Magdy Saber Introduction to Cancer Chemotherapy and …icedoc.org/March_2008/Magdy Saber_Introduction to Cancer Chemot… · Magdy Saber Prof. of Medical Oncology, NCI, Cairo University

ASCO Advanced Course

Introduction to Cancer Introduction to Cancer Introduction to Cancer Introduction to Cancer Chemotherapy and Chemotherapy and

PharmacologyPharmacologyPharmacologyPharmacologyByBy

Dr. Magdy SaberDr. Magdy SaberByBy

Dr. Magdy SaberDr. Magdy SaberDr. Magdy SaberDr. Magdy SaberProf. of Medical Oncology, Prof. of Medical Oncology,

NCI, Cairo University NCI, Cairo University

Dr. Magdy SaberDr. Magdy SaberProf. of Medical Oncology, Prof. of Medical Oncology,

NCI, Cairo University NCI, Cairo University

South & East MediterraneanCollege of Oncology

26 – 28 March 2008Cairo - Egypt


Learning ObjectivesLearning Objectives

Af l i hi h i i h ld b blAf l i hi h i i h ld b bl

•• Identify consideration important in dosing Identify consideration important in dosing chemotherapeutic agents in older patients with cancerchemotherapeutic agents in older patients with cancer

After completing this program the participant should be able toAfter completing this program the participant should be able to

chemotherapeutic agents in older patients with cancerchemotherapeutic agents in older patients with cancer

•• Describe chemotherapy related toxicities that are more Describe chemotherapy related toxicities that are more common and/or debilitating in older patients with cancercommon and/or debilitating in older patients with cancercommon and/or debilitating in older patients with cancercommon and/or debilitating in older patients with cancer

•• Identify precautions to be taken to ameliorate theses Identify precautions to be taken to ameliorate theses toxicitiestoxicities




Chemotherapeutic agents in older patients Chemotherapeutic agents in older patients with cancer: Special considerationwith cancer: Special consideration

Anticancer Drugs

Target Effects

Elderly Elderly

Patient with Patient with

Toxic Effects

CancerCancerOther Drugs

Physiological agePhysiological ageCoCo--morbiditiesmorbidities

Goal of TreatmentGoal of TreatmentPotential toxicitiesPotential toxicities

Drug interactionsDrug interactions




Cancer and the elderlyCancer and the elderly•• Cancer is a disease of aging Cancer is a disease of aging •• Th biTh bi 33 di l didi l di•• The big The big 3 3 ——cardiovascular disease, cardiovascular disease, cancer and strokecancer and stroke—— increase with ageincrease with age•• 4 4 out of out of 5 5 persons ≥ persons ≥ 65 65 years of age years of age h h i ditih h i ditihave one or more chronic conditionshave one or more chronic conditions•• 60 60 % of all malignant tumors occur in % of all malignant tumors occur in the age group the age group 65 65 years and olderyears and older

Shown by Audisio, SIOG Shown by Audisio, SIOG 20032003

Fitness does not mean you can all Fitness does not mean you can all do the same exercise, does it?do the same exercise, does it?

-- Vulnerable = reversible problem.Vulnerable = reversible problem.

-- Frail = non reversible problems.Frail = non reversible problems.




Adverse drug reactions more Adverse drug reactions more common in the elderlycommon in the elderly

If an elderly person is started on a new medication and If an elderly person is started on a new medication and 2 2 to to 3 3 days days later they are taken to the emergency room suspect a drug reactionlater they are taken to the emergency room suspect a drug reaction



later they are taken to the emergency room, suspect a drug reaction.later they are taken to the emergency room, suspect a drug reaction.


OrganOrgan--specific agespecific age--related related physiological changesphysiological changes

•• Kidneys Kidneys

•• LiverLiver•• Cardiovascular Cardiovascular

•• HematologicalHematological•• LungsLungs

•• GI tractGI tract

HematologicalHematological

•• Nervous systemNervous system

•• EndocrineEndocrineGI tract GI tract

•• Body compositionBody composition•• Endocrine Endocrine




Chemotherapy and The ElderlyChemotherapy and The ElderlyWhat are the true limitations?What are the true limitations?

