COMMON TOXICITY CRITERIA (CTC)

1 CTC Version Date: April 30, 1999 Cancer Therapy Evaluation Program1 Revised March 23, 1998 COMMON TOXICITY CRITERIA , Version , NCI, NIH, DHHS March 1998 COMMON TOXICITY CRITERIA (CTC)GradeAdverse Event01234 ALLERGY/IMMUNOLOGYA llergic reaction/hypersensitivity(including drug fever)nonetransient rash, drugfever <38 C (< F)urticaria, drug fever 38 C ( F),and/or asymptomaticbronchospasmsymptomaticbronc hospasm,requiring parenteralmedication(s), with orwithout urticaria;allergy-relatededema/angioedem aanaphylaxisNote: Isolated urticaria, in the absence of other manifestations of an allergic or hypersensitivity reaction, is graded in the DERMATOLOGY/SKIN rhinitis(including sneezing, nasalstuffiness, postnasal drip)nonemild, not requiringtreatmentmoderate, requiringtreatment--Autoimmune reactionnoneserologic or otherevidence ofautoimmune reactionbut patient isasymptomatic ( ,vitiligo), all organfunction is normal andno treatment is requiredevidence ofautoimmune reactioninvolving a non-essential organ orfunction ( ,hypothyroidism)

2 ,requiring treatmentother thanimmunosuppressivedrugsreversible autoimmunereaction involvingfunction of a majororgan or other adverseevent ( , transientcolitis or anemia),requiring short-termimmunosuppressivetreatmentauto immune reactioncausing major grade 4organ dysfunction;progressive andirreversible reaction;long-termadministration of high-dose immuno-suppressive therapyrequiredAlso consider Hypothyroidism, Colitis, Hemoglobin, sicknessnone--present-Urticaria is graded in the DERMATOLOGY/SKIN category if it occurs as an isolated symptom. If it occurs with other manifestations of allergic orhypersensitivity reaction, grade as Allergic reaction/hypersensitivity , not requiringtreatmentsymptomatic, requiringmedicationrequiring steroidsischemic changes orrequiring amputationAllergy/Immunology - Other(Specify, _____)

3 Nonemildmoderateseverelife-threatening ordisablingAUDITORY/HEARINGC onductive hearing loss is graded as Middle ear/hearing in the AUDITORY/HEARING is graded in the PAIN auditory canalnormalexternal otitis witherythema or drydesquamationexternal otitis withmoist desquamationexternal otitis withdischarge, mastoiditisnecrosis of the canalsoft tissue or boneNote: Changes associated with radiation to external ear (pinnae) are graded under Radiation dermatitis in the DERMATOLOGY/SKIN Version Date: April 30, 1999 Cancer Therapy Evaluation Program2 Revised March 23, 1998 COMMON TOXICITY CRITERIA , Version , NCI, NIH, DHHS March 1998 GradeAdverse Event01234 Inner ear/hearingnormalhearing loss onaudiometry onlytinnitus or hearing loss,not requiring hearingaid or treatmenttinnitus or hearing loss,correctable with hearingaid or treatmentsevere unilateral orbilateral hearing loss(deafness), notcorrectableMiddle ear/hearingnormalserous otitis withoutsubjective decrease inhearingserous otitis or infectionrequiring medicalintervention; subjectivedecrease in hearing.

4 Rupture of tympanicmembrane withdischargeotitis with discharge,mastoiditis orconductive hearing lossnecrosis of the canalsoft tissue or boneAuditory/Hearing - Other(Specify, _____)normalmildmoderateseverelife-threa tening ordisablingBLOOD/BONE MARROWBone marrow cellularitynormal for agemildly hypocellular or 25% reduction fromnormal cellularity foragemoderately hypocellularor >25 - 50%reduction from normalcellularity for age or >2but <4 weeks torecovery of normalbone marrow cellularityseverely hypocellular or>50 - 75% reductionin cellularity for age or4 - 6 weeks to recoveryof normal bone marrowcellularityaplasia or >6 weeks torecovery of normalbone marrow cellularityNormal ranges.

5 Children ( 18 years)90% cellularityaverageyounger adults (19-59)60 - 70%cellularity averageolder adults ( 60 years)50% cellularityaverageNote: Grade Bone marrow cellularity only for changes related to treatment not countWNL<LLN - 500/mm3200 - <500/mm350 - <200/mm3<50/mm3 Haptoglobinnormaldecreased-absent-Hemogl obin (Hgb)WNL<LLN - g/dL<LLN - 100 g/L<LLN - - < g/dL80 - <100 - < - < g/dL65 - <80 - < mmol/L< g/dL<65 g/L< mmol/LFor leukemia studies or bonemarrow infiltrative/myelophthisic processes, ifspecified in the - <25% decreasefrom pretreatment25 - <50% decreasefrom pretreatment50 - <75% decreasefrom pretreatment 75% decrease frompretreatmentHemolysis ( , immunehemolytic anemia, drug-related hemolysis , other)noneonly laboratoryevidence of hemolysis [ , direct antiglobulintest (DAT, Coombs )]

