Primary cardioprotection with dexrazoxane in patients with childhood cancer who are expected to receive anthracyclines: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group

Baat, Esmée C de; Dalen, Elvira C. van; Mulder, Renée L.; Hudson, Melissa M.; Ehrhardt, Matthew J.; Engels, Frederike K.; Feijen, Elizabeth A M; Grotenhuis, Heynric B.; Leerink, Jan M.; Kapusta, Livia; Kaspers, Gertjan J.L.; Merkx, Remy; Mertens, Luc; Skinner, Roderick; Tissing, Wim J. E.; Vathaire, F. de; Nathan, Paul C.; Kremer, Leontien; Mavinkurve‐Groothuis, Annelies M. C.; Armenian, Saro H.

doi:10.1016/s2352-4642(22)00239-5

Cited by 29 publications

(17 citation statements)

References 51 publications

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“…As the most significant complications of AREN0321 were related to cardiac and pulmonary dysfunction, we hypothesize that the universal use of the cardioprotectant dexrazoxane 14 in our study, which was allowed but not recommended on AREN0321, may have contributed to the lack of grade 4 and 5 toxicities. Recent evidence and consensus‐based recommendations support more widespread use of dexrazoxane in pediatric oncology, so its inclusion as standard of care should be expected for future patients treated with VDC‐ICE 15–17 . However, future studies are needed to confirm the hypothesis of its benefit to these patients.…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence and consensus-based recommendations support more widespread use of dexrazoxane in pediatric oncology, so its inclusion as standard of care should be expected for future patients treated with VDC-ICE. [15][16][17] However, future studies are needed to confirm the hypothesis of its benefit to these patients. Additional supportive care, including administration of prophylactic infectious measures may have helped decrease infectious complications, but these were not administered in a standardized way.…”

Section: Discussionmentioning

confidence: 99%

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Tolerability of ifosfamide‐containing regimen in patients with high‐risk renal and INI‐1‐deficient tumors

Wong

Benedetti

Kao

et al. 2023

Pediatric Blood & Cancer

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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 nonhematologic 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

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tolerability of ifosfamide‐containing regimen in patients with high‐risk renal and INI‐1‐deficient tumors

Wong

Benedetti

Kao

et al. 2023

Pediatric Blood & Cancer

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“…Guidelines for the treatment of cardiac dysfunction in CCSs advocate management similar to that in children without cancer 8,9 . Dexrazoxane is probably the most effective cardioprotectant agent and is now recommended for use in protocols where cumulative doxorubicin dose is 250 mg/m 2 , but is not available in India 32 …”

Section: Discussionmentioning

confidence: 99%

“…8,9 Dexrazoxane is probably the most effective cardioprotectant agent and is now recommended for use in protocols where cumulative doxorubicin dose is 250 mg/m 2 , but is not available in India. 32 There are limitations to this study. A large number of children with Ewing sarcoma were ineligible, and hence were not included in the study cohort (Figure S2).…”

Section: Status Of Cardiac Functionmentioning

confidence: 90%

Cardiac function in pediatric Ewing sarcoma during and after treatment: A longitudinal study

Mande

Prasad

Srinivasan

et al. 2023

Pediatric Blood & Cancer

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Background: While anthracycline therapy has been shown to improve outcomes in Ewing sarcoma, it may be associated with severe and even fatal cardiac dysfunction.We evaluated the burden and determinants of cardiac dysfunction in pediatric Ewing sarcoma (pES).Methods: This retrospective study included children aged 0-18 years with pES treated at our center with the EFT 2001 protocol (anthracycline and cyclophosphamide containing regimen), with/without radiation therapy from January 2001 to December 2018. Cardiac dysfunction was defined as left ventricular (LV) ejection fraction with an absolute value <50%.Results: Amongst 650 eligible patients (median age at diagnosis 12 years and median follow-up duration 69 months), 85 (13%) developed cardiac dysfunction, at a median 13 months (range: 1-168 months). The cumulative incidence of cardiac dysfunction was 5.7% at 12 months, 12% at 2 years, 13% at 3 years, 14% at 5 years, and 15 % at 10 years. At a median follow-up duration of 25 (range: 3-212) months, 21 (24.7%) patients had normalization of LV function, whereas nine (10.6%) patients died of cardiac causes.Older age at diagnosis (7-12 years OR 5.1, p = .01, 13-18 years, OR 3.9, p = .03), female sex (OR 2.3, p = .004), undernutrition (OR 2.9, p = .001), and chest wall location (OR 8.7, p = .08) were risk factors for cardiac dysfunction. Conclusions:Children with Ewing sarcoma have a high incidence of cardiac dysfunction, which continues to develop even years after therapy, underlining the need for life-long surveillance. Undernourished children are at a higher risk for cardiac dysfunction and need stringent monitoring.

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“…Cancer Guideline Harmonization Group (IGHG) has developed an evidence-based clinical practice guideline for the use of dexrazoxane in children with cancer expected to receive anthracyclines. 3 Given the dose-dependent risk of anthracycline-induced cardiotoxicity, the guideline panel concluded that administration of dexrazoxane is reasonable in children who are expected to receive a cumulative doxorubicin or equivalent dose of at least 250 mg/m 2 and that clinicians and patients/families should weigh the cardioprotective effect of dexrazoxane against the possible harms, including subsequent neoplasms. Unfortunately, no recommendation could be formulated for cumulative doxorubicin or equivalent doses of less than 250 mg/m 2 , due to insufficient evidence to determine whether the risk of cardiotoxicity outweighs the possible risk of subsequent neoplasms.…”

Section: Using This Evidence the International Late Effects Of Childhoodmentioning

confidence: 99%

Comment on: Cardiotoxicity in children with cancer treated with anthracyclines: A position statement on dexrazoxane

Mavinkurve‐Groothuis

Baat

Feijen

et al. 2023

Pediatric Blood & Cancer

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Primary cardioprotection with dexrazoxane in patients with childhood cancer who are expected to receive anthracyclines: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group

Cited by 29 publications

References 51 publications

Tolerability of ifosfamide‐containing regimen in patients with high‐risk renal and INI‐1‐deficient tumors

Tolerability of ifosfamide‐containing regimen in patients with high‐risk renal and INI‐1‐deficient tumors

Cardiac function in pediatric Ewing sarcoma during and after treatment: A longitudinal study

Comment on: Cardiotoxicity in children with cancer treated with anthracyclines: A position statement on dexrazoxane

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