (especially in early breast, lung and colonic cancer)
  • 7. Therapeutic effect of anticancer agent • Cancer arise form a single malignant cell, the therapeutic goal of cancer chemotherapy may require “total tumour cell kill” • Achievement of a therapeutic effect by combination therapy. • Therapeutic effect achieved by killing actively “growing tumour cells”. • Anticancer agents should act only at “specific stages in the cell cycle” (the S phase and M phase).
  • 8. Classification of anticancer agents • Major class of drugs A. Cytotoxic drugs B. Targeted drugs C. Hormonal drugs
  • 9. Classification of anticancer agents Cytotoxic drugs 1. Alkylating agents 2. Platinum coordination: Cisplatin, Carboplatin, Oxaliplatin 3. Antimetabolites 4. Microtubule damaging agents: Vincristine, Vinblastine, Vinorelbine, Paclitaxel, Docetaxel 5. Topoisomerase-2 inhibitor: Etoposide 6. Topoisomerase-1 inhibitor: Topotecan, Irinotecan 7. Antibiotics: Actinomycin D, Doxorubicin, Daunorubicin, Epirubicin, Bleomycins, Mitomycin C. 8. Miscellaneous: Hydroxyurea, L-Asparaginase, Tretinoin, Arsenic trioxide
  • 10. Alkylating agents Nitrogen mustards Mechlorethamine Cyclophosphamide Ifosfamide Chlorambucil Melphalan Ethylenimine Thio-TEPA Alkyl sulfonate Busulfan Nitrosoureas Carmustine Lomustine Triazine Dacarbazine Temozolomide Methylhyderazine Procarbazine
  • 11. Alkylating agents Nitrogen mustards Mechlorethamine Cyclophosphamide Ifosfamide Chlorambucil Melphalan Ethylenimine Thio-TEPA Alkyl sulfonate Busulfan Nitrosoureas Carmustine Lomustine Triazine Dacarbazine Temozolomide Methylhyderazine Procarbazine
  • 12. Classification of anticancer agents Targeted drugs 1. Tyrosine proteinkinase inhibitors: Imatinib, Nilotinib 2. EGF receptor inhibitor: Gefitinib, Erlotinib 3. Angiogenesis inhibitors: Bevacizumab 4. Proteasome inhibitor: Bortezomib 5. Unarmed monoclonal antibody: Rituximab, Trastuzumab
  • 13. Classification of anticancer agents Hormonal drugs 1. Glucocorticods: Prednisolone 2. Estrogens: Fosfestrol, ethinylestradiol 3. Selective estrogen receptor modulators: Tamoxifen 4. Selective estrogen receptor down-regulators: Fulvestrant 5. Aromatase inhibitors: Letrozole, Anastrozole 6. Antiandrogen: Flutamide 7. 5-α reductase inhibitor: Finasteride 8. GnRH analogues: Nafarelin, Triotorelin 9. Progestins: Hydroxyprogesterone acetate
  • 14. General Principles in chemotherapy of cancer • Single clonogenic malignant cell is capable of producing progeny that kill the host. To effective cure, all malignant cells must be killed. • The proliferation rate of cancer cell is differ from normal cell. The cytotoxic drugs kill cancer cell by first order kinetics. • ‘Combined modality approach’ can be used for cancer therapy. • Poly pharmacy can be used for achieve ‘total tumour cell kill’.
  • 15. General Principles in chemotherapy of cancer • Cytotoxic drugs are either cell cycle nonspecific (CCNS) or cell cycle specific (CCS) – cell cycle nonspecific kill resting as well as dividing cells. E.g.: Mustine, cyclophoshamide, chlorambucil, carmustine, cisplatin, L-asparginase.
  • 16. General Principles in chemotherapy of cancer – cell cycle specific kill only actively dividing cells. • G1: Vinblastine • S: Mtx, cytarabine, fludarabine, G-TG, 6-MP, 5-FU, hydroxyurea, mitomycin C, doxorubicin, daunorubicin • G2: Daunorubicin, bleomycin, etoposide, topotecan • M: Vincristine, vinblastine, vinorelbine, paclitaxel, docetaxel
  • 17. General toxicity of cytotoxic drugs
  • 18. • Cytotoxic drugs have more profound effect on rapidly multiplying cells, because its targeting action in nucleic acid and there precursors. • Bone marrow: Depression of bone marrow results in granulocytopenia, agranulocytosis, thrombocytopenia, aplastic anaemia. • Lymphoreticular tissue: Lymphocytopenia and inhibition of lymphocyte function results in suppression of cell mediated as well as humoral immunity. • Oral cavity: Stomatitis, neutropenia, thrombocytopenia • GIT: Diarrhoea, shedding of mucosa, haemorrhages, Nausea and vomiting • Skin: Alopecia (due to damage of cells in hair follicles) • Gonads: Oligozoospermia in males; amenorrhoea in females.
  • 19. • Foetus: Cytotoxic agents causes abortion, foetal death, teratogenesis in pregnant women. • Carcinogenicity: Secondary cancers, especially leukaemias, lymphomas and histocytic tumours appear with greater frequency many years after the use of cytotoxic drugs. • Hyperuricaemia • Individual drugs may produce specific adverse effects, e.g. neuropathy by vincristine, Cardiomyopathy by doxorubicin, cystitis and alopecia by cyclophosphamide.