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 〇 • 〇 〇
〇 〇 〇 〇 〇 〇 〇 〇〇 〇〇 〇
Proliferate (Mitosis)
D oubl i ng
Cell mitosis:
• DNA
• Synthesis • RNA • S phase
Mitosis M phase
Cancer cell: Number Increasing
• •T • • • •N •M • Cancer in situ Local tumor mass Local infiltration & extension Locally advanced Lymphatic spread: LN Hemangial (Systemic spread): Remote metastasis
Cancer Chemotherapy
TNM Staging System
T1 N0M0 T2 T3 N0M0 T4 TxN1M0 N2 N3 TxNxM1
Progression of Cancer
Early, localized
Localized Cancer
Infiltration & Local extension
Locallly advanced
Regional LN involvement Remote or Systemic metastasis
Reginal Metastatic
Cancer, Treatment of Choice
• Localized Cancer: Surgery • Locally Advanced:
If Surgery not possible, Radio therapy Chemotherapy Radio + Chemo (Radio-sensitizer) Chemo Radio Radio, Chemo Surgery (Neo. Adjuvant Chemotherapy) If Surgery possible, Post-operative Radio or Chemo (Adjuvant Chemotherapy) · Reginal: Radiotherapy Chemo (Adjuvant) En-bloc Surgery, if possible therapy · Metastatic Cancer: Chemotherapy (Palliative or Curative)
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)
e.g.
(1) Stage II Breast Cancer Breast Cancer with (+) Axillary L.N. (N1 or N2) Mo, Surgery Possible Actually, Micro Metastasis present LN<4, 50%(Micro-Met+) LN>4, 80%(Micro-Met+) Recurrence following Surgery Adjuvant Chemotherapy necessary
(2) Osteogenic Sarcoma of Lower ectremities Chest X-ray(-) Amputation, 80% Recurrence Rate Reason: Micro Metastasis present Treatment: Surery + Intensive Adjuvant Chemotherapy
Efficacy of Chemotherapy to Cancers
Chemotherapy Curable Cancers
• Childhood: • ALL • NHL
•
· Adult: · Chorio-Carcinoma · Testis Cancer · Hodgkins’ Disease · Aggressive NHL · AML 90% >75% 70% >50% 25%-50%
• • • •
70% >50% Burkitt’s Lymphoma >50% Wilm’s Tumor >50% Ewing’s Sarcoma >50% Embrynal >50% Rhabdomyosarcoma
· Ovarians Cancer 10%-20%
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 Thrombocytopenia RBC anemia Lymphocytopenia Infection Hemorrhage 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)
肿瘤化学治疗中 值得注意的事项
Precaution in Cancer Chemotherapy
• 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 • 缓解症状 (Palliative chemotherapy)
– Palliative Care?
• 3. 权衡利弊
– – Benefit vs – Toxicity 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