Irinotecan and temozolomide for Ewing sarcoma

The memorial sloan-kettering experience

Denise A. Casey, Leonard H. Wexler, Melinda S. Merchant, Alexander Ja-Ho Chou, Pamela R. Merola, Anita P. Price, Paul A. Meyers

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Background. The prognosis for recurrent/progressive Ewing sarcoma (ES) remains poor. Pre-clinical, adult phase I and II trials have demonstrated the combination of irinotecan and temozolomide to have schedule-dependent synergy and significant antitumor activity. A pediatric phase I trial has shown this regimen to be safe and active in advanced ES. Procedure. We conducted a retrospective chart review to identify patients with recurrent/progressive ES treated with irinotecan [20 mg/m2/day x 5(x2)] and temozolomide (100 mg/ m2/day x 5) in our institution. The best response achieved, time to progression (TTP), and associated toxicities were recorded. Results. Twenty patients received a total of 154 cycles of therapy. Of 19 evaluable patients, there were 5 complete and 7 partial responses (a 63% overall objective response). Median TTP for 20 evaluable patients with recurrent/progressive ES was 8.3 months; for the subset of 14 patients with recurrent ES, it was 16.2 months. Median TTP was better for patients who sustained a 2-year first remission than for those who relapsed <24 months from diagnosis and for patients with primary localized vs. metastatic disease. Significant toxicities included grade 3 diarrhea (7 cycles), grade 3 colitis (1 cycle), grade 3 pneumonitis in one patient receiving concurrent whole-lung RT, grade 3-4 neutropenia (19 cycles), and grade 3-4 thrombocytopenia (16 cycles). Conclusions. Irinotecan and temozolomide is a well-tolerated and active regimen for recurrent/progressive ES. Prospective trials are necessary to define the role of this regimen in newly diagnosed ES.

Original languageEnglish (US)
Pages (from-to)1029-1034
Number of pages6
JournalPediatric Blood and Cancer
Volume53
Issue number6
DOIs
StatePublished - Dec 8 2009
Externally publishedYes

Fingerprint

irinotecan
temozolomide
Ewing's Sarcoma
Phase II Clinical Trials
Clinical Trials, Phase I
Colitis
Neutropenia

Keywords

  • Ewing sarcoma
  • Irinotecan
  • Temozolomide

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Casey, D. A., Wexler, L. H., Merchant, M. S., Chou, A. J-H., Merola, P. R., Price, A. P., & Meyers, P. A. (2009). Irinotecan and temozolomide for Ewing sarcoma: The memorial sloan-kettering experience. Pediatric Blood and Cancer, 53(6), 1029-1034. https://doi.org/10.1002/pbc.22206

Irinotecan and temozolomide for Ewing sarcoma : The memorial sloan-kettering experience. / Casey, Denise A.; Wexler, Leonard H.; Merchant, Melinda S.; Chou, Alexander Ja-Ho; Merola, Pamela R.; Price, Anita P.; Meyers, Paul A.

In: Pediatric Blood and Cancer, Vol. 53, No. 6, 08.12.2009, p. 1029-1034.

Research output: Contribution to journalArticle

Casey, DA, Wexler, LH, Merchant, MS, Chou, AJ-H, Merola, PR, Price, AP & Meyers, PA 2009, 'Irinotecan and temozolomide for Ewing sarcoma: The memorial sloan-kettering experience', Pediatric Blood and Cancer, vol. 53, no. 6, pp. 1029-1034. https://doi.org/10.1002/pbc.22206
Casey, Denise A. ; Wexler, Leonard H. ; Merchant, Melinda S. ; Chou, Alexander Ja-Ho ; Merola, Pamela R. ; Price, Anita P. ; Meyers, Paul A. / Irinotecan and temozolomide for Ewing sarcoma : The memorial sloan-kettering experience. In: Pediatric Blood and Cancer. 2009 ; Vol. 53, No. 6. pp. 1029-1034.
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abstract = "Background. The prognosis for recurrent/progressive Ewing sarcoma (ES) remains poor. Pre-clinical, adult phase I and II trials have demonstrated the combination of irinotecan and temozolomide to have schedule-dependent synergy and significant antitumor activity. A pediatric phase I trial has shown this regimen to be safe and active in advanced ES. Procedure. We conducted a retrospective chart review to identify patients with recurrent/progressive ES treated with irinotecan [20 mg/m2/day x 5(x2)] and temozolomide (100 mg/ m2/day x 5) in our institution. The best response achieved, time to progression (TTP), and associated toxicities were recorded. Results. Twenty patients received a total of 154 cycles of therapy. Of 19 evaluable patients, there were 5 complete and 7 partial responses (a 63{\%} overall objective response). Median TTP for 20 evaluable patients with recurrent/progressive ES was 8.3 months; for the subset of 14 patients with recurrent ES, it was 16.2 months. Median TTP was better for patients who sustained a 2-year first remission than for those who relapsed <24 months from diagnosis and for patients with primary localized vs. metastatic disease. Significant toxicities included grade 3 diarrhea (7 cycles), grade 3 colitis (1 cycle), grade 3 pneumonitis in one patient receiving concurrent whole-lung RT, grade 3-4 neutropenia (19 cycles), and grade 3-4 thrombocytopenia (16 cycles). Conclusions. Irinotecan and temozolomide is a well-tolerated and active regimen for recurrent/progressive ES. Prospective trials are necessary to define the role of this regimen in newly diagnosed ES.",
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AU - Chou, Alexander Ja-Ho

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AU - Price, Anita P.

AU - Meyers, Paul A.

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