Narrated Chemo (100-102)

Chapter 100: 

Chapter 100 Basic Principles of Cancer Chemotherapy

Cancers: 

Cancers Most common cancers Solid tumors of the breast, lung, prostate, colon, and rectum Low growth fraction and respond poorly to drugs Rarer cancers Lymphocytic leukemia, Hodgkin ’ s disease, certain testicular cancers High growth fraction and respond well to drugs

Basic Principles of Cancer Chemotherapy: 

Basic Principles of Cancer Chemotherapy Cancer – unregulated cellular proliferation Treatment modalities Surgery Radiation Drug therapy Treatment of choice for disseminated cancers (leukemia, disseminated lymphomas, wide-spread metastases)

Basic Principles of Cancer Chemotherapy: 

Basic Principles of Cancer Chemotherapy Drug classes Cytotoxic agents Hormones and hormone antagonists Biologic response modifiers Targeted drugs

Characteristics of Neoplastic Cells: 

Characteristics of Neoplastic Cells Persistent proliferation Invasive growth Formation of metastases Immortality Etiology of cancer

The Growth Fraction and Its Relationship to Chemotherapy: 

The Growth Fraction and Its Relationship to Chemotherapy The cell cycle Four major phases The growth fraction Impact of tissue growth fraction on responsiveness to chemotherapy

PowerPoint Presentation: 

Fig. 100-1. The cell cycle.

Tissue Growth and Chemotherapy: 

Tissue Growth and Chemotherapy Chemotherapy drugs are more toxic to tissue with high growth fraction Bone marrow Skin Hair follicles Sperm Gastrointestinal tract

Obstacles to Successful Chemotherapy: 

Obstacles to Successful Chemotherapy Toxicity to normal cells Cure requires 100% cell kill Kinetics of drug-induced cell kill Host defenses contribute little to cell kill When should treatment stop?

PowerPoint Presentation: 

Fig. 100-2. Gompertzian tumor growth curve showing the relationship between tumor size and clinical status.

Obstacles to Successful Chemotherapy: 

Obstacles to Successful Chemotherapy Absence of truly early detection Solid tumors respond poorly Drug resistance Heterogeneity of tumor cells Limited drug access to tumor cells

Strategies for Achieving Maximum Benefits from Chemotherapy: 

Strategies for Achieving Maximum Benefits from Chemotherapy Intermittent chemotherapy Combination chemotherapy Benefits of drug combinations Suppression of drug resistance Increased cancer cell kill Reduced injury to normal cells Optimizing dosing schedules

PowerPoint Presentation: 

Fig. 100-3. Recovery of critical normal cells during intermittent chemotherapy. Cancer cells and normal cells (eg, cells of the bone marrow) are killed each time drugs are given. In the interval between doses, both types of cells proliferate. Because, in this example, normal cells repopulate faster than the cancer cells, normal cells are able to recover entirely between doses, whereas regrowth of the cancer cells is only partial. As a result, with each succeeding round of treatment, the total number of cancer cells becomes smaller, whereas the number of normal cells remains within a tolerable range. Note that differential loss of malignant cells is possible only if these cells repopulate more slowly than the normal cells. If cancer cells grow back as fast as normal cells do, intermittent chemotherapy will fail.

Strategies for Achieving Maximum Benefits from Chemotherapy: 

Strategies for Achieving Maximum Benefits from Chemotherapy Regional drug delivery Intra-arterial Intrathecal Other specialized routes

Major Toxicities of Cancer Chemotherapy: 

Major Toxicities of Cancer Chemotherapy Bone marrow suppression Neutropenia Thrombocytopenia Anemia Digestive tract injury stomatitis Nausea, vomiting, diarrhea

Major Toxicities of Cancer Chemotherapy: 

Major Toxicities of Cancer Chemotherapy Alopecia Hyperuricemia Reproductive toxicity Local injury from extravasation of vesicants Unique toxicities Carcinogenesis

Making the Decision to Treat: 

Making the Decision to Treat Benefits of treatment must outweigh the risks Patient must be given some idea of the benefits of proposed therapy One of these three should be possible: Cure, prolongation of life, palliation

Chapter 101: 

Chapter 101 Anticancer Drugs I: Cytotoxic Agents

Cytotoxic Anticancer Drugs: 