•• Drug distribution and absorption Drug distribution and absorption

•• Drug interactionsDrug interactionsgg

•• Renal functionRenal function

•• Liver functionLiver function

•• Marrow reservesMarrow reserves

•• NeurologicalNeurological




Pharmacokinetics Pharmacokinetics -- OverviewOverview




Factors that may affect GIT absorptionFactors that may affect GIT absorption•• Decreased gastric acidDecreased gastric acid secretionsecretion•• Decreased gastric acid Decreased gastric acid secretionsecretion

•• Decreased Decreased emptying timeemptying time

•• Decreased gastrointestinal tractDecreased gastrointestinal tract motilitymotilityDecreased gastrointestinal tract Decreased gastrointestinal tract motilitymotility

•• Decreased splanchnic Decreased splanchnic blood flowblood flow

•• Decreased Decreased absorption surfaceabsorption surfacepp

•• Concomitant medication, e,g., HConcomitant medication, e,g., H22 blockers, antacids, blockers, antacids, calciumcalcium

•• Compliance Compliance




Distribution of anticancer agentsDistribution of anticancer agentsThe volume of distribution of drugs is a function of The volume of distribution of drugs is a function of body compositionbody compositionand the concentration of circulatingand the concentration of circulating plasma proteinsplasma proteins such as serumsuch as serumand the concentration of circulating and the concentration of circulating plasma proteinsplasma proteins such as serum such as serum albumin and albumin and red blood cellred blood cell concentrationconcentration

•• Fat contentFat content doubles in the elderly from doubles in the elderly from 1515% to % to 3030% f b d i ht% f b d i ht3030% of body weight.% of body weight.

•• Intracellular waterIntracellular water decreases to decreases to 3333% in the % in the average average 7575--yearyear--old compared with old compared with 4242% in the % in the average average 2525--yearyear--old.old.

•• This results in a decrease in volume of This results in a decrease in volume of distribution of more polar drugs, while that of the distribution of more polar drugs, while that of the lipid soluble drugs increases. This can lead to a lipid soluble drugs increases. This can lead to a lower peak concentration and prolonged terminal lower peak concentration and prolonged terminal half.half.

Plasma-level profile of a drug




Distribution of anticancer agentsDistribution of anticancer agents

•• PlasmaPlasma albuminalbumin concentration decreasesconcentration decreasesPlasma Plasma albumin albumin concentration decreases concentration decreases as individual ages (may decrease by as individual ages (may decrease by 1515% % to to 2020% or more, especially with chronic % or more, especially with chronic illness, malnutrition, and frailty).illness, malnutrition, and frailty).

•• There is often a reduction of There is often a reduction of red blood cellred blood cellconcentrationconcentration

•• Anemia can be particularly relevant forAnemia can be particularly relevant for•• Anemia can be particularly relevant for Anemia can be particularly relevant for treatment with anthracyclines, taxanes treatment with anthracyclines, taxanes and epipodophyllotoxins that are heavily and epipodophyllotoxins that are heavily bound to red blood cellsbound to red blood cellsbound to red blood cellsbound to red blood cells

•• OtherOther medications medications may displace protein may displace protein bound drugs bound drugs

Plasma-level profile of a drug




Hepatic MetabolismHepatic Metabolism•• Reduced liver Reduced liver sizesize

•• Reduced liver Reduced liver flowflow (at a rate of (at a rate of 00..33% to % to 11..55% per year after age % per year after age 2525))

•• Age related changes in Age related changes in PP450450 (CYP) microsomal systems (declines by (CYP) microsomal systems (declines by 3232% after the age of% after the age of 7070 years)years)3232% after the age of % after the age of 70 70 years).years).

•• Polypharmacy:Polypharmacy:oo PP450 450 inducers: sex steroids, phenobarbitalinducers: sex steroids, phenobarbital

•• Genetic variability accounts for differing levels of enzyme activity that Genetic variability accounts for differing levels of enzyme activity that may lead to clinically important pharmacodynamic differencesmay lead to clinically important pharmacodynamic differences

oo PP450 450 inhibitors: cimetidine, grapefruit juice.inhibitors: cimetidine, grapefruit juice.

may lead to clinically important pharmacodynamic differencesmay lead to clinically important pharmacodynamic differences




Chemotherapy & PChemotherapy & P450 450 metabolism metabolism

A tA t 11AA22 22CC99 22CC1919 22BB66 22DD66 33AA44AgentAgent 11AA22 22CC99 22CC1919 22BB66 22DD66 33AA44

CyclophosphamideCyclophosphamide xx xx xxDocetaxelDocetaxel xxP lit l ( +P lit l ( +22CC88))Paclitaxel ( +Paclitaxel ( +22CC88)) xx xxDoxorubicinDoxorubicin xxEtoposide(+Etoposide(+22EE11)) xx (x)(x)

iiMitoxantroneMitoxantrone xxVLB/VCRVLB/VCR xx

Median number of potential drug i t ti d t i it ti t

6 (0-17) •• Phase Phase 2 2 reactions appear reactions appear interaction and toxicity per patientNumber interacting with P450 2 (0-8)

Extermann et al. ASCO 2003

unaffected by age.unaffected by age.



