Clinical Activity of Pazopanib in Patients with Advanced Desmoplastic Small Round Cell Tumor

Menegaz, Brian A.; Cuglievan, Branko; Benson, Jalen; Camacho, Pamela; Lamhamedi-Cherradi, Salah-Eddine; Leung, Cheuk Hong; Warneke, Carla L.; Huh, Winston W.; Subbiah, Vivek; Benjamin, Robert S.; Patel, Shreyaskumar; Daw, Najat C.; Hayes‐Jordan, Andrea; Ludwig, Joseph A.

doi:10.1634/theoncologist.2017-0408

Cited by 39 publications

(27 citation statements)

References 38 publications

(44 reference statements)

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“…One patient who developed complications during adjuvant chemotherapy cycles was transitioned to six planned cycles of pazopanib, and is currently without evidence of disease at 20.7 months from initial diagnosis. Studies have demonstrated that pazopanib is active in DSRCT and well tolerated 39,40 . It remains unknown whether patients with DSRCT benefit from targeted agents, such as pazopanib in the upfront setting, or whether maintenance therapy may be beneficial.…”

Section: Discussionmentioning

confidence: 99%

The use of interval‐compressed chemotherapy with the addition of vincristine, irinotecan, and temozolomide for pediatric patients with newly diagnosed desmoplastic small round cell tumor

Liu

Collins

Greenzang

et al. 2020

Pediatric Blood & Cancer

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Background Desmoplastic small round cell tumor (DSRCT) is a rare aggressive sarcoma that affects children and young adults, and portends poor outcomes despite intensive multimodal treatment approaches. We report toxicity, response, and outcomes of patients with DSRCT treated with the addition of vincristine, irinotecan, and temozolomide (VIT) to interval‐compressed chemotherapy as per Children's Oncology Group ARST08P1. Methods All newly diagnosed pediatric patients with DSRCT treated at Dana‐Farber Cancer Institute and Boston Children's Hospital between 2014 and 2019 as per ARST08P1, Arm P2 with replacement of VAC cycles with VIT, were identified. Medical records were reviewed for clinical and disease characteristics, and treatment response and outcomes. Results Six patients were treated as per the above regimen. Median age at diagnosis was 15.1 years (range 3.2‐16.4) and five patients were male. Five patients had abdominal primary tumors, of which one had exclusively intraabdominal and four had extraabdominal metastases. Two initial cycles of VIT were well tolerated with nausea, vomiting, diarrhea, and constipation as the most common adverse events. Overall response rate defined as partial or complete response after two initial cycles of VIT was 50%. For local control, all patients had surgical resection followed by radiotherapy, and two patients received hyperthermic intraperitoneal chemotherapy at the time of surgery. Of the four patients who have completed therapy to date, three remain disease‐free with median follow‐up time of 46.7 months. Conclusions The addition of VIT to interval‐compressed chemotherapy is tolerable and active in DSRCT, with activity warranting additional investigation.

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Section: Discussionmentioning

confidence: 99%

The use of interval‐compressed chemotherapy with the addition of vincristine, irinotecan, and temozolomide for pediatric patients with newly diagnosed desmoplastic small round cell tumor

Liu

Collins

Greenzang

et al. 2020

Pediatric Blood & Cancer

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“…Second-line treatment for patients with recurrent disease that have been used are vascular endothelial growth factor (receptor) (VEGF(R))-, mammalian target of rapamycin (mTOR)-, and platelet-derived growth factor receptor (PDGFR)-based targeted therapy. These treatments can again induce favorable, however short-lived, responses (Chen and Feng 2019;Italiano et al 2013;Menegaz et al 2018;Tarek et al 2018;Thijs et al 2010). Overall, treatment results in a 5-year overall survival (OS) rate of 15-25%, which shows the high unmet need for novel treatments in DSRCTs (Bent et al 2016;Subbiah et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo

Erp¹,

Houdt²,

Hillebrandt-Roeffen³

et al. 2020

J Cancer Res Clin Oncol

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Purpose Desmoplastic small round cell tumors (DSRCTs) are highly malignant and very rare soft tissue sarcomas with a high unmet need for new therapeutic options. Therefore, we examined poly(ADP-ribose) polymerase 1 (PARP1) and Schlafen-11 (SLFN11) expression in DSRCT tumor tissue and the combination of PARP inhibitor olaparib with the alkylating agent temozolomide (TMZ) in a preclinical DSRCT model. Methods PARP1 and SLFN11 have been described as predictive biomarkers for response to PARP inhibition. Expression of PARP1 and SLFN11 was assessed in 16 and 12 DSRCT tumor tissue samples, respectively. Effects of single-agent olaparib, and olaparib and TMZ combination treatment were examined using the preclinical JN-DSRCT-1 model. In vitro, single-agent and combination treatment effects on cell viability, the cell cycle, DNA damage and apoptosis were examined. Olaparib and TMZ combination treatment was also assessed in vivo. Results PARP1 and SLFN11 expression was observed in 100% and 92% of DSRCT tumor tissues, respectively. Olaparib treatment reduced cell viability and cell migration in a dose-dependent manner in vitro. Drug synergy between olaparib and TMZ was observed in vitro and in vivo. Combination treatment led to a cell-cycle arrest and induction of DNA damage and apoptosis, even when combined at low dosages. Conclusion We show high PARP1 and SLFN11 expression in DSRCT tumor material and antitumor effects following olaparib and TMZ combination treatment in a preclinical DSRCT model. This suggests that olaparib and TMZ combination treatment could be a potential treatment option for DSRCTs.Keywords Desmoplastic small round cell tumor (DSRCT) · Poly(ADP-ribose) polymerase (PARP) · Schlafen-11 (SLFN11) · Olaparib · Temozolomide · Combination treatment Abbreviations DSRCT Desmoplastic small round cell tumor ES Ewing sarcoma PARP Poly(ADP-ribose) polymerase SLFN11 Schlafen-11 SSB Single-stranded breaks STS Soft tissue sarcoma TMZ Temozolomide Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s0043 2-020-03211 -z) contains supplementary material, which is available to authorized users.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…O erlotinibe, um inibidor multialvo da tirosina quinase, levou à resposta parcial em um relato de caso 19 . A atividade contra a doença foi relatada com uso de pazopanibe 20,21 e eribulin 22 . Relato recente demonstrou resultados negativos com imatinibe 23 bevacizumabe também foi relatada [24][25][26] .…”

Section: Discussionunclassified

Tumor Desmoplásico de Pequenas Células Redondas: Relato de Caso

Costa

Reis

Loureiro

et al. 2018

Rev. Brasileira.De.Cancerologia

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Introdução: O tumor desmoplásico de pequenas células redondas é uma rara neoplasia que se inicia e se espalha pela superfície peritoneal. Foi descrito pela primeira vez em 1989 e, em 1991, houve seu reconhecimento como entidade clínica e patológica distintas. Relato do caso: Homem de 34 anos apresentou quadro de dor abdominal e perda de peso, evoluindo para obstrução intestinal dois meses após. A laparotomia demonstrou grande massa abdominopélvica irressecável. O laudo anatomopatológico associado à imuno-histoquímica evidenciou diagnóstico de tumor desmoplásico de pequenas células redondas. A tomografia computadorizada confirmou derrame pleural bilateral, implantes peritoneais e massas abdominais e pélvicas. Realizou-se quimioterapia com carbo/taxol com intervalo de 21 dias. Substituiu-se o esquema para VAC/IE com intervalo de 21 dias, com resposta parcial, porém ainda se mantendo um tumor irressecável. Houve piora progressiva da performance do paciente, com evolução ao óbito por obstrução intestinal no 15º mês de seguimento. Conclusão: O tumor desmoplásico de pequenas células redondas, em razão da sua raridade, continua sendo um desafio para o diagnóstico e o tratamento.

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Clinical Activity of Pazopanib in Patients with Advanced Desmoplastic Small Round Cell Tumor

Cited by 39 publications

References 38 publications

The use of interval‐compressed chemotherapy with the addition of vincristine, irinotecan, and temozolomide for pediatric patients with newly diagnosed desmoplastic small round cell tumor

The use of interval‐compressed chemotherapy with the addition of vincristine, irinotecan, and temozolomide for pediatric patients with newly diagnosed desmoplastic small round cell tumor

Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo

Tumor Desmoplásico de Pequenas Células Redondas: Relato de Caso

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