Melanoma, breast Tyrosinase Normal differentiation antigen >50% melanomas Anti-sense DNA oligomer treatment: blocking oncogene expression (cid:2) Short (10 \200\22350 base), synthetic, nucleotide sequence (cid:2) Complementary to speci \201c DNA or RNA sequences (cid:2) Enter all cells easily (cid:2) Speci \201c to t arget individual oncogenes (cid:2) May produce downregulation (cid:2) Can inhibit transcrip tion/translation of single gene Inhibition can be caused by triggering RNase H \200\224deg radation of target RNA \200\224interferes with processing of pre-mRNA (cid:2) (cid:2) Examples include \200\224pancreatic carcinoma (HRAS) \200\224prostate cancer cell lines (Block bcl-2 expression) (cid:2) BUT \200\224poor ef \201ciency \200\224poor speci \201city \200\224may be incre ased cell invasiveness Initial trial results encouraging in AML and lymphoma patients (cid:2) OHO-41(655-664) 11/18/02 9:39 AM Page 663 FURTHER READING 663 Genetic tagging The insertion of a foreign marker gene into cells during a tumor biopsy, and replacing the marked cells prior to treatment can provide a sensitive new indicator of minimal residual d isease after chemo- therapy. Neomycin phosphotransferase (NeoR) \200\224an enzyme that meta bolizes the aminoglycoside, G418 \200\224has been retrovirally trans- duced ex vivo into pu rged marrow from AML and neuroblastoma patients prior to re-infusion. In those individuals with relapsed disease, as few as one in 106 cells expressing the NeoR gene has been detecte d by PCR, indicating failure of the purging process. Future directions Initial clinical studies indicate that gene therapy for cancer is safe and feasible, but ha mpered by inef \201ciency of current gene transfer tech- nology. The precise role for gene therapy in the treatment of cancer may be limited to an adjuvant or palliative role rather than attempting to eliminate bulk disease. It may also serve as an ef \201cient genetic m ark- er or enhance tumor sensitivity to chemotherapy or radiotherapy. Rapid progress in this \201eld has to be tempered by appreciation of potential new toxici ties. Transfer of DNA may initiate anti-DNA anti- body responses similar to those associate d with autoimmune diseases. The use of viral vectors may be associated with insertional mut a- genesis and activation of oncogenes leading to neoplasia, antiviral immunity, and propag ation of replication-competent viruses. Further reading Crystal, R.G. (2001) Adenoviral vectors in the gene therapy of cancer. Clin Can Res 7, W 836A Suppl 5. Huber, B., Austin, E., Davis, S., Richards, B. and Good, S. (1994) Metabolism of 5- \202uorocytosine to 5- \202uorouracil in human colorectal tumor cells transduced with the cytosine deaminase gene: signi \201cant antitumour effects when only a small percentag e of tumor cells express cytosine deaminase. Proc Nat Acad Sci USA 91, 8302 \200\2236. Xu, G., McLeod, H.L. (2001) Strategies for enzyme/prodrug cancer therapy. Clin Can Res 7, 3314 \200\22324. OHO-41(655-664) 11/18/02 9:39 AM Page 664 This page intentionally left blank OHO-App(665-682) 11/18/02 9:41 AM Page 665 Part 7 Appendices 1 NCIC common toxicity criteria (CTC) grading system (May 1991, revised) 667 2 Nomogram for determination of body surface area 681 OHO-App(665-682) 11/18/02 9:41 AM Page 666 This page intentionally left blank OHO-App(665-682) 11/18/02 9:41 AM Page 667 Appendix 1: NCIC common toxicity criteria (CTC) grading system (May 1991, revised) O H 6 6 8 O A p Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) p ( 6 6 5 Allergy None Transient rash, fever <38 C, 100.4 F Urticaria, fever = 38 C, 100.4 F, mild bronchospasm Serum sickness, bronchospasm, req parenteral meds Anaphylaxis 6 8 2 ) BLOOD/BONE MARROW 1 \211 4.0 WNL 1 White blood cells (109/1) 2.0 \200\2232.9 1.0 \200\2231.9 3.0 \200\2233.9 <1.0 / 1 Platelets (109/l) 75.0 \200\223normal 50.0 \200\22374.9 25.0 \200\22349.9 <25.0 8 / Hemoglobin (g/dl) 10.0 \200\223normal 8.0 \200\2239.9 6.5 \200\2237.9 WNL \211 2.0 <6.5 0 2 Granulocytes (109/l) (i.e. neuts.+baso.