Phase II study of vinorelbine and continuous low doses cyclophosphamide in children and young adults with a relapsed or refractory malignant solid tumour: Good tolerance profile and efficacy in rhabdomyosarcoma – A report from the Société Française des Cancers et leucémies de l’Enfant et de l’adolescent (SFCE)

Minard‐Colin, Véronique; Ichante, Jean-Laurent; Nguyen, Laurent; Paci, Angélo; Orbach, Daniel; Bergeron, Christophe; Defachelles, Anne‐Sophie; André, Nicolas; Corradini, Nadège; Schmitt, Claudine; Tabone, Marie‐Dominique; Blouin, P.; Sirvent, Nicolas; Goma, G.; Geoerger, Birgit; Oberlin, Odile

doi:10.1016/j.ejca.2012.04.012

Cited by 57 publications

(70 citation statements)

References 34 publications

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“…[24][25][26]28 The underlying disease must have been relapsed after or refractory to conventional therapy and/or for which no effective treatment was available. Four studies included newly diagnosed patients with malignant supratentorial or pontine gliomas.…”

Section: Description Of the Phase I And Ii Trialsmentioning

confidence: 99%

Patients in Pediatric Phase I and Early Phase II Clinical Oncology Trials at Gustave Roussy

Bautista

Giannatale²,

Dias-Gastellier³

et al. 2015

Journal of Pediatric Hematology/Oncology

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In the European Union, the pediatric medicines regulation in 2007 modified significantly the access to new agents in pediatric oncology. Early oncology trials are still thought to be associated with limited benefit and substantial risk. We report the characteristics and outcome of patients below 21 years enrolled in investigational trials in the Pediatric and Adolescent Department at Gustave Roussy between January 2000 and December 2012. A total of 235 patients (median age, 10.4 [0.8 to 20.7] y) were included in 26 trials (16 cytotoxic and 10 targeted agents) for a total of 260 inclusions. A total of 117 patients (50%) had brain tumors and 68 (29%) had various soft tissue and bone sarcoma. Thirteen of the 106 patients in a phase I trial experienced dose-limiting toxicity. Main severe toxicity was hematologic; none had toxic death. Grade 3 to 4 toxicities were associated with combination trials, cytotoxic agent, and at least 1 previous line of therapy. Thirty patients (12%) had objective response and 42 (16%) had stable disease for >4 months. Median overall survival was 9.0 months (95% CI, 7.5-10.5) and 73% of patients received further anticancer treatment. Phase I to II pediatric oncology trials are safe, associated with clinical benefit, and can be successfully integrated in current relapse strategies.

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Section: Description Of the Phase I And Ii Trialsmentioning

confidence: 99%

Patients in Pediatric Phase I and Early Phase II Clinical Oncology Trials at Gustave Roussy

Bautista

Giannatale²,

Dias-Gastellier³

et al. 2015

Journal of Pediatric Hematology/Oncology

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“…Enrollment on a clinical trial is preferable for patients with relapsed RMS. For those not on a therapeutic study, multiple salvage chemotherapy regimens with documented activity may be considered (Table ) . There has been no direct comparison of these therapies to identify one optimal treatment, so therapy decisions are often impacted by the extent and type of prior treatment, as well as patient condition and enthusiasm for further therapy.…”

Section: Questionsmentioning

confidence: 99%

Consensus and controversies regarding the treatment of rhabdomyosarcoma

Borinstein

Steppan

Hayashi

et al. 2017

Pediatric Blood & Cancer

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Optimal treatment of rhabdomyosarcoma (RMS) requires multidisciplinary approach, incorporating chemotherapy with local control. Although current therapies are built on cooperative group trials, a comprehensive standard of care to guide clinical decision making has been lacking, especially for relapsed patients. Therefore, we assembled a panel of pediatric and adolescent and young adult sarcoma experts to develop treatment guidelines for managing RMS and to identify areas in which further research is needed. We created algorithms incorporating evidence-based care for patients with RMS, emphasizing the importance of clinical trials and close integration of all specialties involved in the care of these patients.

