No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

Massimino, Maura; Gandola, Lorenza; Spreafico, Filippo; Biassoni, Veronica; Luksch, Roberto; Collini, Paola; Solero, Carlo; Simonetti, Fabio; Pignoli, E.; Cefalo, Graziella; Poggi, Geraldina; Modena, Piergiorgio; Mariani, Luigi; Potepan, Paolo; Podda, Marta; Casanova, Michela; Pecori, Emilia; Acerno, Stefania; Ferrari, Andrea; Terenziani, Monica; Meazza, Cristina; Polastri, Daniela; Ravagnani, Fernando; Fossati-Bellani, Franca

doi:10.1016/j.ijrobp.2008.06.1930

Cited by 49 publications

(35 citation statements)

References 24 publications

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“…But the HDC patients of this trial had chemo-responsive disease. Nevertheless, the result of this and another multicenter study [22] gives evidence that augmentation of chemotherapy is of no general benefit for relapsed patients with cerebral PNETs [25][26][27]. Whether intensification of chemotherapy may benefit individual patients, cannot be excluded.…”

Section: Discussionmentioning

confidence: 86%

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Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial

et al. 2014

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Early studies with high-dose chemotherapy for treatment of relapsed cerebral PNET had shown modest efficacy but considerable toxicity. The HIT97 national trial tested a nonrandomized but stratified relapse protocol using either intensive chemotherapy, potentially high dose, or oral chemotherapy. 72 patients (59 disseminated) whose primary treatment had been surgery (97 %), radiotherapy (88 %), and/or chemotherapy (95 %) were enrolled in the intensive chemotherapy arm at diagnosis of relapse or resistance. As a window for this study they received two courses of a 96-hour infusion with carboplatin and etoposide. A response (complete or partial remission) was documented by MRI. Responders received two more cycles of this therapy and stem cell collection, before they received HDC (carboplatin, etoposide, thiotepa) and stem cell support. All possibilities of local therapy were to be explored and applied. After two courses of chemotherapy there was a 52 % response rate (41/72 patients). The median PFS and OS for all 72 patients were 11.6 and 21.1 months. Patients with medulloblastoma had a longer PFS and OS (12.6 and 22.6 months) than those with other PNETs (3.1 and 12.3 months). Favourable prognostic features were no new signs of clinical impairment and localised disease at relapse diagnosis. For the 27 patients who received HDC the median PFS and OS were 8.4 and 20.2 months, respectively. HDC did not benefit patients with resistant cerebral PNET and was associated with profound haematological and mucosal toxicity (90-100 % grade III, IV), infections (50 % grade III and IV) and severe ototoxicity (50 % grade III, 12.5 % grade IV). Treatment related mortality was 8 %. There was low long-term survival and only 2/72 patients are in continuous remission. Adding HDC in patients who responded to the initial courses of chemotherapy did not improve survival. Patients with relapsed cerebral PNET who respond to conventional chemotherapy do not profit from further augmentation to HDC.

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Section: Discussionmentioning

confidence: 86%

“…Mostly the patients who survive have the surgical or radiotherapeutic option still available [21][22][23]25]. Therefore the role of intensive chemotherapy is difficult to evaluate in these patients.…”

Section: Discussionmentioning

confidence: 99%

Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial

et al. 2014

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“…Standardized relapse protocols are few. Many treatment modalities, even high-dose chemotherapy with stem cell rescue, have been used, without any prognostic breakthrough [6][7][8].…”

Section: Discussionmentioning

confidence: 99%

Treatment for recurrent medulloblastoma with intrathecal liposomal cytarabine and systemic metronomic combination therapy

Nygaard

Kivivuori²

2012

Anti-Cancer Drugs

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The prognosis of recurrent medulloblastoma is dismal, with a median survival of less than 1 year. Our patient was initially diagnosed with high-risk medulloblastoma when he was 14 years old. He had a recurrence 18 months after the end of therapy. Recurrence treatment consisted of 13 intrathecal applications of liposomal cytarabine over an 18-month period, and oral metronomic antiangiogenic therapy with thalidomide, celecoxib, and etoposide. Side effects from the intrathecal treatment were most likely related to arachnoiditis despite prolonged prophylaxis with steroids. He also developed partial hearing loss. Neutropenia was the main side effect of the metronomic therapy. He remains alive, with a good quality of life and without evidence of disease 34 months from the start of recurrence therapy. This combination of local antineoplastic and systemic antiangiogenic therapy seems to be promising for recurrent medulloblastoma. However, more patients and standardized protocols are needed to verify the benefit of this combination therapy and to define the correct duration of treatment.

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“…For disease recurrent after RT with or without CT, numerous studies demonstrate chemo responsiveness to single agents, multiagent combinations, and high-dose therapy with hematologic stem cell rescue. Except in the infant setting, durable secondary disease control following initial CSI has only rarely been achieved despite aggressive, high-dose CT and further irradiation (129,130,131). Local irradiation can provide further control at the primary site (132).…”

Section: Chemotherapymentioning

confidence: 99%

Malignant Brain Tumors in Childhood

Scarzello

Buzzaccarini

Sotti

2011

Management of CNS Tumors

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No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

Cited by 49 publications

References 24 publications

Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial

Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial

Treatment for recurrent medulloblastoma with intrathecal liposomal cytarabine and systemic metronomic combination therapy

Malignant Brain Tumors in Childhood

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