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Chemotherapy Intensification by Interval Compression in Localized Ewing Sarcoma Family Tumors (ESFT)

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. VCR Dox CPM. VCR Dox CPM. VCR Dox CPM. VCR Dox CPM. IFOS ETOP. IFOS ETOP.

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Chemotherapy Intensification by Interval Compression in Localized Ewing Sarcoma Family Tumors (ESFT)

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

  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* *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

  7. AEWS0031 Patient Characteristics 2

  8. AEWS0031Chemotherapy Cycle Lengths

  9. p=0.029

  10. p=0.026

  11. EFS for All Eligible Patients By Age at Dx 1.00 0.75 Age Group -4 5-9 0.50 Estimated Proportion Event-Free 10-14 15+ 0.25 0.00 0 2 4 6 Years

  12. Survival for All Eligible Patients By Age at Dx 1.00 0.75 Age Group -4 Estimated Proportion Surviving 0.50 5-9 10-14 15+ 0.25 0.00 0 2 4 6 Years

  13. 1.00 1.00 0.75 0.75 Age Group Age Group -17 Years -17 Years 0.50 0.50 18+ Years 18+ Years Estimated Proportion Event-Free Estimated Proportion Event-Free 0.25 0.25 0.00 0.00 0 0 2 2 4 4 6 6 Years Years AEWS0031 Regimens and Age Reg B Reg B Reg A

  14. AEWS0031 Infectious Toxicities

  15. AEWS0031 Other Toxicities

  16. AEWS0031 Hospital Days by Regimen

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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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