Front-Line Window Therapy with Temozolomide and Irinotecan in Patients with Primary Disseminated Multifocal Ewing Sarcoma: Results of the ISG/AIEOP EW-2 Study

Asaftei, Sebastian Dorin; Puma, Nadia; Paioli, Anna; Petraz, Marco; Morosi, Carlo; Podda, Marta; Tamburini, Angela; Palmerini, Emanuela; Coccoli, Luca; Grignani, Giovanni; Manzitti, Carla; Bertulli, Rossella; Leonardis, Francesco De; Rabusin, Marco; Campello, Anna; Tirtei, Elisa; Picci, Piero; Prete, Arcangelo; Longhi, Alessandra; Luksch, Roberto

doi:10.3390/cancers13123046

Cited by 9 publications

(5 citation statements)

References 24 publications

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“…An induction chemotherapy was performed in all patients: n = 7 cases were treated according to the Italian Sarcoma Group (ISG) and Scandinavian Sarcoma Group (SSG) trial ISG/SSG III [ 21 ], n = 3 cases according to the ISG and the Italian Association of Pediatric Hematology and Oncology (AIEOP) trial ISG/AIEOP EW-1 [ 22 ], n = 4 cases according to the ISG and the AIEOP trial ISG/AIEOP EW2 [ 23 ], and n = 1 case according to the ISG/AIEOP EW Oss protocol.…”

Section: Resultsmentioning

confidence: 99%

Primary Chest Wall Ewing Sarcoma: Treatment and Long-Term Results

Salimbene,

Viggiano,

Muratori

et al. 2024

Life

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Objective: The aim of the study is to evaluate early and long-term results of chest wall primary Ewing’s sarcoma patients treated in the time period February 2000–February 2023 by a multidisciplinary approach. Methods: We retrospectively reviewed the medical records of patients who underwent chest wall resection for a primary tumor. Treatment approach, extent of resection, 30-day mortality, overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were analyzed. Results: Overall, n = 15 consecutive patients were treated for chest wall primary Ewing’s sarcoma. A median of n = 3 ribs was resected with a median of n = 2 ribs adjacent to the lesion. Resections were extended to the adjacent structures in n = 5 patients (33.3%). In all cases, we performed a prosthetic reconstruction, associated with muscle flap (n = 10, 66.6%) or with rigid titanium bars and muscle flap (n = 6, 40%). A radical resection was accomplished in n = 13 patients (84.6%). The median surgical time was 310 ± 120 min; median hospitalization was 7.8 ± 1.9 days. Post-operative mortality was zero. We recorded n = 4 (30.7%) post-operative complication. The median follow-up (FU) was 26 months. Moreover, 5-year overall and event-free survival were 52% and 48%, respectively. Conclusions: This case series confirms the benefit of the multidisciplinary approach for Ewing sarcomas in early and long-term results.

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Section: Resultsmentioning

confidence: 99%

Primary Chest Wall Ewing Sarcoma: Treatment and Long-Term Results

Salimbene,

Viggiano,

Muratori

et al. 2024

Life

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“…IT has also been evaluated in several retrospective studies in patients with advanced, relapsed, or recurrent Ewing sarcoma, and the ORRs in the studies have ranged from 29% to 63%, showing that IT is effective and feasible for this patient population [66][67][68][69][70]. In a phase 2 study with front-line IT in patients with primary disseminated Ewing sarcoma (N = 34), while two courses of IT showed promising ORR (59%) and CBR (91%), there was no impact on event-free survival [71].…”

Section: Phase 2 Clinical Trials and Other Studies In Patients With S...mentioning

confidence: 99%

Current Role of Topoisomerase I Inhibitors for the Treatment of Mesenchymal Malignancies and Their Potential Future Use as Payload of Sarcoma-Specific Antibody-Drug Conjugates

