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Chemotherapy Intensification by Interval Compression in Localized Ewing Sarcoma Family Tumors (ESFT) RB Womer, DC West, MD Krailo, PS Dickman, B Pawel,

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Presentation on theme: "Chemotherapy Intensification by Interval Compression in Localized Ewing Sarcoma Family Tumors (ESFT) RB Womer, DC West, MD Krailo, PS Dickman, B Pawel,"— Presentation transcript:

1 Chemotherapy Intensification by Interval Compression in Localized Ewing Sarcoma Family Tumors (ESFT) RB Womer, DC West, MD Krailo, PS Dickman, B Pawel, for the Children’s Oncology Group AEWS0031 Committee

2 AEWS0031 Design RANDOMIZERANDOMIZE VCR Dox CPM IFOS ETOP VCR Dox CPM IFOS ETOP VCR Dox CPM IFOS ETOP VCR Dox CPM IFOS ETOP Regimen A q3w x 2 Local Control q2w x 3 q3w x 5 q2w x 4 Regimen B

3 AEWS0031 Accrual Open May 2001-August 2005 Localized ESFT, age <50 years Total 587 patients enrolled –19 ineligible 12 wrong diagnosis 4 metastases at diagnosis 3 treatment before enrollment or randomization –Thus 568 eligible patients

4 AEWS0031 Accrual by Strata* StratumStratum nameAccrual 1< 17y, non-pelvic419 2< 17y, pelvic93 3> 18y, non-pelvic57 4> 18y, pelvic18 *ineligible patients included

5 AEWS0031 Randomization Age Group | Standard Intensive | Total -----------+----------------------+---------- -17 | 253 248 | 501 18+ | 31 36 | 67 -----------+----------------------+---------- Total | 284 284 | 568 | Standard Intensive | Total -----------+----------------------+---------- Non-Pelvic | 237 243 | 480 Pelvic | 47 41 | 88 -----------+----------------------+---------- Total | 284 284 | 568

6 AEWS0031 Patient Characteristics CharacteristicsStandard (N=284) Intensive (N=284) Age at Study Entry Median (Range)12 (0-33)13 (0-45) Gender Male154 (54%) Female130 (46%) Race White252 (89%)250 (88%) Black8 (3%)6(2%) Other14 (5%)16 (6%) Not Reported10 (4%)12 (4%) Laboratory Information ESR (mm/hr)31.4 (32.2)32.9 (28.3) LDH (IU/l)448.2 (414.0)451.5 (437.2) Pleural Effusions at Diagnosis19 (8%)21 (9%) Gross tumor resection prior to start of chemotherapy47 (17%)48 (17%)

7 AEWS0031 Patient Characteristics 2 CharacteristicsStandard (N=284) Intensive (N=284) Primary tumor site Skull, maxilla, mandible15 (5.5%)12 (4.3%) C, T, L Vertebrae11 (3.9%)28 (9.9%) Sacrum16 (5.6%)8 (2.8%) Ribs, Sternum29 (10.3%)25 (8.9%) Scapula, clavicle14 (4.9%)14 (5.0%) Humerus13 (4.6%)12 (4.2%) Ulna, Radius7 (2.5%) Phalanges (Fingers)0 (0%)1 (0.4%) Pelvis31 (11%)33 (11.6%) Femur32 (11.3%)27 (9.5%) Patella1 (0.4%) Tibia, fibula40 (14.1%)33 (11.1%) Bones of feet8 (2.9%)7 (2.5%) Soft Tissue67 (23.6%)76 (26.8%) Fracture at primary site9 (3.5%)14 (5.5%)

8 AEWS0031 Chemotherapy Cycle Lengths Standard (A)Intensive (B) Mean (days)23.318.5 Median (days)2115

9 p=0.029

10 p=0.026

11 0.00 0.25 0.50 0.75 1.00 Estimated Proportion Event-Free 0246 Years -4 5-9 10-14 15+ Age Group By Age at Dx EFS for All Eligible Patients

12

13

14 AEWS0031 Regimens and Age Reg B Reg A

15 AEWS0031 Infectious Toxicities Toxicity Type Randomized Treatment Assignment StandardIntensive Percent Number of Courses with Toxicity Total Number of CoursesPercent Number of Courses with Toxicity Total Number of Courses Wound-infectious 1.03536140.7273623 Colitis 0.2836140.153623 Typhlitis 0.0136140.3113623 Catheter-related infection 1.55436141.0383623 Febrile neutropenia (fever of unknown origin) 6.122136147.42693623 Infection with grade 3 or 4 neutropenia 4.616636144.81733623 Infection with unknown ANC 0.2636140.123623 Infection without neutropenia 2.28036142.0723623 Infection/Febrile Neutropenia - Other 0.31136140.3113623

16 AEWS0031 Other Toxicities Toxicity Type Randomized Treatment Assignment StandardIntensive Perce n t Number of Course with Toxicit y Total Nu mbe r of Cou rses Perce n t Number of Cou rse with Toxi city Total Num ber of Cour ses Transfusion: Platelets 2.69336144.81733623 Transfusion: pRBCs 5.620136148.93223623 Cardiac left ventricular function 0.013623 Hypotension 0.82936140.5183623 Fatigue (lethargy, malaise, asthenia) 0.31236140.263623 Fever (in the absence of neutropenia) 0.1436140.143623 Weight loss 0.1436140.133623 Constitutional Symptoms - Other 0.1236140.123623 Hand-foot skin reaction 0.293623 Radiation dermatitis 0.41336140.273623 Rash/desquamation 0.1336140.283623 Wound-infectious 1.03536140.7273623 Wound-non infectious 0.1436140.123623

17 AEWS0031 Hospital Days by Regimen Treatmentp-value 1 Standard (n=237) Intensive (n=239) Mean (SD)68.5 (26.9)69.9 (29.1)0.46 Median (Range)66 (5, 178)67 (5, 267)

18 AEWS0031 Events 123 relapses 13 SMN (7 Regimen A, 6 Regimen B) –9 secondary AML/MDS 4 Regimen A, 5 Regimen B –3 secondary OS –1 Diffuse large B cell lymphoma 1 toxic death 1 narcotic overdose 4 other deaths as first event –Incomplete data or not evaluated

19 AEWS0031 Conclusions So Far Every-two-week chemotherapy is more effective than every three week chemotherapy for localized Ewing sarcoma, with similar toxicity –Unless one is 18 or older

20 AEWS0031 Things to Do (1) Data cleanup –Check deaths as first events –Review soft tissue primary sites –Check sites of first relapse –Compile interval compression data

21 AEWS0031 Things to Do (2) Analyses –Bone v. soft tissue Overall By regimen Bone surface ES? –Regimen and primary site –Primary tumor treatment –Dose intensification achieved Relationship to outcome –Patterns of relapse Relationship to regimen Correlative biology –~160 patients on AEWS0031 and bio studies

22 AEWS0031 Study Committee Rick Womer Dan West Mark Krailo Karen Albritton Christie Lee Powell Chris Denny Meeni Devidas Paul Dickman Doug Hawkins Bruce Pawel John Dormans John Healey Carol Kotsubo Karen Marcus Kathleen Patterson Scott Sailer Ted Zwerdling Loreen MacIsaac Brenda Ennis Mark Gebhardt Holcombe Grier James Meyer Greg Griffin Linda Granowetter Special thanks to Chris Williams-Hughes, Celeste Sabinske, Biljana Georgievska and Steven Jong.


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