Prospective study of carmustine wafers in combination with 6-month metronomic temozolomide and radiation therapy in newly diagnosed glioblastoma: Preliminary results

Andrea Salmaggi, Ida Milanesi, Antonio Silvani, Paola Gaviani, Marcello Marchetti, Laura Fariselli, Carlo Lazzaro Solero, Carmelo Maccagnano, Cecilia Casali, Sara Guzzetti, Bianca Pollo, Emilio Ciusani, Francesco DiMeco

Research output: Contribution to journalArticle

Abstract

Object. Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemo-therapy with temozolomide. A combination of carmustine wafers with the Stupp treatment regimen has only been investigated in retrospective studies. Methods. In a single-institution prospective study, the authors assessed 12-month progression-free survival (PFS), toxicity, and overall survival in patients with glioblastoma treated with surgery, carmustine wafers, radiotherapy, and 6-month metronomic temozolomide chemotherapy. Thirty-five patients with de novo glioblastoma, between the ages of 18 and 70 years, and with Karnofsky Performance Scale scores of at least 70, were included in the study. Patients were followed monthly and assessed using MRI every 2 months. Results. After a median follow-up of 15 months, the median time to tumor progression was 12.5 months and median survival was 17.8 months. Due to toxicity (mostly hematological), 7 patients had to prematurely stop temozolomide treatment. Twenty-two patients developed Grade 3 CD4+ lymphocytopenia. Three patients developed oral-esophageal candidiasis, 2 developed pneumonia, and 1 developed a dorsolumbar zoster. Early intracranial hypertension was observed in 1 patient, and 1 was treated empirically for suspected brain abscess. One patient died of Legionella pneumonia soon after repeat surgery. Conclusions. Overall, this treatment schedule produced promising results in terms of PFS without a marked increase in toxicities as compared with the Stupp regimen. However, the gain in median survival using this schedule was less clear. Only prospective comparative trials will determine whether these preliminary results will translate into a long-term survival advantage with an acceptable toxicity profile.

Original languageEnglish (US)
Pages (from-to)821-829
Number of pages9
JournalJournal of Neurosurgery
Volume118
Issue number4
DOIs
StatePublished - Apr 2013
Externally publishedYes

Fingerprint

temozolomide
Carmustine
Glioblastoma
Radiotherapy
Prospective Studies
Survival
Disease-Free Survival
Pneumonia
Appointments and Schedules
Oral Candidiasis
Karnofsky Performance Status
Drug Therapy
Legionella
Brain Abscess
Lymphopenia
Intracranial Hypertension
Herpes Zoster
Therapeutics

Keywords

  • Gliadel
  • Glioblastoma
  • Metronomic
  • Oncology
  • Radiation therapy
  • Temozolomide

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Prospective study of carmustine wafers in combination with 6-month metronomic temozolomide and radiation therapy in newly diagnosed glioblastoma : Preliminary results. / Salmaggi, Andrea; Milanesi, Ida; Silvani, Antonio; Gaviani, Paola; Marchetti, Marcello; Fariselli, Laura; Solero, Carlo Lazzaro; Maccagnano, Carmelo; Casali, Cecilia; Guzzetti, Sara; Pollo, Bianca; Ciusani, Emilio; DiMeco, Francesco.

In: Journal of Neurosurgery, Vol. 118, No. 4, 04.2013, p. 821-829.

