High histologic and overall response to dose intensification of ifosfamide, carboplatin, and etoposide with cyclophosphamide, doxorubicin, and vincristine in patients with high‐risk ewing sarcoma family tumors

Milano, Giuseppe Maria; Cozza, Raffaele; Ilari, Ilaria; Sio, Luigi De; Boldrini, Renata; Jenkner, Alessandro; Ioris, Maria Antonietta De; Inserra, Alessandro; Dominici, Carlo; Donfrancesco, Alberto

doi:10.1002/cncr.21780

Cited by 25 publications

(25 citation statements)

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“…Ewing sarcoma family tumors are extremely aggressive tumors, predominantly occurring in children and young adults, but can develop at any age. In the past decades, ESFT outcome was improved through a multidisciplinary strategy based on surgery, radiotherapy, and, in selected cases, intensified chemotherapy, whereas the risk factors associated with the prognosis were clearly identified in large series of patients [1,2]. More than 90% ESFT express at very high level an antigen determined by the MIC2 gene [2,3], whose product is a glycoprotein also designated CD99 or p30/32, which is a reliable marker for ESFT.…”

Section: Discussionmentioning

confidence: 98%

“…The patient is alive and well with no evidence of disease at 54 months of age without any impairment secondary to treatment. According to our previous experience [1], the ICE-CAV regimen that was administered with the chemotherapy dose adjusted for weight was well tolerated with manageable short-and long-term toxicities.…”

Section: Discussionmentioning

confidence: 99%

“…The child underwent chemotherapy following ICE (ifosfamide, carboplatin, etoposide)-CAV (cyclophosphamide, doxorubicin, vincristine) protocol [1] adjusted for age and weight considering a square meter equivalent to 30 kg and a further dose reduction (25%-30%) for a weight less than 5 kg. The chemotherapy was well tolerated; the main toxicity was hematologic with grade 3/4 neutropenia and/or thrombocytopenia according to the Common Terminology Criteria for Adverse Events Version 4, whereas extrahematologic toxicities grade 2/4 were not reported.…”

Section: Case Reportmentioning

confidence: 99%

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Congenital Askin tumor with favorable outcome: case report and review of the literature

Crocoli

Bagolan

Boldrini

et al. 2012

Journal of Pediatric Surgery

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 99%

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Congenital Askin tumor with favorable outcome: case report and review of the literature

Crocoli

Bagolan

Boldrini

et al. 2012

Journal of Pediatric Surgery

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“…[11][12][13][14] Platinum compounds have been used as first-line therapy in patients with ES, in a very limited number of studies, mostly in combination with other drugs, generally administered at doses of 70 to 100 mg/m 2 , and some authors reported its effectiveness in the preoperative treatment of ES. [15][16][17] In this patient the local treatment on the site of the primary consisted of RT alone. We are aware that a factor influencing the outcome in ES is surgery, which gives better results than RT alone in a nonlocalized ES setting, but surgery was not possible because his mother refused a demolitive surgical approach-arm amputation-because of religious reasons.…”

Section: Discussionmentioning

confidence: 99%

Dramatic Response to Cisplatin Window Therapy in a Boy With Advanced Metastatic Ewing Sarcoma