Extermann et al. ASCO 2003


Dose reduction in hepatic dysfunctionDose reduction in hepatic dysfunctionDrugDrug MildMild ModerateModerate SevereSevereDrugDrug MildMild ModerateModerate SevereSevereAnthracyclinesAnthracyclinesAdriamycinAdriamycinDaunorubicinDaunorubicin

5050%%2525%%

7575%%5050%%

OmitOmitOmit Omit

Taxanes Taxanes Omit Omit Omit Omit Omit Omit Vinca alkaloidsVinca alkaloidsEpipodophyllotoxinsEpipodophyllotoxins

5050%% Omit Omit Omit Omit

Synthetic alkaloidSynthetic alkaloidMethotrexate Methotrexate 00%% 2525%% Omit Omit

CyclophosphamideCyclophosphamide 00%% 55%% Omit Omit y p py p p

55--FluorouracilFluorouracil 00%% 00%% Omit Omit

Mild: bil. Mild: bil. 11..55--33%%; SGOT: ; SGOT: 6060--180180. Moderate bil. . Moderate bil. 33..11-- 55%%; SGOT: >; SGOT: >180180. Severe: bil.> . Severe: bil.> 55%%




Excretion of DrugsExcretion of Drugs•• A decline in glomerular filtration rate (GFR) is A decline in glomerular filtration rate (GFR) is

one of the most predictable changes one of the most predictable changes associated with age (associated with age (11ml per minute for ml per minute for every year over every year over 40 40 years of age).years of age).

•• Additional effects of comorbid conditions on Additional effects of comorbid conditions on renal functionrenal function

Age and GFRAge and GFR

The relationship between serum creatinine and GFRThe relationship between serum creatinine and GFR




Formulas for calculation of CrCl from SCrFormulas for calculation of CrCl from SCr

Creatinine clearance calculationCreatinine clearance calculation




Creatinine clearance calculationCreatinine clearance calculation

•• CockcroftCockcroft--Gault and Jellife equations are less accurate in theGault and Jellife equations are less accurate in theCockcroftCockcroft Gault and Jellife equations are less accurate in the Gault and Jellife equations are less accurate in the elderly and in patients with severe renal failure or decreased elderly and in patients with severe renal failure or decreased muscle mass. muscle mass.

•• The Wright formula is more accurate than the Cockcroft/GaultThe Wright formula is more accurate than the Cockcroft/GaultThe Wright formula is more accurate than the Cockcroft/Gault The Wright formula is more accurate than the Cockcroft/Gault formula in patients with a glomerular filtration rate of >formula in patients with a glomerular filtration rate of >505011

•• The MDRD (modification of diet in renal disease) formula is more The MDRD (modification of diet in renal disease) formula is more accurate than other formulas in patients with chronic renalaccurate than other formulas in patients with chronic renalaccurate than other formulas in patients with chronic renal accurate than other formulas in patients with chronic renal disease. This formula takes into account age, sex, ethnicity, serum disease. This formula takes into account age, sex, ethnicity, serum creatinine, blood urea nitrogen, and albumincreatinine, blood urea nitrogen, and albumin22

1`Marx et al, 2004; 2`Levev et al, 1999; Lichman et al, 2007




Dose reductions in renal dysfunctions Dose reductions in renal dysfunctions based on CrCl (ml/min.)based on CrCl (ml/min.)