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“…More recently, in a Phase II study performed by the Société Française des Cancers et leucémies de l'Enfant et de l'adolescent, efficacy of the vinorelbine plus cyclophosphamide combination was assessed in children and young adults with recurrent or refractory solid tumors [29]. This protocol recruited also ten HGOS patients, who unfortunately did not respond to this treatment approach.…”

Section: Vinca Alkaloids (Vinorelbine Vinblastine)mentioning

confidence: 99%

“…Vincristine + methotrexate + doxorubicin [27] Vincristine + high-dose methotrexate + cisplatin [28] Vinorelbine + cyclophosphamide [29] Paclitaxel (used as single drug) [32] Docetaxel + gemcitabine [38,44,45] Etoposide + high-dose methotrexate + ifosfamide [47] Etoposide + high-dose methotrexate + doxorubicin + cisplatin + ifosfamide [50,51] Etoposide + ifosfamide [53] Etoposide + cyclophosphamide [75] Etoposide + high-dose ifosfamide [54] Etoposide + carboplatin [80] Etoposide + ifosfamide + doxorubicin + methotrexate [55] Bleomycin + doxorubicin + cisplatin + methotrexate + dactinomycin + cyclophosphamide [60][61][62][63][64] Bleomycin (used as single drug) with electroporation [65] Carboplatin (used as single drug) [78,79] Carboplatin + ifosfamide + etoposide [81] Carboplatin + high-dose methotrexate + doxorubicin + ifosfamide [82] Carboplatin + doxorubicin + cyclophosphamide + etoposide [83] Topotecan (used as single drug) [88,89] Topotecan + cyclophosphamide [90][91][92] Topotecan + ifosfamide + carboplatin + etoposide, alternating with cisplatin and doxorubicin [93] Irinotecan (used as single drug) [94,95] Irinotecan + gemcitabine [96] Irinotecan + gefitinib (EGF inhibitor) [97] Irinotecan + temsirolimus (mTOR inhibitor) + temozolomide [98] Second-line drugs are in bold.…”

Section: Drug Combinationmentioning

confidence: 99%

Pharmacogenomics of Second-Line Drugs Used for Treatment of Unresponsive or Relapsed Osteosarcoma Patients

Hattinger¹,

Vella²,

Tavanti³

et al. 2016

Pharmacogenomics

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Second-line treatment of high-grade osteosarcoma (HGOS) patients is based on different approaches and chemotherapy protocols, which are not yet standardized. Although several drugs have been used in HGOS second-line protocols, none of them has provided fully satisfactory results and the role of rescue chemotherapy is not well defined yet. This article focuses on the drugs that have most frequently been used for second-line treatment of HGOS, highlighting the present knowledge on their mechanisms of action and resistance and on gene polymorphisms with possible impact on treatment sensitivity or toxicity. In the near future, validation of the so far identified candidate genetic biomarkers may constitute the basis for tailoring treatment by taking the patients' genetic background into account. Osteosarcoma is the most common tumor of bone, which can exibit different levels of malignancy [1,2]. High-grade osteo sarcoma (HGOS) is a very aggressive neoplasm that, in unselected populations, is responsible for death of approximately 40-50% of patients [2,3]. The subgroup of the so-called conventional HGOS includes patients with high-grade tumors located in the extremities, nonmetastatic at diagnosis and younger than 40 years [1]. In this subgroup of HGOS, prognosis is slightly better, reaching 60-65% when patients are treated with multiagent neoadjuvant chemotherapy [4][5][6].The major clinical problem limiting the cure rate of HGOS patients is relapse, which in most cases consists in development of lung metastasis within the first 24-36 months from diagnosis [7,8]. Treatment of relapsed HGOS is based on different approaches and second-line chemotherapy protocols which, however, are not standardized and can rescue no more than 20-25% of patients [4,5]. Methods of data searching & selectionA systematic literature search was performed using 'treatment' and 'osteosarcoma' as key words in PubMed [9]. We further restricted the selection to studies performed in humans. By using all the aforementioned different combinations and selections, the literature searches revealed a total of 13,976 results. The key terms 'polymorphism', 'toxicity', 'drug response', 'drug resistance', 'pharmaco genetic', 'pharmacogenomic', 'epigenetic', 'methylation' and 'clinical trial' were then used to refine the results of the previous search, in order to select the publications which were strictly related to each section of this review. Full-length articles and reviews in English were taken into consideration.Only drugs used in at least two different clinical trials with published results were included in this review and, consequently, we considered genes and gene poly morphisms with possible relevance for response and/or

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Cited by 57 publications

References 34 publications

Patients in Pediatric Phase I and Early Phase II Clinical Oncology Trials at Gustave Roussy

Patients in Pediatric Phase I and Early Phase II Clinical Oncology Trials at Gustave Roussy

Consensus and controversies regarding the treatment of rhabdomyosarcoma

Pharmacogenomics of Second-Line Drugs Used for Treatment of Unresponsive or Relapsed Osteosarcoma Patients

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