Pilot Study of Adding Vincristine, Topotecan, and Cyclophosphamide to Interval-Compressed Chemotherapy in Newly Diagnosed Patients With Localized Ewing Sarcoma: A Report From the Children's Oncology Group

Leo Mascarenhas, Judy L. Felgenhauer, Mason C. Bond, Doojduen Villaluna, Joseph Dominic Femino, Nadia N. Laack, Sarangarajan Ranganathan, James Meyer, Richard B. Womer, Richard Gorlick, Mark D. Krailo, Neyssa Marina

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: The combination of topotecan and cyclophosphamide is active in relapsed Ewing sarcoma family of tumors (ESFT). The feasibility of adding these agents combined with vincristine (vincristine-topotecan-cyclophosphamide [VTc]) to standard five-drug chemotherapy with vincristine-doxorubicin-cyclophosphamide (VDC) and ifosfamide-etoposide (IE) administered in an interval-compressed (2-week instead of 3-week intervals) schedule was investigated. Procedure: Newly diagnosed patients with localized ESFT < 31 years, with good performance status and adequate organ function were eligible. Seventeen alternating cycles of chemotherapy with VTc, VDC, and IE were administered at 2-week intervals. Local control (LC) of the primary tumor occurred following six cycles. Primary endpoints were the ability to deliver chemotherapy in an interval-compressed schedule, and the rate of grade 3 or greater nonhematologic toxicity and grade 4 hematologic toxicity, which delayed chemotherapy by ≥2 weeks. Secondary endpoints were event-free survival (EFS) and overall survival (OS). Results: Thirty-five patients with a median age of 11 years were enrolled. The mean time to last dose of chemotherapy prior to LC was 12.6 ± 1.4 weeks and 45.5% of patients received intended chemotherapy without any delay prior to LC. There were no toxic deaths or unexpected toxicities. Five-year EFS was 79.6% (95% confidence interval [CI]: 61.8-89.7%) and 5-year OS was 88% (95% CI: 71.4-95.3%). Conclusions: The addition of VTc to standard therapy was tolerable with sufficient interval compression compared to historical standard 3-week cycles.

Original languageEnglish (US)
Pages (from-to)493-498
Number of pages6
JournalPediatric Blood and Cancer
Volume63
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

Topotecan
Ewing's Sarcoma
Vincristine
Cyclophosphamide
Drug Therapy
Ifosfamide
Etoposide
Doxorubicin
Disease-Free Survival
Appointments and Schedules
Confidence Intervals
Neoplasms
Aptitude
Survival
Poisons
Pharmaceutical Preparations

Keywords

  • Cyclophosphamide
  • Dose dense
  • Ewing sarcoma
  • Interval compression
  • PNET
  • Topotecan

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)
  • Hematology
  • Oncology

Cite this

Pilot Study of Adding Vincristine, Topotecan, and Cyclophosphamide to Interval-Compressed Chemotherapy in Newly Diagnosed Patients With Localized Ewing Sarcoma : A Report From the Children's Oncology Group. / Mascarenhas, Leo; Felgenhauer, Judy L.; Bond, Mason C.; Villaluna, Doojduen; Femino, Joseph Dominic; Laack, Nadia N.; Ranganathan, Sarangarajan; Meyer, James; Womer, Richard B.; Gorlick, Richard; Krailo, Mark D.; Marina, Neyssa.

In: Pediatric Blood and Cancer, Vol. 63, No. 3, 01.03.2016, p. 493-498.