DrugDrug 3030--6060 1010--3030 <<1010Cisplatin Cisplatin 5050%% OmitOmit OmitOmit

Carboplatin Carboplatin 2020%% 3030%% 3030%%CyclophosphamideCyclophosphamide 00%% 00%% 5050%%BleomycinBleomycin 2525%% 2525%% 5050%%Bleomycin Bleomycin 2525%% 2525%% 5050%%Methotrexate Methotrexate 5050%% Omit Omit Omit Omit Nitrosureas Nitrosureas Omit Omit Omit Omit Omit Omit




Influence of age on toxicity of anticancer drugs Influence of age on toxicity of anticancer drugs

•• Is Toxicity in older patients = Toxicity in younger patients?Is Toxicity in older patients = Toxicity in younger patients?

•• Concerns:Concerns:Performance statusPerformance statusConcomitant diseasesConcomitant diseases

•• Most evaluations and reviews of SIOG Taskforce state that fit Most evaluations and reviews of SIOG Taskforce state that fit older patients without significant coolder patients without significant co-- morbidity and without morbidity and without p gp g yysignificant functional impairment should be treated the same as significant functional impairment should be treated the same as younger patients.younger patients.




Common Toxicities in Older Persons Common Toxicities in Older Persons

•• Haematological toxicity: MyelosuppressionHaematological toxicity: MyelosuppressionHaematological toxicity: Myelosuppression Haematological toxicity: Myelosuppression

•• Cardiac toxicities: Cardiomyopathy Cardiac toxicities: Cardiomyopathy

•• GIT toxicity: MucositisGIT toxicity: Mucositis

•• N t i itN t i it•• NeurotoxicityNeurotoxicity




Haematological toxicity/ Myelosuppression Haematological toxicity/ Myelosuppression

•• R d d h i i iR d d h i i i•• Reduced haematopoietic reserve capacity:Reduced haematopoietic reserve capacity:

•• Decreased growth factor secretionDecreased growth factor secretion

•• Decreased proliferative response to growth Decreased proliferative response to growth factorsfactorsfactors factors

Lipschitz DA. Semin Oncol. 1995; 22(suppl 1) 3-5. Vose JM. Semin Oncol. 1995; 22(suppl 1) 6-8.Repetto L et al Anticancer Res 1999; 19: 879 884



Repetto L et al. Anticancer Res. 1999; 19: 879-884


Potential solutions to a decreased Potential solutions to a decreased haematopoetic reserve haematopoetic reserve

•• Dose adjustmentDose adjustment

•• Haematopoietic growth factors:Haematopoietic growth factors:G CSFG CSFGM CSFGM CSFErythropoietinErythropoietinErythropoietinErythropoietinThrombopoietic drugsThrombopoietic drugs




Cardiotoxicity/Cardiomyopathy Cardiotoxicity/Cardiomyopathy

•• f ff f•• Risk factors for cardiotoxicityRisk factors for cardiotoxicity

Previous radiotherapy to chest wallPrevious radiotherapy to chest wallPre existing cardiac diseasePre existing cardiac disease

•• C l itC l it

Pre existing cardiac diseasePre existing cardiac diseaseAge over Age over 65 65 yearsyears

•• Culprits Culprits Anthracyclines/AnthracenedioneAnthracyclines/AnthracenedioneTrastuzumabTrastuzumab55--FlurouracilFlurouracilTaxanesTaxanes




DrugDrug AcuteAcute--subacutesubacute ChronicChronic

Cytotoxic drugsCytotoxic drugs that cause Cardiotoxicitythat cause Cardiotoxicity

DrugDrug AcuteAcute--subacutesubacute ChronicChronicArrhythmiasArrhythmias PericarditisPericarditis IschemiaIschemia CardiomyopathiesCardiomyopathies

BleomycinBleomycin +/+/-- +/+/-- ++

EndoxanEndoxan ++ ++

CytarabineCytarabine +/+/-- ++

DaunorubicinDaunorubicin ++ ++ ++ ++DoxorubicinDoxorubicin55--FU/ VCR/ VLBFU/ VCR/ VLB ++

MTXMTX +/+/--

+ = convincing association; +/+ = convincing association; +/-- = limited case reports= limited case reports




DoxorubicinDoxorubicin--related Cardiotoxicity related Cardiotoxicity

Cummulative Cummulative Probability of Heart Failure (%)Probability of Heart Failure (%)dose (mg/mdose (mg/m22))

y ( )y ( )Q weekQ week Q Q 3 3 weeksweeks

4040--5959yy >>60 60 yy 4040--5959yy >>60 60 yy250 00 44 00 66 11 55 22 44250 00..44 00..66 11..55 22..44