+eosin) Lymphocytes (109/l) 1.0 \200\2231.4 0.5 \200\2230.9 <0.5 1.5 \200\2231.9 9 : \211 2.0 None 1.0 \200\2231.4 0.5 \200\2230.9 <0.5 1.5 \200\2231.9 4 1 Hemorrhage (clinical) (includes nosebleeds, menorrhagia, etc.) Mild, no transfusion (includes bruise/ haematoma, petachiae) Gross, 3 \200\2234 units transfusion per episode Gross, 1 \200\2232 units transfusion per episode Massive, >4 units transfusion per episode A M P a CARDIOVASCULAR g e Arterial Venous \200\223 Deep vein thrombosis not requiring anticoagulant therapy None None Transient events Deep vein thrombosis req anticoagulant therapy \200\223 Super \201cial (excludes IV site reaction \200\224code under skin Permanent event Pulmonary embolism 6 6 8 WNL = within normal limits O H O A p p ( Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) 6 6 5 Dysrhythmias Recurrent or persistent, no therapy req None Req monitoring, or hypotension, or ventricular tachycardia, or \201brillation Asymptomatic, transient, req no therapy Req trt 6 8 2 ) 1 1 / Oedema None 3+ 2+ or dependent throughout day 1+ or dependent in evening only 4+, generalized anasarca 1 8 / 0 Function None Asymptomatic, decline of resting ejection fraction by <20% of baseline value Asymptomatic, decline of Mild CHF, responsive resting ejection fraction by to therapy >20% of baseline value Severe or refractory CHF 2 9 : 4 1 Hypertension None or no change Asymptomatic, transient increase by >20 mm Hg or to >150/100 if previously WNL. No trt req Recurrent or persistent increase by >20 mm Hg or to >150/100 if previously WNL. No trt req Hypertensive crisis Req therapy A M P a g e Hypotension None or no change Changes req no therapy (incl transient orthostatic hypotension) Req therapy & hospitalization; resolves within 48 hrs of stopping agent Req \202uid replacement or other therapy but not hospitalization Req therapy & hospitalization for 48 hrs after stopping agent 6 6 9 6 6 9 O H 6 7 0 O A p Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) p ( 6 6 Ischaemia None or no change \202attening Non-speci \201c T wave Asymptomatic, ST & T wave changes suggesting ischaemia Acute myocardial Angina without evidence for infarction infarction 5 6 8 2 ) Pain (chest) Moderate None Severe Mild Life-threatening Pericardial None Asymptomatic, effusion, no intervention req Pericarditis (rub, chest pain, Symptomatic effusion, Tamponade, drainage ECG changes) 1 1 drainage req urgently req, or constrictive pericarditis req surgery / 1 8 / 0 2 9 COAGULATION : 4 \211 0.24 \227 N >2.00 \227 N >3.00 \227 N Fibrinogin 0.49 \200\2230.25 \227 N 1.51 \200\2232.00 \227 N 2.34 \200\2233.00 \227 N WNL 0.74 \200\2230.5 \227 N 1.26 \200\2231.5 \227 N 1.67 \200\2232.33 \227 N 0.99 \200\2230.75 \227 N 1.01 \200\2231.25 \227 N 1.01 \200\2231.66 \227 N 1 Prothrombin time WNL A M Partial thromboplastin time WNL P ENDOCRINE a g Yes \211 3 months Mild e Amenorrhoea \200\223 No \200\223 \200\223 6 Cushingoid Pronounced Moderate & \211 1/day Normal \200\223 \200\223 7 0 Hot- \202ushes None Frequent & interferes with normal function Mild or <1/day \200\223 O H O A p p ( Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) 6 6 5 Gynaecomastia Pronounced or painful Normal \200\223 Mild \200\223 6 8 Impotence/libido Normal Decrease in normal function Absence of function \200\223 \200\223 2 ) 1 FLU-LIKE SYMPTOMS 1 / Arthralgia (joint pain) Moderate Severe \200\223 None Mild 1 8 / Diaphoresis (sweating) Moderate Severe \200\223 None Mild 0 2 Fever in absence of infection None (including drug fever) 38.1 \200\22340.0 C 100.5 \200\223104.5 F >40.0 C >104.0 F For <24 hrs >40.0 C (104.0 F) For >24 hrs or fever accompanied by hypotension 37.1 \200\22338.0 C 98.7 \200\223100.4 F 9 : 4 1 Fever felt to be caused by drug allergyshould be coded as ALLERGY. Non-allergicdrug fever ( e.g. as from biologics) should be coded under FLU-LIKE SYMPTOMS. If fever is due to infecti on, code INFECTION only. A M Hayfever (includes sneezing, None nasal stuf \201ness, post-nasal drip) Moderate Severe \200\223 Mild P a g e 6 Lethargy (fatigue, malaise) Mild, fall of 1 level in performance status Moderate, fall of 2 levels in Severe, fall of 3 levels in performance status performance st atus None \200\223 7 1 Myalgia (muscle ache) Moderate Severe \200\223 None Mild Rigors/chills (Gr 3 incl cyanosis) Mild or brief Pronounced and/or prolonged \200\223 None Cyanosis 6 7 1 O H 6 7 2 O A p Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) p ( 6 6 GASTROINTESTINAL 5 6 Anorexia Moderate None Severe Mild \200\223 8 2 Appetite-increased Moderate None \200\223 Mild \200\223 Increase of \211 10 stools/day or grossly bloody diarrhea, or need for parenter al support ) Diarrhea None Increase of 2 \200\2233 stools/day over pre-trt Increase of 7 \200\2239 stools/day, or incontinence, malabsorption Increase of 4 \200\2236 stools/day, or nocturnal stools 1 1 / 1 8 / 0 2 Oesophagitis/dysphagia /odynophagia Dys. or odyn. not req trt, or painless ulcers on esophagoscopy Dys. or odyn. lasting >14 days despite trt Dys. or odyn. req trt None Dys. or odyn. with 10% loss of body wt. dehydration, hosp. req 9 : 4 1 Mouth dryness Moderate None Severe Mild \200\223 A Intestinal \201stula \200\223 No Req intervention \200\223 Req operation M Heartburn (includes dyspepsia) Moderate Severe \200\223 None Mild P a g e Nausea