Treatment of Relapsed/Refractory Pediatric Sarcomas With Gemcitabine and Docetaxel

Mora, Jaume; Cruz, Ofelia; Parareda, Andreu; Torres, Carmen de

doi:10.1097/mph.0b013e3181b2598c

Cited by 79 publications

(61 citation statements)

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“…Previous studies of recurrent and/or refractory ESFT have documented that the ORR to various salvage regimens has a range of 29-66%. The reported response rate in this study is comparable to or lower than those achieved by TC (33-35%), ICE (48%), TI (29-63%), or GD (66%) [7–10, 17, 18]. However, these regimens have been used mostly in the second- or third-line settings, whereas our DI chemotherapy was used as a ≥ fourth-line agent.…”

Section: Discussionsupporting

confidence: 50%

“…As no standard salvage regimen exists for recurrent or refractory ESFT, various regimens have been tried as second-line agents, such as topotecan plus cyclophosphamide (TC), ifosfamide, carboplatin plus etoposide (ICE), temozolomide plus irinotecan (TI), and gemcitabine plus docetaxel (GD), yielding response rates varying between 29% and 66% [7–10]. However, many patients fail to respond to these second-line agents, and chemotherapeutic options are further limited when these agents also fail.…”

Section: Introductionmentioning

confidence: 99%

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A study of docetaxel and irinotecan in children and young adults with recurrent or refractory Ewing sarcoma family of tumors

et al. 2014

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BackgroundPatients with Ewing sarcoma family of tumors (ESFT) who are resistant even to salvage chemotherapy, have dismal prognoses and few therapeutic options. Because the docetaxel/irinotecan (DI) combination has not been previously evaluated in ESFT, we prospectively evaluated its use in patients with recurrent or refractory ESFT.MethodsPatients aged <30 years with ESFT, who failed ≥ third-line therapy, were eligible. They received docetaxel 100 mg/m2 intravenously on day 1, and irinotecan 80 mg/m2 on days 1 and 8, of a 21-day cycle up to 15 cycles or until disease progressed. The primary objective was objective response rate (ORR); secondary objectives were progression-free survival (PFS) and safety.ResultsWe enrolled nine patients (median age: 13 years); four were male. Two patients had recurrent disease and seven had progressive disease. This group had undergone a median of four prior chemotherapy regimens (range: 3-6), and received a total of 51 DI cycles (median: three cycles/per person; range: 1-15 cycles). The nine patients showed one complete response (CR), two partial responses (PRs), one stable disease, and five progressive diseases, for an ORR (CR + PR) of 3/9 (33.3%). Two patients with PR achieved CR with subsequent surgery. Overall median PFS was 2.2 months (range: 0.5-16.9 months). All nine patients had grade 4 neutropenia (100%); grade 3 diarrhea or grade 2/3 neuropathy each occurred in two patients (22%). All toxicities were manageable without serious morbidities or treatment-related mortality.ConclusionsThe DI combination may be effective and tolerable for patients with heavily pre-treated ESFT.Trial registrationNCT01380275. Registered June 21, 2011.

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Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

A study of docetaxel and irinotecan in children and young adults with recurrent or refractory Ewing sarcoma family of tumors

et al. 2014

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“…Since 2006, all metastatic patients received 1 year of maintenance chemotherapy according to the institutional regimen with gemcitabine and docetaxel, as previously reported [14].…”

Section: Metastatic Diseasementioning

confidence: 99%

Treatment of Ewing sarcoma family of tumors with a modified P6 protocol in children and adolescents

Mora

Torres

Parareda

et al. 2011

Pediatric Blood & Cancer

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INTRODUCTIONEwing sarcoma family of tumors (ESFT) is the second most common bone malignancy in children, accounting for approximately 40% of all bone cancers [1]. ESFT is characterized by a specific balanced chromosomal translocation which fuses the amino-terminal domain of the EWSR1 gene or, in rare cases, the TLS/FUS gene, to the DNA-binding domain of one of five ETS genes [2]. The transcripts resulting from these fusion genes can be detected using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. RT-PCR provides a higher sensitivity than conventional cytological analysis to detect tumor cells in bone marrow (BM) and peripheral blood (PB). Previous studies have reported that among patients with local-regional ESFT, RT-PCR positivity of BM correlates with a high risk of adverse outcome and significantly poorer disease-free survival rates [3]. Thus, RT-PCR analysis of BM might be useful to classify localized and metastatic patients at diagnosis.Treatment of ESFT has improved over the last two decades with reported durable remissions in 50-70% of non-metastatic patients [4]. In 1995, the group at MSKCC published the P6 protocol showing a successful induction of remission in patients with localregional disease and good initial responses with dose-intensive and short-term chemotherapy in patients with distant metastases [5]. A subsequent and extended outcome data on 68 patients (44 localized) with ESFT treated with the P6 protocol showed a 4-year EFS and OS for patients with localized disease of 82% and 89%, respectively. Patients with detectable metastatic disease at diagnosis had a significantly worse prognosis, with a 4-year EFS rate of 12% and OS rate of 17.8% [6].In 1998, the MSKCC group reported a cumulative incidence of therapy related acute myelogenous leukemias (t-AML) and myelodysplastic syndromes (MDS) at 40 months of 8% in survivors of the P6 protocol [7]. The latest report from the MSKCC group [6] details three patients experiencing secondary MDS/t-AML out of 44 non-metastatic patients, which makes a 7% incidence in the population with longest overall survival. This and other experiences suggested that repetitive use of high-dose alkylating agents given with topoisomerase-II inhibitors is strongly leukemogenic, even with modest cumulative doses of each drug. The two well-described kinds of t-AML/MDS occurred, namely, those associated with topoisomerase-II inhibitors and marked by early emergence of t-AML with translocations of the MLL gene at chromosome band 11q23, and those associated with alkylating agents and marked by an MDS, whole or partial deletions of chromosomes 5 or 7, and a latency period of 2-8 years [8,9].In 2001, we modified the original P6 (hereby mP6) protocol by: (1) reducing the number of chemotherapy cycles down to five, three CDV and two IE, in order to decrease the risk of secondary tumors; (2) using higher doses of ifosfamide (2.8 g/m 2 /day instead of 1.8 g) post-surgery in cases with poor histological response; and (3) using dexrazoxane before doxorubicin t...

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“…Using RECIST, objective complete responses were observed in four patients (40%), partial response in one, and stable disease in three (30%), for an overall objective response rate of 50%. The median duration of response was 10 months (range 6-32þ months), and there were no grade 3 or 4 toxicities reported [30 ].…”

Section: Clinical Activity Of Fixed-dose-rate Gemcitabine and Docetaxmentioning

confidence: 94%

Update on gemcitabine and docetaxel combination therapy for primary and metastatic sarcomas

Hensley

2010

Current Opinion in Oncology

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Treatment of Relapsed/Refractory Pediatric Sarcomas With Gemcitabine and Docetaxel

Abstract: The gemcitabine-docetaxel regimen demonstrated antitumor activity against advanced pediatric (mainly Ewing) sarcomas, allowing for good quality of life. Evaluation in a large, formal phase 2 trials for Ewing patients is ongoing.

Cited by 79 publications

References 19 publications

A study of docetaxel and irinotecan in children and young adults with recurrent or refractory Ewing sarcoma family of tumors

A study of docetaxel and irinotecan in children and young adults with recurrent or refractory Ewing sarcoma family of tumors

Treatment of Ewing sarcoma family of tumors with a modified P6 protocol in children and adolescents

Update on gemcitabine and docetaxel combination therapy for primary and metastatic sarcomas

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