Schöffski,

Wang,

Schöffski

et al. 2023

Oncol Res Treat

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Background: Topoisomerase I is an enzyme that plays a crucial part in DNA replication and transcription by the relaxation of supercoiled double-stranded DNA. Topoisomerase I inhibitors bind to the topoisomerase I cleavage complex, thereby stabilizing it and preventing the religation of the DNA strands, leading to DNA damage, cell cycle arrest, and apoptosis. Various topoisomerase I inhibitors have been evaluated in solid tumors, and irinotecan and topotecan have been approved for the treatment of epithelial malignancies. None of them have been approved for sarcoma, a diverse group of rare solid tumors with an unmet need for effective treatments. Summary: Topoisomerase I inhibitors have been evaluated in preclinical studies as single agents or in combination in solid tumors, some of which have included sarcomas where activity was observed. Clinical trials evaluating topoisomerase I inhibitors for the treatment of sarcoma have shown limited efficacy as monotherapy. In combination with other cytotoxic agents, topoisomerase I inhibitors have become part of clinical routine in selected sarcoma subtypes. Regimens such as irinotecan/vincristine/temozolomide are used in relapsed rhabdomyosarcoma, irinotecan/temozolomide and vincristine/topotecan/cyclophosphamide are commonly given in refractory Ewing sarcoma, and topotecan/carboplatin showed some activity in advanced soft tissue sarcoma. This review provides an overview of key studies with topoisomerase I inhibitors for the treatment of sarcoma. Topoisomerase I inhibitors are currently also being assessed as “payloads” for antibody-drug conjugates (ADCs), allowing for the targeting of specific antigen-expressing tumor cells and the delivery of the inhibitor directly to the tumor cells with the potential of enhancing therapeutic efficacy while minimizing systemic toxicity. Here, we also provide a brief overview on topoisomerase I-ADCs. Key Message: Topoisomerase I inhibitors are an important component of some systemic therapies for selected sarcomas and have potent cytotoxic properties and pharmacological characteristics that make them relevant candidates as payloads for the development of sarcoma-specific ADCs. ADCs are antibody-based targeted agents allowing for efficient and specific delivery of a given drug to the tumor cell. Topoisomerase I-ADCs are a novel targeted delivery approach which may have the potential to improve the therapeutic index of topoisomerase I inhibitors in the treatment of sarcoma and warrants investigation in a broad variety of mesenchymal malignancies.

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“…Cytotoxic chemotherapy regimens for Ewing sarcoma were actively investigated until recently. Temozolomide-based salvage chemotherapy was evaluated prospectively for approximately 20 years and showed promising objective responses [ 70 , 71 , 72 , 73 , 74 ], and a temozolomide-based regimen was under investigation as a first-line therapy [ 75 ]. Topotecan-based therapies also provided objective clinical responses [ 24 , 76 , 77 ], but the use of topotecan-based combination chemotherapy as a first-line treatment failed to show survival benefit in a phase III trial [ 78 ].…”

Section: Ewing Sarcoma Of Bonementioning

confidence: 99%

Challenges of Systemic Therapy Investigations for Bone Sarcomas

Nakano

2022

IJMS

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Bone sarcoma is a rare component of malignant solid tumors that accounts for only ~0.2% of malignancies. Bone sarcomas present various histological types, and genomic mutations differ markedly by the histological types. Although there are vast mutations in various bone sarcomas, most of them are non-actionable, and even potential targetable mutations that are actionable targets in other malignancies have not shown the appropriate responses in clinical trials for bone sarcomas. Investigations of new systemic therapy, including molecular targeted therapies for bone sarcomas, have thus not progressed like those for other solid tumors. Another problem is that high rates of pediatric/adolescent and young adult patients have bone sarcomas such as osteosarcoma, and patient recruitment for clinical trials (especially randomized trials) is challenging. For pediatric patients, evaluations of tolerability and appropriate dose modifications of new drugs are needed, as their findings could provide the threshold for investigating new drugs for bone sarcomas. To solve these problems, improvements in registry systems, real world data, and pediatric extrapolation have been attempted. We review the issues regarding targeted drug investigations for bone sarcomas, focusing on the current clinical evidence and efforts to resolve these issues.

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Front-Line Window Therapy with Temozolomide and Irinotecan in Patients with Primary Disseminated Multifocal Ewing Sarcoma: Results of the ISG/AIEOP EW-2 Study

Cited by 9 publications

References 24 publications

Primary Chest Wall Ewing Sarcoma: Treatment and Long-Term Results

Primary Chest Wall Ewing Sarcoma: Treatment and Long-Term Results

Current Role of Topoisomerase I Inhibitors for the Treatment of Mesenchymal Malignancies and Their Potential Future Use as Payload of Sarcoma-Specific Antibody-Drug Conjugates

Challenges of Systemic Therapy Investigations for Bone Sarcomas

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