None Intake signi \201cantly decreased but can eat Able to eat reasonable intake No signi \201cant intake \200\223 6 7 2 Small bowel obstruction Intermittent, no intervention No Req intervention \200\223 Req operation O H O A p p ( Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) 6 6 5 Pain/cramping (abdominal)(includes rectal pain) Moderate None Severe Mild \200\223 6 8 2 ) Proctitis (rectal) Tenesmus or ulcerations relieved with therapy None \200\223 Mucosal necrosis with hemorrhage or other life-threatening Tenesmus or ulcerations or other symptoms not relieved 1 1 / 1 8 / 0 Stomatitis/oral None Painless, ulcers, erythema, Painful erythema, or mild soreness With therapy painful erythema, oedema, or ulcers, and cannot eat Proctitis, mucosal necrosis, and/or req parenteral or enteral support 2 oedema, or ulcers but can eat 9 : 4 1 Taste altered Moderate None Severe Mild A M Gastritis/ulcer Req vigorous medical management or non-surgical trt No Uncontrolled by medical Perforation of bleeding management; req surgery for GI ulceration Antacid P a g e Vomiting None 2 \200\2235 episodes in 24 hrs 1 episode in 24 hrs 6 \200\22310 episodes in 24 hrs >10 episodes in 24 hrs 6 or req parenteral 7 3 6 7 3 O H 6 7 4 O A p Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) p ( 6 6 GENITOURINARY Bladder changes 5 None Light, epithelial atrophy or Generalized minor telangiectasia Severe generalized telangiectasia (often with petechiae) or reduction in bladder capacity ( <15 ml) 3.1 \200\2236.0 \227 N Symptoms not relieved Severe despite therapy Necrosis, or contracted bladder (capacity <100 ml), or \201brosis/ \201stulae 6 8 telangiectasia 2 ) 1 1 / 1 >6.0 \227 N 1.5 \200\2233.0 \227 N Symptoms relieved completely with therapy <1.5 \227 N Mild symptoms req no intervention Creatinine WNL 8 / Cystitis (non-bacterial) None 0 2 (life-threatening) cystitis 9 Urinary tract infection should be coded under infection, not genitourinary. : 4 1 Dysuria None \200\223 Dysuria not req trt Dysuria req trt \200\223 A Fistula \200\223 None Yes \200\223 M Frequency None Freq of urination or Freq of urination or nocturia twice pre-trt habit nocturia < hourly Freq with urgency and \200\223 nocturia \211 hourly Gross + clots P a g Haematuria Gross, no clots Neg Haematuria resulting from thrombocytopenia should be coded under hemorrhage, not genito urinary. Micro only Req transfusion e 6 7 Urethral obstruction Unilateral, no surgery req Not complete bilateral, Complete bilateral but stents, nephrostomy obstruction tubes or sur gery req Bilateral, no surgery req None 4 O H O A p p ( Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) 6 6 5 Proteinuria No change 1 + or <0.3 g % 4 + or > 1.0 g % or > 10 g/L 2 \200\2233 + or 0.3 \200\2231.0 g % or 3 \200\22310 g/L Nephrotic syndrome 6 8 or < 3 g/L 2 ) HEPATIC 1 \211 2.5 \227 N 5.1 \200\22320.0 \227 N 2.6 \200\2235.0 \227 N >20.0 \227 N Alk Phos or 5 \200 nucleotidase Transaminase ALAT (SGPT) WNL 1 / 1 8 \211 2.5 \227 N 5.1 \200\22320.0 \227 N 2.6 \200\2235.0 \227 N > 20.0 \227 N WNL / 0 2 \211 2.5 \227 N 5.1 \200\22320.0 \227 N 2.6 \200\2235.0 \227 N > 20.0 \227 N Transaminase ASAT (SGOT) WNL 9 : 4 >3.0 \227 N Hepatic coma Bilirubin <1.5 \227 N \200\223 WNL 1.5 \200\2233.0 \227 N Precoma \200\223 1 Liver (clinical) No change \200\223 from baseline A M P a 5.1 \200\22320.0 \227 N 2.6 \200\2235.0 \227 N <2.5 \227 N > 20.0 \227 N LDH WNL g e INFECTIONS 6 7 5 Infections None Moderate, localized infect req active trt Mild, no active trt Severe, systemic infect Life-threatening sepsis, req parenteral trt, specify site specify site 6 7 5 O H 6 7 6 O A p Grade 0 Grade 1 (Mild) Grade 2 (Moderate) Grade 3 (Severe) Grade 4 (Life-threatening) p ( 6 6 Febrile neutropenia \200\223 \200\223 Present None Fever felt to be caused by drug allergyshould be coded as ALLERGY. Non-allergicdrug fe ver (e.g. as from biologics) should be coded under FLUE-LIKE SYMPTOMS. If fever is due to i nfection, code INFECTION only. \200\223 5 6 8 2 ) METABOLIC (SI UNITS) 1 >5.1 \227 N \211 3.37 \211 1.50 >27.8 or ketoacidosis 2.1 \200\2235.0 \227 N 3.13 \200\2233.37 1.5 \200\2232.0 \227 N 2.89 \200\2233.12 Amylase <1.5 \227 N 2.64 \200\2232.88 WNL 1 / Hypercalcaemia <2.64 mmol/L 1 8 / Hypocalcaemia >2.10 mmol/L 1.73 \200\2231.51 2.10 \200\2231.93 1.92 \200\2231.74 0 2 Hyperglycaemia <6.44 mmol/L 13.9 \200\22327.8 6.44 \200\2238.90 8.91 \200\22313.8 Hypoglycaemia >3.55 mmol/L 1.66 \200\2232.18 3.03 \200\2233.55 <1.66 \211 2.0 2.19 \200\2233.02 9 : Hypokalaemia No change or > 3.5 mmol/L 3.1 \200\2233.5 2.6 \200\2233.0 2.1 \200\2232.5 4 1 A \211 0.29 \211 120 Hypomagnesaemia > 0.70 mmol/L 0.37 \200\2230.30 0.70 \200\2230.58 0.57 \200\2230.38 M Hyponatraemia No change or >135 mmol/L 131 \200\223135 126 \200\223130 121 \200\223125 P a g e NEUROLOGICAL 6 7 Cerebellar None Slight inco-ordination dysdiadochokinesis Intention tremor, dysmetria, slurred speech, nystagmus Cerebellar necrosis Locomotor ataxia 6 O H O A p p ( Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) 6 6 5 Constipation Moderate None or no Mild change Severe Ileus > 96 hrs 6 8 2 ) Cortical (includes drowsiness) None Mild somnolence Severe somnolence, confusion, disorientation, hallucinations Moderate somnolence Coma, seizures, toxic psychosis 1 1 / 1 8 Dizziness (includes lightheadedness) Moderate Severe (includes fainting) None \200\223 Mild / 0 2 Extra pyramidal/involuntary movement Moderate agitation None Mild agitation (includes restlessness) Torticollis, oculogyric crisis, severe agitation \200\223 9 : 4 1 Headache Moderate or severe but transient None Mild Unrelenting & severe \200\223 A M Hearing None or no Asymptomatic, hearing change loss on audiometry only Hearing loss interfering Deafness not with function but correctable with bearing aid Tinnitus P a correctable g e 6 7 7 Insomnia Moderate None Severe Mild \200\223 Mood No change Mild anxiety or depression Moderate anxiety or Suicidal ideation Severe anxiety or depression depression 6 7 7 O H 6 7 8 O A p Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) p ( 6 6 Motor None or no Subjective weakness, no change Mild objective weakness without signi \201cant impairment of function Objective weakness with Paralysis impairment of function 5 objective \201ndings 6 8 2 ) Personality change No change Change, not disruptive to pt Disruptive to pt or family Harmful to others or self Psychosis or family 1 1 Sensory None or no Mild paresthesias, loss of Mild or moderate change Sensory loss or paresthesias that interfere with function \200\223 / 1 deep tendon re \202exes (incl. Objective sensory loss, tingling moderate paresthesias 8 / 0 2 Vision \200\223 None or no Blurred vision change Symptomatic subtotal Blindness loss of vision 9 : 4 OCULAR 1 Conjunctivitis/keratitis Erythema or chemosis not Req trt with steroids or req steroids or antibiotics None Corneal ulceration or visible opaci \201cation \200\223 A M antibiotics Dry eye Req arti \201cial tears Normal Req enucleation Mild Severe P a Glaucoma \200\223 No change \200\223 Yes \200\223 g e 6 PULMONARY 7 8 Decrease to 26 \200\22350% of Decrease to \211 25% pre-trt Carbon Monoxide diffusion capacity (DLCO) > 90% of Decrease to 76 \200\22390% of pre- treatment value Decrease to 51 \200\22375% of pre-trt of pre-trt pre-trt O H O A p p ( Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) 6 6 5 Cough Moderate None Severe Mild 6 8 Pulmonary oedema Out-pt management Req intubation None In-pt management \200\223 2 ) Pulmonary \201brosis Radiographic changes, no symptoms Changes with symptoms \200\223 \200\223 Normal 1 1 Pneumonitis (non-infectious) Normal Radiographic changes, symptoms do not req steroids Oxygen req Req assisted ventilation Steroids req / 1 8 / 0 2 SOB (dyspnoea)(includes wheezing) None or no Asymptomatic, with change abnormality in PFTs Dyspnoea at normal level of activity Dyspnoea no signi \201cant exertion Dyspnoea at rest 9 : 4 SKIN 1 Alopecia Pronounced or total head hair loss No loss Mild hair loss Total body hair loss \200\223 A M Skin changes None Hyperpigmentation Subcut \201brosis Atrophy Ulceration or necrosis P a Desquamation None Dry desquamation Moist desquamation Con \202uent moist desquamation \200\223 g e 6 Flushing-facial Moderate None Severe Mild \200\223 7 9 Local toxicity (reaction at IV site) Pain & swelling, with in \202ammation or phlebitis None Plastic surgery indicated Pain Ulceration 6 7 9 O H 6 8 0 O A p p ( 6 6 5 6 8 2 ) 1 Grade 0 Grade 2 (Moderate) Grade 3 (Severe) Grade 1 (Mild) Grade 4 (Life-threatening) 1 / 1 8 / Rash/itch (not due to allergy) (includes recall reaction) None or no Scattered macular or change Generalized symptomatic macular, papular, or vesicular eruption Exfoliative dermatitis or ulceration dermatitis Scattered macular or papular eruption or erythema with pruritus or other associated symptom s 0 papular eruption or erythema that is asymptomatic 2 9 : 4 1 A WEIGHT M \211 20.0% \211 20.0% Weight gain 10.0 \200\22319.9% <5.0% 5.0 \200\2239.9% \200\223 P Weight loss 10.0 \200\22319.9% <5.0% 5.0 \200\2239.9% \200\223 a g e 6 8 0 OHO-App(665-682) 11/18/02 9:41 AM Page 681 Appendix 2: Nomogram for determination of body surface area OHO-App(665-682) 11/18/02 9:41 AM Page 682 682 APPENDIX 2 Nomogram for determination of body surface from height and mass Height 79 78 77 76 75 74 73 72 71 70 69 68 67 66 65 64 63 