world cancer report - iarc

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6-MERCAPTOPURINE 6-THIOGUANINE Inhibit purine ring synthesis (6-MP) Abnormal DNA from false precursor METHOTREXATE Inhibits dihydrofolate reductase 5-FLUOROURACIL Inhibits thymidylate synthetase HYDROXYUREA Inhibits ribonucleotide reductase CYTARABINE Inhibits DNA polymerase ETOPOSIDE Inhibits topoisomerase II PURINE SYNTHESIS PYRIMIDINE SYNTHESIS RIBONUCLEOTIDES DEOXYRIBONUCLEOTIDES Fig. 6.12 Summary of the mechanisms and sites of action of selected cancer chemotherapeutic drugs. DNA RNA PROTEINS ENZYMES MICROTUBULES ALKYLATING AGENTS Cross-link DNA PROCARBAZINE Multiple mechanisms of DNA damage ANITIBIOTICS Direct binding to DNA, often by intercalation Some of these drugs also inhibit topoisomerase II L-ASPARAGINASE Deaminates L-asparagine VINCA ALKALOIDS Inhibit microtubules TAXANES Stabilize microtubules Medical oncology 283
Responsiveness Cancer (in decreasing order of efficacy) Category 1 Germ cell, leukaemias, lymphomas, choriocarcinoma Category 2 Breast, colorectal, ovarian, osteosarcoma, Ewing’s sarcomas, Wilms tumour Category 3 Lung, bladder, prostate, stomach, cervical Category 4 Head and neck Category 5 Liver, melanoma, pancreatic, brain, renal, thyroid Table 6.7 Categorization of cancer by effectiveness of chemotherapy. For many curable cancers, the initial therapy is the most important. Any dose reduction, delay or drug substitution can adversely affect response rate. Managers and patients must understand that reducing the drug dosage or number of cycles to save money is unacceptable. Adjuvant chemotherapy is now of proven value in breast and colon cancer. Again, rigid adherence to protocols is essential to maximize results. Recently several high cost drugs have been marketed for common cancers. Although capable of a significant response rate in patients with metastatic disease, 284 Cancer management such responses may be of short duration and may only prolong survival by weeks. To what extent some of these new agents should replace older and cheaper generic agents has not yet been determined in well designed trials with relevant endpoints, which include cost benefit analysis [2]. Inevitably this will have a subjective element and will vary with the overall allocation of cancer treatment resources in a country. Categories of effectiveness Protocols for drug use, and the determination of which agents should be used in the treatment of which cancers, has fre- Fig. 6.13 Combination chemotherapy is more effective than a single agent for treatment of Hodgkin disease. (ABVD = adriamycin [doxorubicin], bleomycin, vinblastine and dacarbazine; BEACOPP = bleomycin, etoposide, adriamycin [doxorubicin], cyclophosphamide, oncovin [vincristine], procarbazine and prednisone; COPP = cyclophosphamide, oncovin [vincristine], procarbazine and prednisone). quently been determined empirically. Clinical trials are developed for this purpose, and recognized standards, extending from informed patient consent through to adequate statistical analysis, have been established for such trials. Often, cytotoxic drugs are employed (usually in combination) at the maximum possible dose. Dosage is limited by toxicity: the consequence of the agent reaching, and hence affecting, normal tissue. Certain toxicity, such as hair loss, may be of limited significance but death of proliferating cells in the gut, bone marrow or other sites may provoke nausea, myelosuppression or other adverse effects. There are more than 200 types of cancer and these respond variably to chemotherapy. Tumours can be split into five categories with regard to the relative usefulness of chemotherapy (Table 6.7). This provides a basis for examining the overall health gain of defined interventions. This will of course change as new drugs with greater efficacy are introduced. Category 1: Tumours for which there is evidence that the use of a single or a combination of drugs used alone or with other therapeutic modalities will result in cure as defined by a normal life span in some and prolongation of survival in most patients. Category 2: Tumours where the average survival is prolonged when chemotherapy is used as an adjuvant to local surgery or radiotherapy in the early stages of disease. Category 3: Tumours where there is evidence that a single drug or a combination will produce clinically useful responses in more than 20% of patients. Prolongation of survival occurs in most responding patients but may be of short duration. Category 4: Tumours where local control may be improved by using chemotherapy before, during or after surgery and radiotherapy. Category 5: Tumours for which there are currently no effective drugs. Objective responses occur in less than 20% of patients and there is no evidence of survival benefit in randomized controlled trials when compared to best supportive care.
