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Integrating Irinotecan in standard chemotherapy: a novel dose density combination for High-Risk pediatric Sarcomas
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  • Gianni Bisogno,
  • Andrea Ferrari,
  • Arianna Tagarelli,
  • Silvia Sorbara,
  • Stefano Chiaravalli,
  • Elena Poli,
  • Giovanni Scarzello,
  • Federica De Corti,
  • Michela Casanova,
  • Maria Carmen Affinita
Gianni Bisogno
Padua University Hospital
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Andrea Ferrari
Fondazione IRCCS Istituto Nazionale dei Tumori
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Arianna Tagarelli
Padua University Hospital
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Silvia Sorbara
Padua University Hospital
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Stefano Chiaravalli
Fondazione IRCCS Istituto Nazionale dei Tumori
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Elena Poli
Padua University Hospital
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Giovanni Scarzello
Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico
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Federica De Corti
Padua University Hospital
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Michela Casanova
Fondazione IRCCS Istituto Nazionale dei Tumori
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Maria Carmen Affinita
Padua University Hospital
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Abstract

BACKGROUND: Irinotecan is a drug active against pediatric sarcomas with a toxicity profile that theoretically allows for its association with more myelotoxic drugs. We examined the feasibility of a dose-density strategy integrating irinotecan in standard chemotherapy regimens for patients with high-risk sarcomas. METHODS: Between November 2013 and January 2020, 23 patients < 21 years old with metastatic (11 children) or recurrent (12 children) sarcomas were treated with 9 IrIVA/IrVAC cycles. All newly-diagnosed patients received IrIVA (ifosfamide 3g/m2 on days 1 and 2, vincristine 1.5 mg/m2 on day 1, actinomycin D 1.5 mg/m2 on day 1, irinotecan 20 mg/m2 for 5 consecutive days starting on day 8). Two relapsed patients received IrIVA and 10 IrVAC (cyclophosphamide 1.5 g/m2 on day 1 instead of ifosfamide). Feasibility was assessed in terms of toxicity and time to complete the treatment. RESULTS: 17 rhabdomyosarcomas, 4 Ewing sarcomas, 2 desmoplastic round cell tumors received a total of 181 cycles (range 2-10). Grade 4 neutropenia occurred in 62.4% of the cycles. 13 patients had febrile neutropenia. Diarrhea occurred in 14 cycles. The median time to complete the treatment was 195 days (range 170-231), 83.4% of cycles were administered on time or with a delay <1 week. With a median follow-up of 2.6 years (range 0.2-5.0), 12 patients are alive, 9 complete remissions, 3 with the disease. Conclusions: A dose density strategy combining irinotecan with standard chemotherapy is feasible. This approach will be investigated in the next trial coordinated by the European pediatric Soft tissue sarcoma Study Group.

Peer review status:Published

18 Oct 2020Submission Checks Completed
18 Oct 2020Assigned to Editor
18 Oct 2020Submitted to Pediatric Blood & Cancer
19 Oct 2020Reviewer(s) Assigned
17 Nov 2020Review(s) Completed, Editorial Evaluation Pending
17 Nov 2020Editorial Decision: Revise Minor
13 Dec 20201st Revision Received
13 Dec 2020Submission Checks Completed
13 Dec 2020Assigned to Editor
14 Dec 2020Reviewer(s) Assigned
06 Jan 2021Review(s) Completed, Editorial Evaluation Pending
07 Jan 2021Editorial Decision: Accept
10 Mar 2021Published in Pediatric Blood & Cancer. 10.1002/pbc.28951