300 00..66 00..99 22..22 33..44

400 00..77 11..22 22..33 44..66

500 11..55 22..33 55..88 66..99

600 33..99 66..11 1414..99 2222..44

700 88..77 1313..22 3030..55 4343..55

Von Hoff DO et al. Ann Intern Med. 1979; 91:710-717




Recommendation for safely delivering Recommendation for safely delivering anthracycline to older patients anthracycline to older patients

•• C ( CC ( C ))•• Cytoprotective agents e.g dexrazoxane (ICRFCytoprotective agents e.g dexrazoxane (ICRF--187187).).•• Alternative schedulesAlternative schedules

Continuous infusionContinuous infusion

•• Use of less cardiotoxic agentsUse of less cardiotoxic agents

Weekly administrationWeekly administration

Mit tMit tMitoxantroneMitoxantroneEpirubicinEpirubicinLiposomal doxorubicinLiposomal doxorubicin

•• Monitor LVEF and clinical symptomsMonitor LVEF and clinical symptoms




Cardiotoxicity of Cardiotoxicity of 55--fluorouracil fluorouracil •• May cause vascular smooth muscle constrictionMay cause vascular smooth muscle constrictionMay cause vascular smooth muscle constrictionMay cause vascular smooth muscle constriction

•• 11..66% incidence of symptomatic cardiac toxicity% incidence of symptomatic cardiac toxicity

•• Increase in asymptomatic ST changes fromIncrease in asymptomatic ST changes from 2424% to% to 6868%%Increase in asymptomatic ST changes from Increase in asymptomatic ST changes from 2424% to % to 6868%%

•• Risk factors:Risk factors:

PrePre--existing cardiac diseaseexisting cardiac diseaseggContinuous infusionContinuous infusion

Mosseri M et al. Cancer Res . 1993;53:3028-3033Rezkall S et al J Clin Oncol 1989; 7: 509 514



Rezkall S et al. J Clin Oncol. 1989; 7: 509-514


GIT Toxicity of Chemotherapy GIT Toxicity of Chemotherapy

•• Nausea and VomitingNausea and VomitingAnticipatoryAnticipatoryAcuteAcute A ti i t A t D l d

•• MucositisMucositis

AcuteAcuteDelayedDelayed

Anticipatory Acute Delayed

16 16 -- 24 24 hhChemoChemo•• MucositisMucositis

•• DiarrheaDiarrhea




Prevention of Acute Emesis Prevention of Acute Emesis

•• Single dose of one of the following Single dose of one of the following 55--HTHT33receptor receptor antagonists: antagonists:

DolacetronDolacetron 100100mg PO/IV ormg PO/IV or 11 88mg/kg IV ormg/kg IV orDolacetron Dolacetron 100100mg PO/IV or mg PO/IV or 11..88mg/kg IV ormg/kg IV orGranisetron Granisetron 00..0101mg IV ormg IV orOndansitron Ondansitron 00..1515mg/kg IVmg/kg IV

•• Plus:Plus:Dexamethasone Dexamethasone 2020mg IV or mg IV or Methylprednisolone Methylprednisolone 40 40 to to 125125mg PO or IVmg PO or IV




Prevention of Delayed Emesis Prevention of Delayed Emesis

Dexamethasone 8 PO bid 3

Metoclopramide 30-40 mg PO bid- qid x 2-4days

+ or8mg PO bid x3-4days One of the 5-HT3 receptor antagonists:

Dolacetron 100mg PO/IV or 1.8mg/kg IV x

+ or

Dolacetron 100mg PO/IV or 1.8mg/kg IV x 2-3 daysGranisetron 2mg PO, 1mg IV or 0.01mg/kg IV x 2-3 daysOndansitron 8mg PO bid-tid, 8mg IV or 0.15mg/kg IV 2-3 days




GIT mucosal toxicity of chemotherapy GIT mucosal toxicity of chemotherapy

•• Metaanalysis of Metaanalysis of 33,,351 351 patients enrolled in patients enrolled in phase III trials of colon cancerphase III trials of colon cancer

No age related difference in the likelihood ofNo age related difference in the likelihood of

•• Review of prospective colorectal cancer data Review of prospective colorectal cancer data bb

No age related difference in the likelihood of No age related difference in the likelihood of mucositis with mucositis with 55--FUFU

base base Severe mucositis more frequent in patient Severe mucositis more frequent in patient over over 70 70 years years

Sangent D et al. Proc Am Soc Clin Oncol 2000, 19:241a abstract 933Popescu RA et al J Clin Oncol 1999;17: 2412 2418



Popescu RA et al. J Clin Oncol. 1999;17: 2412-2418


GIT mucosal toxicity of chemotherapy (cont.) GIT mucosal toxicity of chemotherapy (cont.)