Research output: Contribution to journalArticle

Mascarenhas, L, Felgenhauer, JL, Bond, MC, Villaluna, D, Femino, JD, Laack, NN, Ranganathan, S, Meyer, J, Womer, RB, Gorlick, R, Krailo, MD & Marina, N 2016, 'Pilot Study of Adding Vincristine, Topotecan, and Cyclophosphamide to Interval-Compressed Chemotherapy in Newly Diagnosed Patients With Localized Ewing Sarcoma: A Report From the Children's Oncology Group', Pediatric Blood and Cancer, vol. 63, no. 3, pp. 493-498. https://doi.org/10.1002/pbc.25837
Mascarenhas, Leo ; Felgenhauer, Judy L. ; Bond, Mason C. ; Villaluna, Doojduen ; Femino, Joseph Dominic ; Laack, Nadia N. ; Ranganathan, Sarangarajan ; Meyer, James ; Womer, Richard B. ; Gorlick, Richard ; Krailo, Mark D. ; Marina, Neyssa. / Pilot Study of Adding Vincristine, Topotecan, and Cyclophosphamide to Interval-Compressed Chemotherapy in Newly Diagnosed Patients With Localized Ewing Sarcoma : A Report From the Children's Oncology Group. In: Pediatric Blood and Cancer. 2016 ; Vol. 63, No. 3. pp. 493-498.
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abstract = "Background: The combination of topotecan and cyclophosphamide is active in relapsed Ewing sarcoma family of tumors (ESFT). The feasibility of adding these agents combined with vincristine (vincristine-topotecan-cyclophosphamide [VTc]) to standard five-drug chemotherapy with vincristine-doxorubicin-cyclophosphamide (VDC) and ifosfamide-etoposide (IE) administered in an interval-compressed (2-week instead of 3-week intervals) schedule was investigated. Procedure: Newly diagnosed patients with localized ESFT < 31 years, with good performance status and adequate organ function were eligible. Seventeen alternating cycles of chemotherapy with VTc, VDC, and IE were administered at 2-week intervals. Local control (LC) of the primary tumor occurred following six cycles. Primary endpoints were the ability to deliver chemotherapy in an interval-compressed schedule, and the rate of grade 3 or greater nonhematologic toxicity and grade 4 hematologic toxicity, which delayed chemotherapy by ≥2 weeks. Secondary endpoints were event-free survival (EFS) and overall survival (OS). Results: Thirty-five patients with a median age of 11 years were enrolled. The mean time to last dose of chemotherapy prior to LC was 12.6 ± 1.4 weeks and 45.5{\%} of patients received intended chemotherapy without any delay prior to LC. There were no toxic deaths or unexpected toxicities. Five-year EFS was 79.6{\%} (95{\%} confidence interval [CI]: 61.8-89.7{\%}) and 5-year OS was 88{\%} (95{\%} CI: 71.4-95.3{\%}). Conclusions: The addition of VTc to standard therapy was tolerable with sufficient interval compression compared to historical standard 3-week cycles.",
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T1 - Pilot Study of Adding Vincristine, Topotecan, and Cyclophosphamide to Interval-Compressed Chemotherapy in Newly Diagnosed Patients With Localized Ewing Sarcoma

T2 - A Report From the Children's Oncology Group

AU - Mascarenhas, Leo

AU - Felgenhauer, Judy L.

AU - Bond, Mason C.

AU - Villaluna, Doojduen

AU - Femino, Joseph Dominic

AU - Laack, Nadia N.

AU - Ranganathan, Sarangarajan

AU - Meyer, James

AU - Womer, Richard B.

AU - Gorlick, Richard

AU - Krailo, Mark D.

AU - Marina, Neyssa

PY - 2016/3/1

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N2 - Background: The combination of topotecan and cyclophosphamide is active in relapsed Ewing sarcoma family of tumors (ESFT). The feasibility of adding these agents combined with vincristine (vincristine-topotecan-cyclophosphamide [VTc]) to standard five-drug chemotherapy with vincristine-doxorubicin-cyclophosphamide (VDC) and ifosfamide-etoposide (IE) administered in an interval-compressed (2-week instead of 3-week intervals) schedule was investigated. Procedure: Newly diagnosed patients with localized ESFT < 31 years, with good performance status and adequate organ function were eligible. Seventeen alternating cycles of chemotherapy with VTc, VDC, and IE were administered at 2-week intervals. Local control (LC) of the primary tumor occurred following six cycles. Primary endpoints were the ability to deliver chemotherapy in an interval-compressed schedule, and the rate of grade 3 or greater nonhematologic toxicity and grade 4 hematologic toxicity, which delayed chemotherapy by ≥2 weeks. Secondary endpoints were event-free survival (EFS) and overall survival (OS). Results: Thirty-five patients with a median age of 11 years were enrolled. The mean time to last dose of chemotherapy prior to LC was 12.6 ± 1.4 weeks and 45.5% of patients received intended chemotherapy without any delay prior to LC. There were no toxic deaths or unexpected toxicities. Five-year EFS was 79.6% (95% confidence interval [CI]: 61.8-89.7%) and 5-year OS was 88% (95% CI: 71.4-95.3%). Conclusions: The addition of VTc to standard therapy was tolerable with sufficient interval compression compared to historical standard 3-week cycles.

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KW - PNET

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