62 61 60 59 58 57 56 55 54 Body surface Mass kg 150 145 140 135 130 125 120 115 110 lb 2.80 m2 2.70 330 320 310 300 290 280 270 260 250 240 230 in cm 200 195 2.60 190 2.50 185 2.40 180 2.30 175 2.20 105 170 2.10 220 100 210 95 165 2.00 1.95 1.90 1.85 1.80 1.75 1.70 1.65 1.60 200 90 160 190 85 155 180 80 170 150 75 160 145 70 150 1.55 65 140 140 1.50 1.45 60 135 53 130 1.40 52 1.35 55 120 130 51 1.30 50 50 110 1.25 125 49 105 48 1.20 100 120 45 47 1.15 95 46 1.10 115 90 45 40 1.05 85 44 110 1.00 43 80 35 42 0.95 75 105 41 0.90 70 40 m2 kg lb 65 30 0.85 cm 100 in 39 Appendix 2: Nomogram for determination of body surface area. (Reproduced with permission fr om Geigy Scienti \201c Tables (8th edn) (ed. Lentner, C.). Ciba Geigy Ltd., Switzerland, 1 981. OHO-Ind(683-698) 11/18/02 9:41 AM Page 683 Index actinomycin D 145 acute leukemia 490 analgesics 228 for bone pain 233 NMDA (N-methyl-D-aspartate) acute lymphoblastic leukemia antagonists 232 (ALL) 490 \200\2231 opioids 231 \200\2233 World Health Organization acute myeloid leukemia (AML) 491 \200\2233 adenosine analogs 153 adoptive immunotherapy 199 adrenal cancer 380 \200\2233 etiology of cancer (WHO) ladder principles 228 \200\22330 angiogenesis, in tumor growth and metastasis 35 anorexia, symptom control 238 anthracycline antibiotics 142 \200\2234 chemical carcinogenesis 54 \200\2237 hormones 61 \200\2232 ionizing radiation 58 \200\22360 viral oncogenesis 50 \200\2233 AIDS-related malignancies 560 dosing strategy 179 antibiotic chemotherapy actinomycin D 145 anthracyclines 142 \200\2234, 179 mitomycin C (MMC) 145 \200\2236 mitoxantrone 145 antibodies, monoclonal anal cancer 570 cervical cancer 570 Hodgkin \200\231s disease 570 Kaposi \200\231s sarcoma (KS) 562 \200\2234 non-Hodgkin \200\231s lymphoma (NHL) for immunotherapy 197 \200\2238 in scintigraphy 131 566 \200\2237 anti-cancer drugs, see chemotherapy antidiuretic hormone (ADH), syndrome of inappropriate s ecretion 546 primary CNS lymphoma (PCNSL) 568 alcohol, and cancer epidemiology 5, 8 (table) antiemetics 235, 236 (table) anti-folates 147 \200\22351 anti-metabolite chemotherapy adeno sine analogs 153 anti-folates 147 \200\22351 anti-purines 151, 179 \200\22380 cytosine anal ogs 152 \200\2233 hydroxyurea 153 alkylalkane sulphonates 140 alkylating agents 138 \200\22341 allergy, NCIC-CTC grading 668 (table) alpha-fetoprotein (AFP) and germ cell tumor staging 69 \200\22371 in hepatocellular carcinoma anti-microtubule agents 163 \200\2237 anti-oestrogens, for endocrine (HCC) 77 anesthetic techniques, for pain therapy 185 anti-purines 151 control 233 \200\2234 anal cancer 340 dosing strategy 179 \200\22380 adenocarcinoma 346 and AIDS 570 chemo-irradiation therapy 174 malignant melanoma 346 practi cal issues 348 squamous cell carcinoma antisense DNA oligomers, for gene therapy 662 apocrine gland cancers 487 apoptosis, and drug resistance 168 aromatase inhibitors 184 \200 \2235 ascites, palliative surgery 89 342 \200\2234 OHO-Ind(683-698) 11/18/02 9:41 AM Page 684 684 INDEX 684 ataxia-telangiectasia (AT) 59 aziridines 141 NCIC-CTC grading 668 (table) in paraneoplastic syndromes 550 blood loss assessment 613 gastrointestinal hemorrhage 617 bacillus Calmette \200\223Gu rin (BCG) palliative surgery 89 \200\22390 vaccine 191 \200\2232 gynecological hemorrhage 615 head and neck hemorrhage 616 NCIC-CTC grading 668 (table) trea tment 614 blood vessel formation basal cell carcinomas 486 of external eye 458 B-cell chronic lymphoid leukemia 494 \200\2237 benign tumors, characteristics 39 (cid:2) 2-microglobulin, as biochemical (angiogenesis), in tumor growth and metastasis 35 marker 77 Bloom \200\231s syndrome (BS) 59 body surface area nomogram 682 bone marrow suppression 584 \200\2235 bile duct tumors 366 \200\2237 biochemical abnormalities, NCIC-CTC grading 676 (table) causes 586 NCIC-CTC grading 668 (table) neutropenia, fever management biochemical crises 626, 634 hypercalcaemia 627 \200\2239 hyperglycaemia 633 hyperkalaemia 6 31 hypoglycaemia 633 hyponatraemia 630 renal tubular dysfunction 632 biochemical markers, a nd cancer 588 pancytopenia 587 red cell transfusion 590 thrombocytopenia 589 bone pain, analgesia 233 bone scintigraphy 129 bone tumors staging 67, 77 breast cancer 76 gastrointestinal tumors 72 germ cell tumors 69 \200\22371 g estational trophoblastic tumors bone metastases, surgery 92 chondrosarcoma 524 chordoma 525 Ewing \200\231s sarcoma 520 \200\2232 osteoclastoma 524 osteosarcoma 516 \200\22319 primary bone lymphoma 525 solitary plasmacytoma 525 spindle cell sarcoma 524 67 \200\2238 ovarian cancer 73 \200\2234 prostate cancer 75 bioinformatics, applications 20 biology of cancer cell cycle 21 \200\2234 