Trizzino

Ziino²,

Parafioriti

et al. 2013

Journal of Pediatric Hematology/Oncology

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Summary: Ewing sarcoma (ES) is the second most common type of primary bone malignancy, and retains a high propensity to metastasize; the prognosis of patients with disseminated disease is very poor, with an event-free survival rate of <20%. Current multimodality treatment for ES consists of combined chemotherapy before and concurrent with surgery and local radiotherapy for the involved bone. Cisplatin is one of the most widely used drugs for the treatment of bone tumors in children, but is not currently used in ES. We describe a child with multifocal ES, treated with a phase II trial including a single-drug window therapy, which displayed a dramatic response to 2 courses of cisplatin and had a favorable outcome.Key Words: Ewing sarcoma, advanced metastatic disease, window therapy, cisplatin, outcome (J Pediatr Hematol Oncol 2013;35:478-481) E wing sarcoma (ES) is the second most common bone malignancy in children and young adults, with a slight male predominance. 1 ES has a high propensity to metastasize, and about 25% of patients show disseminated involvement at the beginning of disease. Multimodal treatment approaches, including surgery, radiotherapy (RT), and intensive multidrug chemotherapy, have led to notable improvement in the outcome of patients with localized disease, up to about 70% of event-free survival (EFS). 2,3 In contrast, the prognosis of patients with primary disseminated disease remains very poor, with an EFS of <20%. 4 Patients with primary pulmonary metastases show a better outcome than patients with primary bone and/or bone marrow involvement. 4-8 Conventional treatment regimens for localized ES generally consist of a combination of vincristine, actinomycin-D, cyclophosphamide, doxorubicin, ifosfamide, and etoposide. Adjunctive surgical resection with or without radiation therapy is used for local control. Most episodes of disease recurrence occur after completion of therapy, and most recurrences (approximately 80%) occur within 2 years from initial diagnosis. 9 Cisplatin (CDDP) and other platinum compounds are widely used drugs for the treatment of solid tumors in adults and children, especially when failure of first-line therapy occurs, but data concerning its activity and efficacy are very limited in ES.We describe an impressive response to front-line CDDP as a single drug in a child with metastatic ES with a favorable clinical outcome. CASE REPORTA 10-year-old African boy was admitted 10 months after the onset of left elbow pain, followed by progressive swelling. He was diagnosed with an osteosarcoma (small cell variant) of the left arm in a Nigerian Hospital. He did not receive any therapy in Nigeria because they concentrate the few economical resources available on patients with more chances of healing. An international committee organized a transfer abroad to verify the histologic diagnosis and to explore the possibility of a therapeutic approach.On admission the boy showed a huge mass (circumference 43 cm, whereas the contralateral was 15 cm) in the left elbow, and packed lymph n...

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“…Induction chemotherapy was based on two ifosfamide/ carboplatin/etoposide courses and two CY/doxorubicin/ VCR, as previously reported, 13 and two CY/etoposide courses and a subsequent CY/doxorubicin/VCR course (see Figure 1). Surgery was considered at diagnosis and after the fourth course.…”

Section: Treatment Planmentioning

confidence: 99%

Toxicity of high-dose chemotherapy with etoposide, thiotepa and CY in treating poor-prognosis Ewing's sarcoma family tumors: the experience of the Bambino Gesù Children's Hospital

Ilari

Ioris

Milano³

et al. 2010

Bone Marrow Transplant

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We report the toxicity of high-dose chemotherapy (HDC) based on etoposide, thiotepa and CY (ETC) in children with poor-prognosis Ewing's sarcoma family tumors (ESFTs). A total of 26 patients with high-risk ESFT (metastasis or axis localization or tumor volume 4200 ml or necrosis o95%) were reviewed. The conditioning was based on etoposide (600 mg/m 2 ), thiotepa (750 mg/m 2 ) and CY (120 mg/kg) followed by autologous BM or PBSC rescue. The conditioning regimen was well tolerated, without any toxic deaths. The median time from transplant to a neutrophil count of 40.5 Â 10 9 /l was 10 days (range 6-27) and 22.5 days (range 9-114) for a plt count of 450 Â 10 9 /l. Oral mucositis was recorded in 20 patients, grade 1/2 in 19 and grade 3 in the last patient. Diarrhea grade 1/2 was recorded in four patients and grade 1/2 liver toxicity in four patients. Sepsis was documented in four cases and skin toxicity in three. Lung and tubular toxicity, respectively, were reported in one patient each. We conclude that the ETC regimen presented a limited and manageable toxicity. Further studies would confirm the role of ETC in high-risk ESFT.

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High histologic and overall response to dose intensification of ifosfamide, carboplatin, and etoposide with cyclophosphamide, doxorubicin, and vincristine in patients with high‐risk ewing sarcoma family tumors

Abstract: The authors thank M. Mercuri, M.D., and M. Manfrini, M.D. (Istituti Orthopedici Rizzoli, Bologna, Italy, for performing surgery on patients with skeletal involvement.

Cited by 25 publications

References 35 publications

Congenital Askin tumor with favorable outcome: case report and review of the literature

Congenital Askin tumor with favorable outcome: case report and review of the literature

Dramatic Response to Cisplatin Window Therapy in a Boy With Advanced Metastatic Ewing Sarcoma

Toxicity of high-dose chemotherapy with etoposide, thiotepa and CY in treating poor-prognosis Ewing's sarcoma family tumors: the experience of the Bambino Gesù Children's Hospital

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