Phase II Study of Weekly Vinblastine in Recurrent or Refractory Pediatric Low-Grade Glioma

Bouffet, Éric; Jakacki, Regina I.; Goldman, Stewart; Hargrave, Darren; Hawkins, Cynthia; Shroff, Manohar; Hukin, Juliette; Bartels, Ute; Foreman, Nicholas K.; Kellie, Stewart J.; Hilden, Joanne M.; Etzl, Michael; Wilson, Beverly; Stephens, Derek; Tabori, Uri; Baruchel, Sylvain

doi:10.1200/jco.2011.34.5843

Cited by 202 publications

(135 citation statements)

References 29 publications

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“…7,[32][33][34][35][36] Indeed, many of these patients experience multiple tumor progressions, and upfront aggressive treatment options such as radiation therapy are being used to avoid potential patient demise. Despite multiple progressions, we observed >90% survival 20 to 25 years after the diagnosis in the absence of aggressive modalities such as radiotherapy and no late mortality due to tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Clinical and treatment factors determining long‐term outcomes for adult survivors of childhood low‐grade glioma: A population‐based study

Krishnatry

Zhukova

Stücklin

et al. 2016

Cancer

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124

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BACKGROUND:The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown. METH-ODS: This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n 5 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database. RESULTS: At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% 6 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P <.001) and a thalamic location (P <.001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6-6.6; P 5.001) and an approximately 4-fold increased risk of tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P 5.013). In a multivariate analysis, radiotherapy was the most significant factor associated with late all-cause deaths (HR, 3.0; 95% CI, 1.3-7.0; P 5.012) and tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P 5 0.014). A similar association between radiotherapy and late deaths was observed in the independent reference cohort (P <.001). In contrast to early deaths, late mortality was associated not with PLGG progression but rather with tumor transformation and non-oncological causes. CONCLUSIONS: The course of PLGG is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients. Cancer 2016;122:1261-9.

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Section: Discussionmentioning

confidence: 99%

Clinical and treatment factors determining long‐term outcomes for adult survivors of childhood low‐grade glioma: A population‐based study

Krishnatry

Zhukova

Stücklin

et al. 2016

Cancer

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124

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“…Antitumour treatment included surgery, chemotherapy, radiotherapy and a combination of these, according to national or international protocols [25,26,27,28] (table 2). Surgery consisted of complete or partial tumour resection.…”

Section: Methodsmentioning

confidence: 99%

Water and Electrolyte Disorders at Long-Term Post-Treatment Follow-Up in Paediatric Patients with Suprasellar Tumours Include Unexpected Persistent Cerebral Salt-Wasting Syndrome

Briceño¹,

Grill

Bourdeaut

et al. 2014

Horm Res Paediatr

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Background: Patients with brain tumours have a high risk of water and electrolyte disorders (WED). Postsurgery diabetes insipidus (DI) may be transient or permanent, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt-wasting syndrome (CSWS) are usually transient. Methods: Retrospective study, including patients with suprasellar tumours, treated at Hôpital Necker, Institut Gustave-Roussy or Institut Curie, in Île-de-France, between 2007 and 2011. WED were noted if they persisted >1 month after surgery. Results: 159 patients were included, 54.1% girls, 43.9% boys. Tumour types were: glioma (43.4%), craniopharyngioma (43.4%), germinoma (11.3%), others (1.9%). Age at diagnosis was 7.1 ± 4.6 years. The median time from end of treatment was 1.9 (0-7.8) years. DI was the most frequent disorder after tumour treatment (50.3%) and was significantly associated with surgery (p < 0.001). Persistent CSWS was present in 3.6%, persistent SIADH in 1.3%. Two cases of hypernatraemia were due to adipsia. Thyrotropin deficiency after treatment was noted in 68.9% of patients tested, adrenocorticotropin deficiency in 66.2%. Conclusions: Patients with suprasellar tumours have a high incidence of long-term WED, mainly DI. Assessment of thyrotroph and corticotroph function, and thirst sensation, is necessary to diagnose and manage these disorders correctly. CSWS may be persistent in few patients and requires special attention to prescribe the appropriate care.