cytogenetic analy sis 32 \200\2233 growth of tumors 25 \200\2236 invasion and metastasis of tumors 33 \200 \2235 brachytherapy 120 \200\2234 brain tumors brain metastases 476 \200\2238 surgery 92 primary tumors 470 \200\2234 molecular biology techniques breast cancer 15 \200\22320 biochemical markers 76 chemoprevention trials 210 diagnosis and staging 310 \200\22311 epid emiology 298 \200\2239 genetics 300 \200\2231 management oncogenes and tumor suppressor genes 27 \200\22331 role of genetics 13 \200\22314 bisphosphonates for metastatic breast cancer 321 for pain control 233 bladder cancer 398 \200\223401 early cancer 314 \200\22316 locally advanced cancer 318 metastastic cancer 320 \200\2231 no n-invasive cancer 312 chemo-irradiation therapy 174 blood cell disorders OHO-Ind(683-698) 11/18/02 9:41 AM Page 685 INDEX 685 pathology 302 \200\2233 prognostic factors 304 screening for 306 \200\2239 hormone actions 61 \200\2232 ionizing radiation cellular effects 58 radiosensitivity syndromes breathlessness, symptom control 235, 237 59 \200\22360 oncogenes and tumor Brown-S quard syndrome 576 bullous lesions of skin, in suppressor genes 27 \200\22331 paraneoplastic syndromes 552 viral 50 \200\2233 Burkitt \200\231s lymphoma 505 carcinoid tumors 358 \200\22361 cardiovascular system, NCIC-CTC and Epstein \200\223Barr virus 52 grading 668 \200\22370 (table) castration, for endocrine cancers 183 cathepsins, and tumor invasion 34 cauda equina syndrome 577 CD44 antigen, in tumor invasion CA 15-3, and breast cancer staging 76 CA 125 and metastasis 35 as biochemical marker 77 and ovarian cancer 73 \200\2234, 418 cell adhesion, in tumor invasion and metastasis 34 \200\2235 cell cycle regulation 21 \200\2234 cell-mediated immune respons e, and cachexia in paraneoplastic syndromes 556 symptom control 238 immunotherapy 199 cadherins, in tumor invasion and central nervous system metastasis 34 brain metastases 476 \200\2238 neurological paraneoplastic calcitonin, as biochemical marker 77 calcitonin-related peptide, as biochemical marker 77 c ancer-associated retinopathy (CAR), in paraneoplastic syndromes 549 syndromes 548 \200\2239 primary brain tumors 470 \200\2234 primary CNS lymphoma (PCNSL), and AIDS 568 radiation effects on 96 cancer biology, see biology of cerebellum, paraneoplastic cerebellar cancer degeneration (PCD) 548 \200\2239 cancer of unknown primary site cervical cancer 426 \200\22330 532 clinical presentation 536 \200\2237 investigation 538 pathology 534 treatment 540 \200 \2231 and AIDS 570 and human papillomavirus (HPV) 50 \200\2231 epidemiology 6 chemical carcinogen esis 54 \200\2237 chemoprevention cancer prevention, see prevention strategies chemopreventative agents 213 \200\22316 clinical trials 210 \200\22312 strategies for 208 \200\22310 cancer staging, see staging of cancer cancer therapy, psychosocial chemotherapy aspects, see psychosocial aspects of cancer alkylating agents 138 \200\22341 anti-metabolites capecitabine 150 carboplatin 154 \200\2236 adenosine analogs 153 anti-folates 147 \200\22351 anti-purines 151 cytosine analogs 152 \200\2233 hydroxyurea 153 dosing strategy 178 \200\2239 carcinoembryonic antigen (CEA), and colorectal cancer staging 72 carcinogenesis anti-microtubule agents 163 \200\2237 anti-tumor antibiotics chemical 54 \200\2237 OHO-Ind(683-698) 11/18/02 9:41 AM Page 686 686 INDEX chemotherapy (contd.) coagulopathy actinomycin D 145 anthracyclines 142 \200\2234 mitomycin C (MMC) 145 \200\2236 mitoxantrone 145 NCIC-CTC grading 670 (table) in paraneoplastic syndromes 550 colorectal cancer 324 adjuvant chemotherapy 328 \200\22330 advanced cancer, chemotherapy and bone marrow suppression 584 \200\2235 332 \200\2235 cisplatin and derivatives 154 \200\2238 combination drug therapy 136 \200\2237 combination with radiotherapy biochemical markers 72 radiotherapy 336 surgery 326 \200\2237 173 \200\2234 common toxicity criteria (CTC), National Cancer Institute (of Canada) (NCIC), see NCIC-CTC grading system dose intensi \201cation 170 \200\2232 drug development process 643 \200\2236 drug discover y chemical screening methods communication with patients, see psychosocial aspects of cancer conformal radiotherapy 96, 105, 648 constipation, symptom control 638 \200\2239 molecular target orientated approach 639 \200\22343 drug resistance 237 \200\2238 anthracycline antibiotics 142 \200\2233 anti-microtubule agents 163 \200\2239 and gene ther apy 657 constitutional symptoms, in paraneoplastic syndromes 556 counseling of patients, and palliative pharmacokinetics and care 240 \200\2233 curative surgery 87 Cushing \200\231s syndrome 546 cutaneous cancers epi demiology 7 of external eye 458 \200\2239 