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Tolerability of ifosfamide-containing regimen in patients with high-risk renal and INI-1-deficient tumors
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  • Chris I. Wong,
  • Daniel Benedetti,
  • Pei-Chi Kao,
  • Clement Ma,
  • Karen Marcus,
  • Elizabeth Mullen
Chris I. Wong
University Hospitals Rainbow Babies & Children's Hospital

Corresponding Author:[email protected]

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Daniel Benedetti
Vanderbilt Department of Pediatrics
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Pei-Chi Kao
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
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Clement Ma
Centre for Addiction and Mental Health
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Karen Marcus
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
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Elizabeth Mullen
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
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Background: Outcomes for children with high-risk renal (HRR) and INI-1-deficient (INI-) tumors are unacceptably poor. Concerns about excessive toxicity – as many are infants and/or undergo nephrectomy – have resulted in decreased chemotherapy dosing and omission of the nephrotoxic drug ifosfamide in collaborative group studies. As cause of death for children with these cancers remains overwhelmingly more from progressive disease rather than treatment toxicity, we examined the tolerability of an intensive ifosfamide-containing-regimen. Procedure: Retrospective review of children with HRR/INI- tumors treated at a single institution with vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, carboplatin, etoposide (VDC-ICE) from 2006-2016. The primary outcome was regimen tolerability including kidney injury and grade 3-5 non-hematologic toxicities. Results: Fourteen patients with a median age of 1.7 years (range 0.1-10.5) treated with VDC-ICE were identified. Diagnosis included malignant rhabdoid tumor (n=9) [primary renal (n=2)]; diffuse anaplastic Wilms tumor (n=3); clear cell sarcoma of the kidney (n=1); and anaplastic chordoma (n=1). All children with primary renal tumors (43%) underwent complete (n=5) or partial nephrectomy (n=1) before chemotherapy. Nine (64%) completed all intended cycles of chemotherapy; n=5 (36%) did not due to disease progression. Unplanned hospitalizations occurred in 13 (93%) patients, most commonly for febrile neutropenia. No patient experienced severe organ toxicity, diminished renal function, treatment discontinuation due to toxicities, or treatment-related death. Conclusions: In children with HRR/INI- tumors, VDC-ICE chemotherapy was well-tolerated without excessive toxicities, even amongst young patients with solitary kidneys. Concerns about toxicity should not preclude an intensive ifosfamide-containing regimen from use in future trials in this population.
31 Jan 2023Submission Checks Completed
31 Jan 2023Assigned to Editor
31 Jan 2023Submitted to Pediatric Blood & Cancer
31 Jan 2023Review(s) Completed, Editorial Evaluation Pending
01 Feb 2023Reviewer(s) Assigned
06 Feb 2023Editorial Decision: Revise Minor
18 Apr 20231st Revision Received
18 Apr 2023Submission Checks Completed
18 Apr 2023Assigned to Editor
24 Apr 2023Review(s) Completed, Editorial Evaluation Pending
24 Apr 2023Reviewer(s) Assigned
25 Apr 2023Editorial Decision: Accept