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“…Although vinblastine is a lipophilic agent, animal studies showed low brain penetration and a low concentration in brain tissue and cerebrospinal fluid. One explanation for the activity of vinblastine in gliomas could be in its antiangiogenic activity through endothelium-directed toxicity 6,12 , a concept that is supported by preclinical data showing antiangiogenic activity with low-dose vinblastine 14,15 .…”

Section: Discussionmentioning

confidence: 91%

“…A phase ii study of weekly vinblastine in recurrent low-grade glioma demonstrated very good results, with an excellent toxicity profile in comparison with alternative strategies 6 . It might even be speculated that low-dose vinblastine was not only acting as an antiangiogenic agent, but might also have activated dendritic cells 16 .…”

Section: Discussionmentioning

confidence: 99%

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Successful Use of Metronomic Vinblastine and Fluorothymidine pet Imaging for the Management of Intramedullary Spinal Cord Anaplastic Oligoastrocytoma in a Child

et al. 2014

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Exploration of new therapeutic options and management strategies is an ongoing need. CASE DESCRIPTIONAn 11-year-old girl had a history of progressive low back pain, incontinence, and paraparesis of both lower extremities lasting 4 months before her diagnosis with an intramedullary spinal cord tumour at the T9-10 level. Sensory irritative paresthesia with prurigo and perception changes led to intensive scratching and a bacterial superinfection resembling scabies. Histopathology revealed an anaplastic oligoastrocytoma, World Health Organization grade 3 as assessed by two board-certified pathologists.Subsequent follow-up with array-based comparative genomic hybridization studies revealed a total loss of 1p and 19q. Magnetic resonance imaging (mri) showed tumour involvement of the whole diameter of spine without any signs of metastatic disease, but complete resection was deemed impossible by several neurosurgeons.Treatment was commenced according to the ACNS0126 protocol with temozolomide (90 mg/m 2 ) for 42 days with concomitant radiotherapy (45 Gy) to the tumour bed 3 . Because of grade 4 myelosuppression lasting 5 weeks and the reappearance of clinical symptoms, that treatment protocol was stopped. The patient was then offered low-dose combat metronomic chemotherapy (temozolomide, etoposide, celecoxib, retinoic acid) 4 , which contained combat ii (plus vitamin D and fenofibrate) and combat iii 5 (plus bevacizumab) for 31 months, using temozolomide 30 mg/m 2 daily for 42 days and etoposide 25 mg/m 2 daily. However, that dosing schedule had to be reduced by 50% because of grades 3 and 4 bone marrow toxicity. Tumour assessment by mri after 30 months of metronomic treatment revealed stable disease, with very high avidity on both 18 F-f luorodeoxyglucose (fdg) positron-emission tomography (pet) and 18 Ffluorothymidine (flt) pet (Figure 1). ABSTRACT BackgroundChildren with high-grade glioma still have a poor prognosis despite the use of multimodal therapy including surgery, radiotherapy, and chemotherapy. New therapeutic strategies and methods evaluating such therapies are needed. ObservationHere we describe a child with anaplastic oligodendroglioma of the spinal cord who was unable to tolerate standard chemoradiotherapy and who had still-vital residual tumour during therapy. A good response was obtained with low-dose metronomic treatment containing vinblastine. The treatment was guided according to gradual response assessed using various positron-emission tomography tracers. ConclusionsMetronomic treatment guided by positron-emission tomography could be a reasonable option in some high-risk pediatric tumours.

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Phase II Study of Weekly Vinblastine in Recurrent or Refractory Pediatric Low-Grade Glioma

Cited by 202 publications

References 29 publications

Clinical and treatment factors determining long‐term outcomes for adult survivors of childhood low‐grade glioma: A population‐based study

Clinical and treatment factors determining long‐term outcomes for adult survivors of childhood low‐grade glioma: A population‐based study

Water and Electrolyte Disorders at Long-Term Post-Treatment Follow-Up in Paediatric Patients with Suprasellar Tumours Include Unexpected Persistent Cerebral Salt-Wasting Syndrome

Successful Use of Metronomic Vinblastine and Fluorothymidine pet Imaging for the Management of Intramedullary Spinal Cord Anaplastic Oligoastrocytoma in a Child

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