malignant melanoma 482 \200\2234 non-melanoma can cers 486 \200\2237 pharmacodynamics 175 \200\22380 psychosocial aspects 254 topoisomerase inhibitors 159 \200\22362 see also speci \201c canc er types 2-chlorodeoxyadenosine 153 cholangiocarcinomas 366 \200\2237 chondrosarcoma 524 chordoma 52 5 choriocarcinoma 438 \200\22340 cutaneous disorders NCIC-CTC grading 679 \200\22380 biochemical markers 67 \200\2238 (table) chromosome abnormalities, cytogenetic analysis 32 \200\2233 in paraneoplastic syndromes 552 cyclin-dependent kinases (CDKs), and cell cycle regulation 21 \200\2234 cyclins, and cell c ycle regulation 21 \200\2234 cytogenetic analysis 32 \200\2233 cytokeratin fragments, as chronic lymphoid leukaemias (CLL) 494 \200\2237 cigarette smoking and cancer epidemiology 4 \200\2235, 8 (table) biochemical marker 77 cytokines, for immunotherapy and chemical carcinogenesis 56 cisplatin 156 \200\2238 192 \200\2237 cisplatin derivatives 154 \200\2236 cytosine analogs 152 \200\2233 cytosine arabinoside (Ara-C) 152 classi \201cation of tumors 43 grading 44 histological identi \201cation 40 \200\2232 TNM staging 78 \200\2239 tumor type s 39 clinical trials daunorubicin 142 \200\2234 decision making, and chemoprevention trials 210 \200\22312 methods 222 \200\2233, 645 \200\22356 quality of life assessment 224 \200\2236 communication with patients 252 OHO-Ind(683-698) 11/18/02 9:41 AM Page 687 INDEX 687 2-deoxycoformycin (pentostatin) Eastern co-operative oncology group (ECOG), performance status scale 80 153 dependence on others, psychosocial impact 256 eccrine gland cancers 487 electrolyte disturbances dermatological paraneoplastic syndromes 552 hypercalcaemia 627 \200\2239 hyperkalaemia 631 hyponatraemia 630 NCIC-CTC grading 676 (tabl e) in paraneoplastic syndromes dermatomyositis, in paraneoplastic syndromes 549 diet and cancer epidemiology 5 \200\2236, 8 (table) 547 chemical carcinogenesis renal tubular dysfunction 632 56 electron beam therapy 106 \200\22310 electron microscopy, diagnostic uses diffuse large cell non-Hodgkin \200\231s lymphoma 506 46 2,2-di \202uorodeoxycytidine (gemcitabine) 152 \200\2233 distress, identi \201cation and emergencies in oncology acute hemorrhage 612 \200\22317 biochemical crises 626, 634 hypercalcaemia 627 \200\2239 hy perglycaemia 633 hyperkalaemia 631 hypoglycaemia 633 hyponatraemia 630 renal tubular dysfun ction intervention 251 DNA mutations 27 DNA viruses hepatitis B (HBV) virus 51 herpes viruses 52 human papillomavirus (HPV) 632 50 \200\2231 docetaxel 166 (table) bone marrow suppression 584 \200\22390 dosing strategy 179 gastrointestinal obstruction doxorubicin 142 \200\2234 620 \200\2231 dosing strategy 179 drug development process raised intracranial pressure 600 \200\2234 643 \200\2236 spinal cord compression 574 \200\22382 stridor 606 \200\2239 superior vena cava obstruction drug discovery chemical screening methods 638 \200\2239 592 \200\2237 molecular target orientated urinary tract obstruction 622 \200\2233 approach 639 \200\22343 emotional aspects of cancer, see drug resistance psychosocial aspects of cancer anthracycline antibiotics encephalomyelopathies, in 142 \200\2233 paraneoplastic syndromes 548 anti-microtubule agents endocrine cancers 163 \200\2239 adrenal cancer 380 \200\2233 etiology 61 \200\2232 neuroblastoma 384 \200\2236 scintigraphy 130 thyroid cancer 376 \200\2239 see also endocrine therapy and gene therapy 657 drugs chemical carcinogenesis from 56 \200\2237 chemotherapy, see chemotherapy ductal carcinoma of the breast, see endocrine paraneoplastic syndromes 546 \200\2237 breast cancer endocrine system abnormalities, NCIC-CTC grading 670 \200\2231 (table) dying, mode of, and palliative care 242 \200\2233 OHO-Ind(683-698) 11/18/02 9:41 AM Page 688 688 INDEX endocrine therapy eyes breast cancer 315 \200\22316, 320 clinical practice 188 endocrine gland ablation 183 enzyme inhibition 184 \200\2235 hormone agonists 183 \200\2234 hormone antagonists 185 predictive indices of response external eye cancers 458 \200\2239 intra-ocular tumors 459 \200\22360 NCIC-CTC grading 678 (table) 186 resistance to 187 see also endocrine cancers endometrial adenocarcinoma Fanconi \200\231s anemia (FA) 60 fever in bone marrow suppression 588 NCIC-CTC grading 671 (table) in paraneoplastic syndromes 556 422 \200\2234 environmental factors \201brosarcomas, uterine 424 \200\2235 FISH ( \202uorescence in situ hybrdization) 18 \200\22319 and cancer epidemiology 4, 8 (table) chemical carcinogenesis 54 \200\2237 intervention strategies \201stulas, palliative surgery 88 \200\2239 \202ow cytometry, applications 48 \202oxu ridine (2 \200\223 \202uoro-2 \200\231- deoxyuridine) 150 209 \200\22310 