The randomised induction for high-risk neuroblastoma comparing COJEC and N5-MSKCC regimens: Early results from the HR-NBL1.5/SIOPEN trial.

Garaventa, Alberto; Pötschger, Ulrike; Valteau‐Couanet, Dominique; Castel, Victoria; Elliott, Martin; Ash, Susan; Chan, Godfrey Chi‐Fung; Laureys, Geneviève; Popović, Maja; Vettenranta, Kim; Balwierz, Walentyna; Schrøeder, Henrik; Owens, Cormac; Cesen, Maja; Papadakis, Vassilios; Trahair, Toby N.; Luksch, Roberto; Schleiermacher, Gudrun; Ambros, Peter F.; Ladenstein, Ruth

doi:10.1200/jco.2018.36.15_suppl.10507

Cited by 12 publications

(22 citation statements)

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“…A Cochrane review evaluating disease response and toxicities of rapid COJEC versus conventional induction therapy showed no difference in response and inconclusive data regarding toxicities [ 6 ]. A randomized trial of COJEC compared with the N5-MSKCC (Memorial Sloan Kettering Cancer Center) [ 7 ] regimen showed no differences in complete responses between the regimens but a lower frequency of toxicities with COJEC [ 8 ]. COJEC will thus remain the induction regimen for SIOPEN protocols.…”

Section: Treatmentmentioning

confidence: 99%

High-Risk Neuroblastoma Treatment Review

2018

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Neuroblastoma is the most common extracranial solid tumor in children. One subset, high-risk neuroblastoma, is very difficult to treat and requires multi-modal therapy. Intensification of therapy has vastly improved survival rates, and research is focused on novel treatments to further improve survival rates. The current treatment schema is divided into three stages—induction, consolidation, and maintenance. This review serves as an overview of the current treatment for high-risk neuroblastoma and a glimpse at current research for future therapy.

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Section: Treatmentmentioning

confidence: 99%

High-Risk Neuroblastoma Treatment Review

2018

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“…Half of patients have clinical high-risk disease at the time of diagnosis, defined as age greater than 18 months, the presence of distant metastases and/or amplification of the MYCN oncogene [1] . Despite intensification of conventional therapies in recent years approximately half of all children with high-risk neuroblastoma still die with relapsed/refractory disease [2] , [3] , [4] .…”

Section: Introductionmentioning

confidence: 99%

Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma

et al. 2020

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Background In neuroblastoma, genetic alterations in ATRX, define a distinct poor outcome patient subgroup. Despite the need for new therapies, there is a lack of available models and a dearth of pre-clinical research. Methods To evaluate the impact of ATRX loss of function (LoF) in neuroblastoma, we utilized CRISPR-Cas9 gene editing to generate neuroblastoma cell lines isogenic for ATRX . We used these and other models to identify therapeutically exploitable synthetic lethal vulnerabilities associated with ATRX LoF. Findings In isogenic cell lines, we found that ATRX inactivation results in increased DNA damage, homologous recombination repair (HRR) defects and impaired replication fork processivity. In keeping with this, high-throughput compound screening showed selective sensitivity in ATRX mutant cells to multiple PARP inhibitors and the ATM inhibitor KU60019. ATRX mutant cells also showed selective sensitivity to the DNA damaging agents, sapacitabine and irinotecan. HRR deficiency was also seen in the ATRX deleted CHLA-90 cell line, and significant sensitivity demonstrated to olaparib/irinotecan combination therapy in all ATRX LoF models. In-vivo sensitivity to olaparib/irinotecan was seen in ATRX mutant but not wild-type xenografts. Finally, sustained responses to olaparib/irinotecan therapy were seen in an ATRX deleted neuroblastoma patient derived xenograft. Interpretation ATRX LoF results in specific DNA damage repair defects that can be therapeutically exploited. In ATRX LoF models, preclinical sensitivity is demonstrated to olaparib and irinotecan, a combination that can be rapidly translated into the clinic. Funding This work was supported by Christopher's Smile, Neuroblastoma UK, Cancer Research UK, and the Royal Marsden Hospital NIHR BRC.

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“…The SIOPEN HR‐NBL1 trial compared RAPID COJEC (vincristine, carboplatin, etoposide, cisplatin, and cyclophosphamide) induction chemotherapy with the Memorial Sloan Kettering modified N7 regimen (cyclophosphamide, doxorubicin, vincristine, cisplatin, and etoposide). Preliminary results showed no difference in survival and metastatic response rates 47 . However, RAPID COJEC was less toxic than the modified N7 regimen, so this regimen was selected to be the SIOPEN reference induction regimen.…”

Section: Systemic Therapymentioning

confidence: 99%

“…Preliminary results showed no difference in survival and metastatic response rates. 47 However, RAPID COJEC was less toxic than the modified N7 regimen, so this regimen was selected to be the SIOPEN reference induction regimen. In the induction phase of the German (GPOH) NB2004-HR trial, patients were randomized between six N5 (cisplatin, vindesine, and etoposide)-N6 (vincristine, dacarbazine, ifosfamide, and doxorubicin) cycles or the experimental induction chemotherapy having two additional topotecan-based cycles (N8 [topotecan, cyclophosphamide, topotecan, and etoposide]-N5-N6 cycles).…”

Section: Europementioning

confidence: 99%

Neuroblastoma

Chung

Boterberg

Lucas

et al. 2021

Pediatric Blood & Cancer

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The survival of patients with high‐risk neuroblastoma has improved significantly with the use of intensive multimodality treatment regimens, including chemotherapy, surgery, radiation therapy, myeloablative chemotherapy followed by stem cell rescue, and immunotherapy. This report summarizes the current treatment strategies used in the COG and SIOP for children with neuroblastoma. The improved global collaboration and the adoption of a uniform International Neuroblastoma Risk Group Staging System will help facilitate comparison of homogeneous pretreatment cohorts across clinical trials. Future research strategies regarding the indications for and dosages of radiation therapy to the primary and metastatic sites, and the integration of meta‐iodobenzyl guanidine therapy into the multimodal treatment program, are discussed.

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The randomised induction for high-risk neuroblastoma comparing COJEC and N5-MSKCC regimens: Early results from the HR-NBL1.5/SIOPEN trial.

Cited by 12 publications

References 0 publications

High-Risk Neuroblastoma Treatment Review

High-Risk Neuroblastoma Treatment Review

Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma

Neuroblastoma

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