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WORLD HEALTH ORGANIZATION WHO OMS I
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WORLD CANCER REPORT Editors Bernard
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CONTENTS Foreword 9 1 The global bu
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The global burden of cancer Cancer
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Fig. 1.2 Incidence and mortality of
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Central and Southern Europe differ
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Incidence of cancer in South Centra
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from documentation of disease to a
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TOBACCO SUMMARY >In addition to lun
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Fig. 2.3 Smoking by children is inc
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Cancers positively Sex Standardized
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PHARMACOLOGICAL APPROACHES TO SMOKI
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level the dose—response relations
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lipoprotein-associated cholesterol,
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Agent Cancer site/cancer Main indus
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Industry, occupation Cancer site/ca
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to occupational exposures in develo
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Air pollutant WHO Air Quality Guide
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der cancer of the order of 50% is p
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AFLATOXIN B 1 HEPATITIS VIRUS (chro
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Fig. 2.30 Correlation between regio
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MEDICINAL DRUGS SUMMARY > Certain d
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Drug or drug combination Cancer IAR
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Agent or substance Cancer site/canc
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sources of electromagnetic fields [
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CHRONIC INFECTIONS SUMMARY > Infect
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Infection Subclinical Mutagenic fac
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TUMOURS ASSOCIATED WITH HIV/AIDS Ap
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DIET AND NUTRITION SUMMARY > Up to
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Fig. 2.54 The age-adjusted mortalit
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OVERWEIGHT, OBESITY AND PHYSICAL AC
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IMMUNOSUPPRESSION SUMMARY >Persiste
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Fig. 2.64 Cancer following immunosu
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Syndrome Gene Location Cancer site/
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viduals, confirmation of a gene def
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REPRODUCTIVE FACTORS AND HORMONES S
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PHYTO-ESTROGENS AND CANCER PEVENTIO
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Indicator Number of oral contracept
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Mechanisms of tumour development Th
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The stages in tumorigenesis have be
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PRECURSOR LESIONS IN CHEMOPREVENTIO
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CARCINOGEN ACTIVATION AND DNA REPAI
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adducts, a few weeks or months for
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I Reactive oxygen species Methylati
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which remove the mismatched bases,
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Common human oncogenes Many common
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product of the RB1 gene (pRb) and a
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ates a molecular bridge between p53
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potential cancer genes altered thro
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One of the earliest genes to be ide
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Regulation of the cell cycle and co
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CELL-CELL COMMUNICATION SUMMARY > C
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Connexin genes and tumour suppressi
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APOPTOSIS SUMMARY > The term apopto
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Caspase-8 Caspase-3 c-FLIP Procaspa
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ways. Several options are under inv
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INVASION AND METASTASIS SUMMARY > T
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laminin, entactin and also heparan
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Target Example of agent Comments Ad
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organs, and to respond to local gro
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TOBACCO CONTROL SUMMARY > Tobacco-i
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Region Deaths due to % of total dea
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ipated, is primarily attributable t
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smoke. This may be achieved in part
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there is no evidence for the effica
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industries, processes and occupatio
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stoves arises in rural areas of dev
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Climbing plants on trellis at end r
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HEPATITIS B VACCINATION SUMMARY > P
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Fig. 4.17 Chronic active HBV-associ
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HUMAN PAPILLOMAVIRUS VACCINATION SU
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Vaccine Site of trial Number of pat
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prolonged use. Similar drugs, that
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aspirin and other non-steroidal ant
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SCREENING FOR BREAST CANCER SUMMARY
