Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Cytotoxic Agents

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Effects of chemotherapy Cytotoxic Agents Effects of chemotherapy “Selective” toxicity based on characteristics that distinguish malignant cells from normal cells Antineoplastic effects Cell death Cell growth inhibited Cell differentiation

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Cell cycle Cytotoxic Agents Cell cycle

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Alkylating agents Cytotoxic Agents Alkylating agents Nitrogen mustards (eg, cyclophosphamide, melphalan) Aziridines (eg, thiotepa) Alkyl alkone sulfonates (eg, busulfan) Nitrosoureas (eg, carmustine) Nonclassic alkylating agents (eg, procarbazine) Platinum compounds (eg, carboplatin, cisplatin)

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Alkylating agents: Mechanisms of action Cytotoxic Agents Alkylating agents: Mechanisms of action * Polyfunctional compounds * Cytotoxicity results from alkylation of guanine and interference with DNA replication/transcription to RNA * Cell-cycle phase unspecific

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Antitumor antibiotics Cytotoxic Agents Antitumor antibiotics Anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin) Anthracenedione (ie, mitoxantrone) Mitomycin C Bleomycin Dactinomycin Plicamycin

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Antitumor antibiotics Mechanisms of action Cytotoxic Agents Antitumor antibiotics : Mechanisms of action * Polyfunctional agents * Principal mechanism: direct binding to DNA, causing uncoiling/breakage of the helix and impairment of DNA and RNA synthesis * Other mechanisms Free-radical formation Chelation of important metals Inhibition of topoisomerase II

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Antimetabolites Cytotoxic Agents Antimetabolites Antifols (eg, methotrexate) Purine analogues (eg, thioguanine, pentostatin, cladribine) Pyrimidine analogues (eg, fluorouracil, cytarabine, gemcitabine)

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Antimetabolites: Mechanisms of action Cytotoxic Agents Antimetabolites: Mechanisms of action * Replacing metabolites in key DNA/RNA replication molecules, thereby impairing function * Competing with metabolites at catalytic sites of key enzymes * Competing with metabolites at regulatory sites of key enzymes

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Spindle-tubule inhibitors Cytotoxic Agents Spindle-tubule inhibitors Vinca alkaloids (eg, vincristine, vinblastine, vinorelbine) Taxanes

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Topoisomerase inhibitors Cytotoxic Agents Topoisomerase inhibitors Podophyllotoxin derivatives (eg, etoposide, teniposide) Camptothecin derivatives (eg, topotecan, irinotecan)

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Hormonal agents: Categories Cytotoxic Agents Hormonal agents: Categories Additive (eg, estrogen, progestins, androgens) Ablative (eg, ovariectomy, orchiectomy) Competitive (eg, antiestrogens, antiprogestins, antiandrogens) Inhibitive (eg, aromatase inhibitors, LH-RH analogues)

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Hormonal agents: Mechanisms of action Cytotoxic Agents Hormonal agents: Mechanisms of action Modulate activity of hormones on nuclear or cytoplasmic receptors and subsequent induction of mRNA synthesis/protein synthesis/changes in cell functioning.

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Hormonal agents: Examples Cytotoxic Agents Hormonal agents: Examples Megestrol acetate for advanced breast and endometrial cancers Tamoxifen for breast cancer and in combination for other cancers, such as melanoma LH-RH agonists in combination with flutamide for androgen blockade in prostate cancer Prednisone as part of combination therapy for Hodgkin lymphoma, non- Hodgkin lymphoma, myeloma, and acute lymphoblastic leukemia; and as palliative therapy for breast and prostate cancer

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Biologic agents Other agents Biologic agents Cytokines (eg, interleukin-2, interferon alpha, colony stimulating factors) Immunomodulating reagents (eg, bacillus Calmette-Guérin, levamisole) Somatostatin analogs (eg, octreotide, lanreotide)

Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Granulocyte-colony stimulating factor (G-CSF): Mechanism of action Other agents Granulocyte-colony stimulating factor (G-CSF): Mechanism of action Produced physiologically by mononuclear phagocytes, endothelial cells, fibroblasts, neutrophils Acts to control number of circulating blood neutrophils Improves neutropenia and reduces rate of infection in patients with solid tumors receiving myelosuppressive therapy