Cytotoxic Anticancer Drugs Largest class of anticancer drugs Act directly on cancer cells and healthy cells to cause their death About 50% of cytotoxic anticancer drugs are phase-specific Subdivided into nine major groups

Cell-Phase Specificity: 

Cell-Phase Specificity Sequence of events that a cell goes through from one mitotic division to the next Cell-cycle phase–specific drugs Toxic only to cells that are in a particular phase Must be in the in the blood continuously over a long time Cell-cycle phase–nonspecific drugs Can act during any phase of the cell cycle

Toxicity: 

Toxicity Many anticancer drugs are toxic to normal tissues – especially tissue with high growth fraction Bone marrow Hair follicles GI epithelium Germinal epithelium

Dosage, Handling, and Administration: 

Dosage, Handling, and Administration Antineoplastic drugs are often mutagenic, teratogenic, and carcinogenic Direct contact can result in local injury Extravasation of vesicants Carmustine, dacarbazine, dactinomycin, daunorubicin, doxorubicin, mechlorethamine, mitomycin, plicamycin, streptozocin, vinblastine, vincristine

Antitumor Antibiotics: 

Antitumor Antibiotics Cytotoxic drugs originally isolated from cultures of Streptomyces Used only to treat cancer – not infections Injure cells through direct interaction with DNA Poor GI absorption – IV administration Two main groups Anthracyclines and nonanthracyclines

Chapter 102: 

Chapter 102 Anticancer Drugs II: Hormonal Agents, Biologic Response Modifiers, and Targeted Drugs

Hormonal Agents: 

Hormonal Agents Used primarily for breast cancer and prostate cancer Mimic or block the actions of endogenous hormones See Table 102-1

Biologic Response Modifiers: 

Biologic Response Modifiers Enhance immune attack against cancer cells

Targeted Drugs: 

Targeted Drugs Bind with specific molecular targets on cancer cells to suppress tumor growth and promote cell death

Glucocorticoids: 

Glucocorticoids High doses required for cancer patients Used in combination with other agents to treat lymphoid tissue cancers (directly toxic) Acute and chronic lymphocytic leukemia, Hodgkin ’ s disease, non-Hodgkin ’ s lymphomas, and multiple myeloma Multiple serious side effects with high doses

Glucocorticoids: 

Glucocorticoids Also used to manage complications of cancer and cancer therapy Suppression of chemo-induced nausea and vomiting Reduction of cerebral edema Reduction of pain Suppression of hypercalcemia in steroid-responsive tumors Can improve appetite and promote weight gain

Prostate Cancer: 

Prostate Cancer Most common cause of cancer among men in United States Standard treatment of advanced prostate cancer Androgen deprivation Slows disease progression and increases comfort Lower testosterone production Block testosterone receptors with drugs

Breast Cancer: 

Breast Cancer Most common cancer affecting women in the United States Principal treatments Surgery, radiation, cytotoxic drugs, and hormonal drugs

Drugs for Breast Cancer: 

Drugs for Breast Cancer Tamoxifen (Nolvadex) Toremifene (Fareston) Raloxifene (Evista) Fulvestrant (Faslodex) Anastrozole (Arimidex) Letrozole (Femara) Exemestane (Aromasin) Trastuzumab (Herceptin)

Tamoxifen: 

Tamoxifen Used for established disease and for decreasing occurrence in high-risk patients Adjuvant therapy after surgery Treatment of metastatic disease Blocks and activates receptors in certain tissues

Tamoxifen: 

Tamoxifen Adverse effects Hot flushes Fluid retention Vaginal discharge Nausea and vomiting Menstrual irregularities

Biologic Response Modifiers: Immunostimulants: 

Biologic Response Modifiers: Immunostimulants Drugs that alter the host responses to cancer Interferon alfa-2a and interferon alfa-2b Aldesleukin (interleukin-2) (Proleukin) BCG vaccine (TheraCys, TICE BCG, Pacis)

Targeted Drugs: 

Targeted Drugs Designed to bind with specific molecules that drive tumor growth Many are antibodies that bind with specific antigens on tumor cells See Table 102-4

Angiogenesis Inhibitors: 

Angiogenesis Inhibitors Suppress formation of new blood vessels Deprive solid tumors of blood supply needed for growth Bevacizumab (Avastin) Only one approved for treating cancer Thalidomide (Thalomid) See Box 102-1