enzyme inhibitors, for endocrine therapy 184 \200\2235 epidemiology 8 (table) \202udarabine 153 \202u-like symptoms, NCIC-CTC alcohol 5 diet 5 \200\2236 environmental factors 4, 7 \200\2239 genetic factors 4 infection s 6 \200\2237 smoking 4 \200\2235 solar radiation 7 see also prevention strategies grading 671 (table) \202uorescence in situ hybrdization (FISH) 18 \200\22319 2- \202uoro-2 \200\231-deoxyuridine ( \202oxuridine) 150 \202uoropyrimidines 149 \200\22351 5- \202uorouracil (5-FU) 149 \200\22351 folate bioche misty, anti-folate chemotherapy 147 \200\22351 epigenetic carcinogens 54 \200\2236 epirubicin 142 \200\2234 Epstein \200\223Barr virus (EB V) 52 and cancer epidemiology 6 follicular non-Hodgkin \200\231s lymphoma 504 \200\2235 food intakes erythema, in paraneoplastic and cancer epidemiology 5 \200\2236, 8 syndromes 552 (table) erythrocyte disorders, in chemical carcinogenesis 56 fractionation, in radiotherapy paraneoplastic syndromes 550 erythrocyte transfusion, in bone marrow suppression 590 chemo-irradiation therapy 174 estra mustine phosphate 166 (table) etiology of cancer, see etiology of 98 \200\223100, 648 \200\2239 frozen section examination 45 ftorafur (tegafur) 150 cancer Ewing \200\231s sarcoma 520 \200\2232 chemo-irradiation therapy gall bladder cancer 368 \200\2239 gastric cancer 354 \200\2237 gastrin, as biochemical mark er 77 gastrointestinal cancer anal cancer 340 \200\2238 biliary tract cancer 366 \200\2239 biochemical markers 72 174 of soft tissue 528 \200\2239 external beam radiotherapy 101 \200\2235, 648 extracellular matrix, degradation, and tumor invasion 33 \200\2234 OHO-Ind(683-698) 11/18/02 9:41 AM Page 689 INDEX 689 carcinoid tumors 358 \200\22361 colorectal cancer, see colorectal germ cell tumors biochemical markers 69 \200\22371 testicular cancer 410 \200\22315 gestational trophoblasti c disease biochemical markers 67 \200\2238 choriocarcinoma 438 \200\22340 hydatidiform mole s 436 \200\2238 placental-site trophoblastic tumor (PSTT) 440 \200\2231 cancer gastric cancer 354 \200\2237 liver cancer 362 \200\2235 management controversies 374 oesophageal cancer 350 \200\2233 pancreatic cancer 370 \200\2233 small intestine tumors 35 8 \200\22361 gastrointestinal tract gliomas 470 \200\2234 glucagon, as biochemical marker abnormalities, NCIC-CTC grading 672 \200\2233 (table) 77 hemorrhage 617 glutathione, and drug resistance palliative surgery 89 \200\22390 168 obstruction 620 \200\2231 gonadotrophin-releasing hormone agonists, for medical castration 183 palliative surgery 88 radiation effects on 96 gemcitabine grading of tumors 44 granulocytes, NCIC-CTC grading (2,2-di \202uorodeoxycytidine) 152 \200\2233 668 (table) gene therapy 656 growth of tumors 25 \200\2236 gynecological cancers antisense DNA oligomers 662 drug resistance genes 657 gene delivery 201, 656 \200\2237, 658 cervical cancer 426 \200\22330 ovarian cancer 418 \200\22321 (table) biochemical markers 73 \200\2234 immunotherapy 660 \200\2231, 662 trophoblastic tumors (table) 436 \200\22341 uterine cancer 422 \200\2235 vaginal cancer 432 \200\2233 vulval cancer 433 \200\2234 gynecological hemorrhage marker gene tagging 663 pro-drug activation therapy 659, 660 (table) tumor suppressor genes 657 genetic pro-drug activation therapy 615 (GPAT) 660 (table) genetics and epidemiology 4 intervention strategies 209 and molecular biology 13 \200\22314 molecula r biology techniques hematological malignancies acute leukemia 490 \200\2233 chronic lymphoid leukaemias 15 \200\22320 genitourinary cancers (CLL) 494 \200\2237 Hodgkin \200\231s disease 498 \200\223501 myeloma 508 \200\22312 non-Ho dgkin \200\231s lymphoma (NHL) bladder and ureter cancer 398 \200\223401 prostate cancer 402 \200\2235 biochemical markers 75 screening for 406 \200\2238 502 \200\2236 and AIDS 566 \200\2237 hematological paraneoplastic renal cancer 390 \200\2233 testicular cancer 410 \200\22315 Wilms \200\231 tumor 394 \200 \2237 syndromes 550 hemoglobin, NCIC-CTC grading genitourinary disorders, NCIC-CTC 668 (table) grading 674 \200\2235 (table) genomic instability disorders, haemopoiesis, and bone marrow suppression 584 \200\2235 radiosensitivity syndromes 59 \200\22360 haemoptysis 612 OHO-Ind(683-698) 11/18/02 9:41 AM Page 690 690 INDEX hemorrhage and gestational trophoblastic assessment 613 gastrointestinal 617 tumor staging 67 \200\2238 human herpes virus 8 (HHV 8), and Kaposi \200\231s sarcoma 52 \200\2233 palliative surgery 89 \200\22390 gynecological 615 head and neck 616 NCIC-CTC grading 668 (table) treatment 614 head and nec k cancer human papillomavirus (HPV) 50 \200\2231 and cervical cancer epidemiology 6 human T-cell leukemia virus-1 (HTLV-1) 53