CTCAE 4 Revisions 6/14/2010 This file lists minor revisions to the base 4.0 data files released 5/29/2009. Revised data files are initially labeled with "rev1" ... at the end of their filenames, and for rev1 only Excel revised files were produced; other formats are produced if there is demand and time to do so. The rev2 version led to a consolidated set of 4.01 release files. The Archive directory stores release files prior to the current release. CTCAE Release v4.03 6/14/2010 This update includes minor edits to textural descriptions of 15 terms and definitions for 3 of those terms. Anemia Grade 3 changed to: Hgb <8.0 g/dL; <4.9 mmol/L; <80 g/L; transfusion indicated Febrile neutropenia Grade 3 changed to: ANC <1000/mm3 with a single temperature of >38.3 degrees C \ (101 degrees F) or a sustained temperature of >=38 degrees C (100.4 degrees F) for more than one hour Definition changed to: A disorder characterized by an ANC <1000/mm3 and a single temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of >=38 degrees C (100.4 degrees F) for more than one hour. Hemolysis Grade 2 changed to: Evidence of hemolysis and >=2 gm decrease in hemoglobin Hearing impaired Grade 1 changed to: Adults enrolled on a Monitoring Program (on a 1, 2, 3, 4 and 8 kHz audiogram): Threshold shift of 15 - 25 dB averaged at 2 contiguous test frequencies in at least one ear. Adults not enrolled in Monitoring Program: subjective change in hearing in the absence of documented hearing loss. Pediatric (on a 1, 2, 3, 4, 6 and 8 kHz audiogram): Threshold shift >20 dB at 8 kHz in at least one ear. Grade 2 changed to: Adults enrolled in Monitoring Program (on a 1, 2, 3, 4, 6 and 8 kHz audiogram): Threshold shift of >25 dB averaged at 2 contiguous test frequencies in at least one ear. Adults not enrolled in Monitoring Program: hearing loss but hearing aid or intervention not indicated; limiting instrumental ADL. Pediatric (on a 1, 2, 3, 4, 6 and 8 kHz audiogram): Threshold shift >20 dB at 4 kHz and above in at least one ear. Grade 3 changed to: Adults enrolled in Monitoring Program (on a 1, 2, 3, 4, 6 and 8 kHz audiogram): Threshold shift of >25 dB averaged at 3 contiguous test frequencies in at least one ear; therapeutic intervention indicated. Adults not enrolled in Monitoring Program: hearing loss with hearing aid or intervention indicated; limiting self care ADL. Pediatric (on a 1, 2, 3, 4, 6 and 8kHz audiogram): hearing loss sufficient to indicate therapeutic intervention, including hearing aids; threshold shift >20 dB at 3 kHz and above in at least one ear; additional speech-language related services indicated. Grade 4 changed to: Adults: Decrease in hearing to profound bilateral loss (absolute threshold >80 dB HL at 2 kHz and above); nonservicable hearing. Pediatric: Audiologic indication for cochlear implant and additional speech-language related services indicated. Activated partial thromboplastin time prolonged Grade 1 changed to: >ULN - 1.5 x ULN Alanine aminotransferase increased Grade 2 changed to: >3.0 - 5.0 x ULN Grade 3 changed to: >5.0 - 20.0 x ULN Aspartate aminotransferase increased Grade 2 changed to: >3.0 - 5.0 x ULN Grade 3 changed to: >5.0 - 20.0 x ULN Carbon monoxide diffusing capacity decreased Grade 1 changed to: 3 - 5 units below LLN; for follow-up, a decrease of 3 - 5 units (ml/min/mm Hg) below the baseline value Grade 2 changed to: 6 - 8 units below LLN; for follow-up, an asymptomatic decrease of >5 - 8 units (ml/min/mm Hg) below the baseline value Lymphocyte count decreased Grade 1 changed to: =7.3 Hypercalcemia Grade 1 changed to: Corrected serum calcium of >ULN - 11.5 mg/dL; >ULN - 2.9 mmol/L; Ionized calcium >ULN - 1.5 mmol/L Grade 2 changed to: Corrected serum calcium of >11.5 - 12.5 mg/dL; >2.9 - 3.1 mmol/L; Ionized calcium >1.5 - 1.6 mmol/L; symptomatic Grade 3 changed to: Corrected serum calcium of >12.5 - 13.5 mg/dL; >3.1 - 3.4 mmol/L; Ionized calcium >1.6 - 1.8 mmol/L; hospitalization indicated Grade 4 changed to: Corrected serum calcium of >13.5 mg/dL; >3.4 mmol/L; Ionized calcium >1.8 mmol/L; life-threatening consequences Definition changed to: A disorder characterized by laboratory test results that indicate an elevation in the concentration of calcium (corrected for albumin) in blood. Hyperuricemia Grade 1 changed to: >ULN - 10 mg/dL (0.59 mmol/L) without physiologic consequences Grade 3 changed to: >ULN - 10 mg/dL (0.59 mmol/L) with physiologic consequences Hypocalcemia Grade 1 changed to: Corrected serum calcium of =3.5 g/24 hrs; Pediatric: urine P/C >1.9 Alopecia Grade 1 changed to: Hair loss of <50% of normal for that individual that is not obvious from a distance but only on close inspection; a different hair style may be required to cover the hair loss but it does not require a wig or hair piece to camouflage Grade 2 changed to: Hair loss of >=50% normal for that individual that is readily apparent to others; a wig or hair piece is necessary if the patient desires to completely camouflage the hair loss; associated with psychosocial impact Release 4.02 (rev. 4) - 10/06/2009 This update corrects technical errors mostly limited to some 20 AE term definitions in the Excel file version. Two additional errors affecting two AE term definitions in all versions were corrected in the new OWL and Excel files: Left ventricular systolic dysfunction added space between words "may include" Hirsutism added period to end of definition Release 4.02 (rev. 3) - 9/15/2009 77 AE Grades had minor fixes, none affecting meaning. 4 terms had fixes to definition text Remaining changes were to case, space and punctuation. Release 4.01 (rev. 2) - 7/14/2009 1 AE term definition added, 2 fixed, extra spaces removed: Grade 2 Hypoglycemia Missing definition added. Grade 1 Chronic Kidney Disease Missing "LLN - " added after "<" in middle of definition. Grade 4 Ejection fraction decreased Initial blank space removed from start of definition. 46 AE Grades marked as inapplicable ("-") Initial blank space(s) removed from before the "-" indicator. Revision 1 - 6/22/2009 MedDRA codes corrected for 2 AE terms: 10019663 Hepatic failure 10050528 Ejection fraction decreased