•• Metastatic colon cancerMetastatic colon cancer55--FU FU 600600mg/mmg/m2 2 with LV resulted in with LV resulted in 11 11 toxic toxic deaths (deaths (1010 of them were persons aged >of them were persons aged >

•• Adjuvant breast cancer Adjuvant breast cancer

deaths (deaths (10 10 of them were persons aged > of them were persons aged > 6363years)years)

jjClassic CMF in women aged Classic CMF in women aged 65 65 years or years or above had higher grades of toxicitiesabove had higher grades of toxicities

Petrelli N et al. J Clin Oncol. 1989; 7: 1419-1426Crivellari D et al. J Clin Oncol. 2000; 18: 1412-1422



Crivellari D et al. J Clin Oncol. 2000; 18: 1412 1422


Amelioration of GI mucosal toxicityAmelioration of GI mucosal toxicity

•• Oral cryotherapy and oral rinsesOral cryotherapy and oral rinses

•• Dose and schedule selectionDose and schedule selection

•• Rapid correction of dehydration and management Rapid correction of dehydration and management of symptomsof symptoms

•• Treatment of secondary infectionTreatment of secondary infection




Neurotoxicity Neurotoxicity

Peripheral neuropathy Central toxicityPeripheral neuropathy Central toxicity

Vinca alkaloidVinca alkaloidE i d h ll t iE i d h ll t i

CytarabineCytarabine55 FUFUEpipodophyllotoxinsEpipodophyllotoxins

Synthetic alkaloidSynthetic alkaloidTaxanesTaxanesCi l iCi l i

55--FUFUNitrosureasNitrosureasDacarbazineDacarbazineFl d biFl d biCisplatin Cisplatin

oxaloplatinoxaloplatinFludarabineFludarabineIfosfamideIfosfamideinterferoninterferon




SummarySummary•• Toxicity may be more severe and/or debilitating in the older personToxicity may be more severe and/or debilitating in the older person

•• D t i i th ti tD t i i th ti t d id i ifi f t th t di t thifi f t th t di t th

MyelosuppressionMyelosuppressionGI toxicityGI toxicity

CardiotoxicityCardiotoxicityNeurotoxicityNeurotoxicity

•• Determining the patientDetermining the patient-- and regimenand regimen--specific factors that predict the specific factors that predict the risk for toxic effects of chemotherapy would be clinically relevant.risk for toxic effects of chemotherapy would be clinically relevant.

•• Will the patient die of or with cancer?Will the patient die of or with cancer?

•• Morbidity of therapy > morbidity of cancer?Morbidity of therapy > morbidity of cancer?

FrailtyFrailty CoCo--morbiditymorbidity

•• What is the patient’s reserve for tolerating treatment?What is the patient’s reserve for tolerating treatment?

•• Will dependency be increased? Will dependency be increased?




•• To screen cancer patients likely to receive chemotherapy : To screen cancer patients likely to receive chemotherapy :

SummarySummary

No major organ failure (few comorbidities).No major organ failure (few comorbidities).Good performance status (no dependency).Good performance status (no dependency).Able to follow experimental treatment ( no dementia)Able to follow experimental treatment ( no dementia)Able to follow experimental treatment ( no dementia).Able to follow experimental treatment ( no dementia).Without drug interaction ( no polypharmacy).Without drug interaction ( no polypharmacy).

•• Developing new chemotherapy regimens with similar efficacy but Developing new chemotherapy regimens with similar efficacy but less toxicity in elderly patients should be a priority for futureless toxicity in elderly patients should be a priority for futureless toxicity in elderly patients should be a priority for future less toxicity in elderly patients should be a priority for future research.research.

Neither «Neither « frailfrail », nor «», nor « too sicktoo sick » patients» patients




Thank you Thank you Thank you Thank you



Documents

Magdy Saber Introduction to Cancer Chemotherapy and …icedoc.org/March_2008/Magdy Saber_Introduction to Cancer Chemot… · Magdy Saber Prof. of Medical Oncology, NCI, Cairo University