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Fig. 4.35 Cumulative mortality from
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SCREENING FOR PROSTATE CANCER SUMMA
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Fig. 4.39 Poster designed for an an
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is around 10% for cancer (out of ev
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45 with one positive rehydrated FOB
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eing based on (i) time trends in th
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Fig. 4.48 Women at a clinic in Indi
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SCREENING FOR ORAL CANCER SUMMARY >
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India will provide useful informati
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cer incidence following cure of inf
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100 50 25 10 5 2.5 1 Japan Males Fe
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Human cancers by organ site Maligna
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tobacco smoking: age at start, aver
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diagnosis is usually confirmed by h
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is frequent and survival rates are
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Fig. 5.14 Physician reading digital
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Markers of prognosis in breast canc
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cer in the contralateral breast (Ch
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100 50 25 10 5 2.5 1 Japan Chile Po
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depends on staging. Small intramuco
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Fig. 5.30 A diet rich in fresh frui
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ane protein involved in cell adhesi
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LIVER CANCER SUMMARY > About 560,00
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Fig. 5.39 A woman in the Gambia pre
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REFERENCES 1. Ferlay J, Bray F, Par
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Certain Possible Uncertain Age Andr
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Management The dramatic division be
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TUMOUR NORMAL Gastrula PGC 2n Impri
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CANCERS OF THE FEMALE REPRODUCTIVE
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Fig. 5.62 Five-year relative surviv
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Inheritance of high-penetrance gene
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invasive malignant. Malignant germ
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OESOPHAGEAL CANCER SUMMARY >Cancer
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Fig. 5.76 A radiographic view of an
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with a stent; laser recannulation,
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Fig. 5.82 Risk of bladder cancer am
Page 225 and 226: Partial cystectomy is appropriate f
Page 227 and 228: poorly known since hypopharyngeal c
Page 229 and 230: Fig. 5.92 Oral leukoplakia with mil
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Page 233 and 234: T Fig. 5.101 Nuclear magnetic reson
Page 235 and 236: Fig. 5.106 Five-year relative survi
Page 237 and 238: Fig. 5.109 The immediate aftermath
Page 239 and 240: A B Fig. 5.113 Acute myeloid leukae
Page 241 and 242: Fig. 5.118 Five-year relative survi
Page 243 and 244: Fig. 5.120 Age-specific incidence a
Page 245 and 246: Hereditary condition Mode of inheri
Page 247 and 248: MELANOMA SUMMARY > Approximately 13
Page 249 and 250: Fig. 5.131 Primary melanoma with a
Page 251 and 252: THYROID CANCER SUMMARY > Cancer of
Page 253 and 254: Papillary carcinoma RET/PTC TRK BRA
Page 255 and 256: KIDNEY CANCER SUMMARY > Cancer of t
Page 257 and 258: Stage Clear cell carcinoma Papillar
Page 259 and 260: TUMOURS OF THE NERVOUS SYSTEM SUMMA
Page 261 and 262: ing the optic tract, brain stem and
Page 263 and 264: mut = mutant p53 wt = wildtype p53
Page 265 and 266: SURGICAL ONCOLOGY SUMMARY > Surgica
Page 267 and 268: Year Radical mastectomy (%) Modifie
Page 269 and 270: TELEMEDICINE The prospects for tele
Page 271 and 272: Equipment Energy 50% depth dose App
Page 273 and 274: CANCER EDUCATION IN MEDICAL COURSES
Page 275: Fig. 6.10 Crystals of cisplatin: mo
Page 279 and 280: Most of the world’s most common c
Page 281 and 282: treatment of cancer. The problems l
Page 283 and 284: duction. It is clear that tumour ce
Page 285 and 286: REHABILITATION SUMMARY > Rehabilita
Page 287 and 288: cer and its associated disability.
Page 289 and 290: REFERENCES 1. Garden FH, Gillis TA
Page 291 and 292: Cancer pain relief varies and in so
Page 293 and 294: EMERGING ISSUES IN PALLIATIVE CARE
Page 295 and 296: Cancer control The negative impact
Page 297 and 298: priority to cancer control activiti
Page 299 and 300: Prevention of cancer Every country
Page 301 and 302: - Assessing the magnitude of the ca
Page 303 and 304: high-risk women. Further details on
Page 305 and 306: ecords departments are either rudim
Page 307 and 308: THE INTERNATIONAL AGENCY FOR RESEAR
Page 309 and 310: in the capitals/urban areas of four
Page 311 and 312: in the overall cancer strategy. WHO
Page 313 and 314: 68% 1955 1975 1995 2025 32% 40% by
Page 315 and 316: Fig. 7.15 A grandfather at work in
Page 317 and 318: Fig. 7.17 Main causes of death in d
Page 319 and 320: Contributors and Reviewers Sources
Page 321 and 322: Dr Vera Luiz da Costa e Silva Tobac
Page 323 and 324: Georgia Moore Centers for Disease C
Page 325 and 326: REVIEWERS Dr Sandra E. Brooks 405 W
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2.53 T. Norat and E. Riboli, IARC 2
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Gastroenterology, 118(2 Suppl 1): S
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5.106 & 5.107 IARC/SEER/Osaka Cance
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4.17 R. Lambert, IARC/Adapted from
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Brain cancer, see nervous system tu
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Fibroblast growth factor (FGF), 117
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Microarray, 240 Micronutrients, 65,
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S Saccharin, 64, 85 Salicin, 153 Sa
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