6 Schistocytes]evidence of red celldestruction and 2gmdecrease in hemoglobin,no transfusionrequiring transfusionand/or medicalintervention ( ,steroids)catastrophicconsequences ofhemolysis ( , renalfailure, hypotension,bronchospasm,emergencysplene ctomy)Also consider Haptoglobin, Version Date: April 30, 1999 Cancer Therapy Evaluation Program3 Revised March 23, 1998 COMMON TOXICITY CRITERIA , Version , NCI, NIH, DHHS March 1998 GradeAdverse Event01234 Leukocytes (total WBC)WNL<LLN - x 109 /L<LLN - 3000/mm3 - < x 109 /L 2000 - <3000/mm3 - < x 109 /L 1000 - <2000/mm3< x 109 /L<1000/mm3 For BMT studies, ifspecified in the - < X 109/L 2000 - <3000/mm3 - < x 109 /L 1000 - <2000/mm3 - < x 109 /L 500 - <1000/mm3< x 109 /L<500/mm3 For pediatric BMT studies(using age, race and sexnormal values), if specifiedin the protocol.

7 75 - <100% LLN 50 - <75% LLN 25 - 50% LLN<25% LLNL ymphopeniaWNL<LLN - x 109 /L<LLN - 1000/mm3 - < x 109 /L 500 - <1000/mm3< x 109 /L<500/mm3-For pediatric BMT studies(using age, race and sexnormal values), if specifiedin the protocol. 75 - <100%LLN 50 - <75%LLN 25 - <50%LLN<25%LLNN eutrophils/granulocytes(ANC/AGC)WNL - < x 109 /L 1500 - <2000/mm3 - < x 109 /L 1000 - <1500/mm3 - < x 109 /L 500 - <1000/mm3< x 109 /L<500/mm3 For BMT studies, ifspecified in the - < x 109 /L 1000 - <1500/mm3 - < x 109 /L 500 - <1000/mm3 - < x 109 /L 100 - <500/mm3< x 109 /L<100/mm3 For leukemia studies or bonemarrow infiltrative/myelophthisic process, ifspecified in the - <25% decreasefrom baseline25 - <50% decreasefrom baseline50 - <75% decreasefrom baseline 75% decrease frombaselinePlateletsWNL<LLN - x 109 /L<LLN - 75,000/mm3 - < x 109 /L 50,000 - <75.

8 000/mm3 - < x 109 /L 10,000 - <50,000/mm3< x 109 /L<10,000/mm3 For BMT studies, ifspecified in the - < x 109 /L 50,000 - <75,000/mm3 - < x 109 /L 20,000 - <50,000/mm3 - < x 109 /L 10,000 - <20,000/mm3< x 109 /L<10,000/mm3 For leukemia studies or bonemarrow infiltrative/myelophthisic process, ifspecified in the - <25% decreasefrom baseline25 - <50% decreasefrom baseline50 - <75% decreasefrom baseline 75% decrease frombaselineTransfusion: Plateletsnone--yesplatelet transfusions andother measures requiredto improve plateletincrement; platelettransfusionrefractoriness associatedwith life-threateningbleeding.

9 ( , HLA orcross matched platelettransfusions)For BMT studies, ifspecified in the platelet transfusion in24 hours2 platelet transfusions in24 hours 3 platelet transfusionsin 24 hoursplatelet transfusions andother measures requiredto improve plateletincrement; platelettransfusionrefractoriness associatedwith life-threateningbleeding. ( , HLA orcross matched platelettransfusions)Also consider Version Date: April 30, 1999 Cancer Therapy Evaluation Program4 Revised March 23, 1998 COMMON TOXICITY CRITERIA , Version , NCI, NIH, DHHS March 1998 GradeAdverse Event01234 Transfusion: pRBCsnone--yes-For BMT studies, ifspecified in the 2 u pRBC in 24 hourselective or planned3 u pRBC in 24 hourselective or planned 4 u pRBC in 24 hourshemorrhage orhemolysis associatedwith life-threateninganemia.

10 Medicalintervention required toimprove hemoglobinFor pediatric BMT studies, ifspecified in the 15mL/kg in 24 hourselective or planned>15 - 30mL/kg in 24hours elective orplanned>30mL/kg in 24 hourshemorrhage orhemolysis associatedwith life-threateninganemia; medicalintervention required toimprove hemoglobinAlso consider Marrow - Other(Specify, _____)nonemildmoderateseverelife-threate ning ordisablingCARDIOVASCULAR (ARRHYTHMIA)Conduction abnormality/Atrioventricular heart blocknoneasymptomatic, notrequiring treatment( , Mobitz type Isecond-degree AVblock, Wenckebach)symptomatic, but notrequiring treatmentsymptomatic andrequiring treatment( , Mobitz type IIsecond-degree AVblock, third-degree AVblock)life-threatening ( ,arrhythmia associatedwith CHF, hypotension,syncope, shock)