CANCER CHEMOTHERAPY (Lecture Outline For Medical Students) 管 忠 震

Cancer Chemotherapy (1) The role of chemotherapy in cancer treatment (2) Current status of cancer chemotherapy: How effective it is? (3) Mechanism of cancer chemotherapy: a brief review (4) Difficulties in cancer chemotherapy: How to overcome? (5) New developments

A Brief Review of Natural History of Cancer Normal somatic cell mutation Malignant change Cancer cell Proliferate (Mitosis)

Cell mitosis: DNA Synthesis Mitosis RNA S phase M phase

Cancer cell: Number Increasing Cancer in situ T Local tumor mass Local infiltration & extension Locally advanced N Lymphatic spread: LN M Hemangial (Systemic spread): Remote metastasis

Cancer Chemotherapy TNM Staging System Progression of Cancer

Cancer, Treatment of Choice Localized Cancer: Surgery Locally Advanced:

Role of Chemotherapy in Cancer Treatment (1) Metastatic Cancer: Palliative or Curative Chemotherapy (2) Adjuvant Chemotherapy: to erradicate or control micro-metastasis (3) Neo-adjuvant Chemotherapy (Induction Chemotherapy) to make Surgery of RT possible to alleviate surgical damage to eradicate micro-metastasis (4) Hematological Malignancies: Primary Treatment

In Localized or Regional Cancer Cases Micro-Metastasis May occur (Sub Clinical Metastasis)

Efficacy of Chemotherapy to Cancers

Chemotherapy Curable Cancers Childhood: ALL 70% NHL >50% Burkitt’s Lymphoma >50% Wilm’s Tumor >50% Ewing’s Sarcoma >50% Embrynal >50% Rhabdomyosarcoma

Chemo-Resistant (Insensitive) Cancers Non-Small Cell Lung Cancer G.I. Cancers Pancreatic Cancer Melanoma

Mechanism of Cancer Chemotherapy(Cytostatic Drugs) Anti-proliferation (1) Blockage DNA Synthesis Blockage purined pyramidine synthesis Inhibit DNA polymerase (2) Direct Damage to DNA Breakage of DNA chain Cross-linkage, inhibit depolarization (3) Inhibit Transduction (DNA RNA) (4) Spindle toxin Mitosis damage (5) Inhibit topoisomerase

Difficulties in Cancer Chemotherapy

(1) Non-dividing Cancer Cells (Go cells) Growth Fraction (GF) and sensitivty Insensitive Cancers: Non-small Cell Lung Cancer G-I Cancers Liver Cancer, etc Go Cells in Sensitive Cancer: Recurrence

(2) Proliferating Normal Cell: Damage Myelo Suppression: Granulocytopenia Infection Thrombocytopenia Hemorrhage RBC anemia Lymphocytopenia Immune Suppression Mucous Epith Cells Stomatitis G-I reactions Germ Cells Inferlity Foetus Teratogenic, Abortion

(3) Other Organ Toxicity Cardiac, Hepatic, Renal, etc. Pulmonary (4) Drug Resistance

Methods of Improvement: Component Transfusion Protected Environment (life Island, Lamina Air Flow Unit), Hematopoietic Growth Factore (G-CSF, GM-CSF, Stem Cell Transplants)

Precaution in Cancer Chemotherapy 肿瘤化学治疗中 值 得 注 意 的 事 项 Precaution in Cancer Chemotherapy

有机结合各种治疗手段 (Multi-Modality treatment) 2. 每一患者均有具体的治疗目标: 1. 全面评估患者的病情 有机结合各种治疗手段 (Multi-Modality treatment) 2. 每一患者均有具体的治疗目标: 根治性化疗 (Curative chemotherapy) 姑息性化疗: 延长寿命 (Palliative chemotherapy) 缓解症状 Palliative Care?

4. 尽量使用标准治疗方案: ( Standard Protocol) 3. 权衡利弊 Toxicity Benefit vs Risk Cost 4. 尽量使用标准治疗方案: ( Standard Protocol) 经Clinical Study 证实 密切观察,防止及处理不良反应 (Adverse effects)

Cancer Chemotherapy: New Advances 1. Hi Dose CT/Stem Cell Transplantation 2. New Anticancer Drugs Taxanes: TAXOL, TAXOTERE Topoisomerase I Inhibitor: CPT-10, CPT-11, TOPOTECAN Gemcitabine Oxaliplatin, Lobaplatin New Theraputic Targets e.g. Anti-angioclonal(Angiostatin, Endostatin) Monoclonal Antibody: Herceptin For Breast Cancer (Her 2 neu over expression) Gene therapy