Research output: Contribution to journalArticle

Salmaggi, A, Milanesi, I, Silvani, A, Gaviani, P, Marchetti, M, Fariselli, L, Solero, CL, Maccagnano, C, Casali, C, Guzzetti, S, Pollo, B, Ciusani, E & DiMeco, F 2013, 'Prospective study of carmustine wafers in combination with 6-month metronomic temozolomide and radiation therapy in newly diagnosed glioblastoma: Preliminary results', Journal of Neurosurgery, vol. 118, no. 4, pp. 821-829. https://doi.org/10.3171/2012.12.JNS111893
Salmaggi, Andrea ; Milanesi, Ida ; Silvani, Antonio ; Gaviani, Paola ; Marchetti, Marcello ; Fariselli, Laura ; Solero, Carlo Lazzaro ; Maccagnano, Carmelo ; Casali, Cecilia ; Guzzetti, Sara ; Pollo, Bianca ; Ciusani, Emilio ; DiMeco, Francesco. / Prospective study of carmustine wafers in combination with 6-month metronomic temozolomide and radiation therapy in newly diagnosed glioblastoma : Preliminary results. In: Journal of Neurosurgery. 2013 ; Vol. 118, No. 4. pp. 821-829.
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abstract = "Object. Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemo-therapy with temozolomide. A combination of carmustine wafers with the Stupp treatment regimen has only been investigated in retrospective studies. Methods. In a single-institution prospective study, the authors assessed 12-month progression-free survival (PFS), toxicity, and overall survival in patients with glioblastoma treated with surgery, carmustine wafers, radiotherapy, and 6-month metronomic temozolomide chemotherapy. Thirty-five patients with de novo glioblastoma, between the ages of 18 and 70 years, and with Karnofsky Performance Scale scores of at least 70, were included in the study. Patients were followed monthly and assessed using MRI every 2 months. Results. After a median follow-up of 15 months, the median time to tumor progression was 12.5 months and median survival was 17.8 months. Due to toxicity (mostly hematological), 7 patients had to prematurely stop temozolomide treatment. Twenty-two patients developed Grade 3 CD4+ lymphocytopenia. Three patients developed oral-esophageal candidiasis, 2 developed pneumonia, and 1 developed a dorsolumbar zoster. Early intracranial hypertension was observed in 1 patient, and 1 was treated empirically for suspected brain abscess. One patient died of Legionella pneumonia soon after repeat surgery. Conclusions. Overall, this treatment schedule produced promising results in terms of PFS without a marked increase in toxicities as compared with the Stupp regimen. However, the gain in median survival using this schedule was less clear. Only prospective comparative trials will determine whether these preliminary results will translate into a long-term survival advantage with an acceptable toxicity profile.",
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T2 - Preliminary results

AU - Salmaggi, Andrea

AU - Milanesi, Ida

AU - Silvani, Antonio

AU - Gaviani, Paola

AU - Marchetti, Marcello

AU - Fariselli, Laura

AU - Solero, Carlo Lazzaro

AU - Maccagnano, Carmelo

AU - Casali, Cecilia

AU - Guzzetti, Sara

AU - Pollo, Bianca

AU - Ciusani, Emilio

AU - DiMeco, Francesco

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N2 - Object. Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemo-therapy with temozolomide. A combination of carmustine wafers with the Stupp treatment regimen has only been investigated in retrospective studies. Methods. In a single-institution prospective study, the authors assessed 12-month progression-free survival (PFS), toxicity, and overall survival in patients with glioblastoma treated with surgery, carmustine wafers, radiotherapy, and 6-month metronomic temozolomide chemotherapy. Thirty-five patients with de novo glioblastoma, between the ages of 18 and 70 years, and with Karnofsky Performance Scale scores of at least 70, were included in the study. Patients were followed monthly and assessed using MRI every 2 months. Results. After a median follow-up of 15 months, the median time to tumor progression was 12.5 months and median survival was 17.8 months. Due to toxicity (mostly hematological), 7 patients had to prematurely stop temozolomide treatment. Twenty-two patients developed Grade 3 CD4+ lymphocytopenia. Three patients developed oral-esophageal candidiasis, 2 developed pneumonia, and 1 developed a dorsolumbar zoster. Early intracranial hypertension was observed in 1 patient, and 1 was treated empirically for suspected brain abscess. One patient died of Legionella pneumonia soon after repeat surgery. Conclusions. Overall, this treatment schedule produced promising results in terms of PFS without a marked increase in toxicities as compared with the Stupp regimen. However, the gain in median survival using this schedule was less clear. Only prospective comparative trials will determine whether these preliminary results will translate into a long-term survival advantage with an acceptable toxicity profile.

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KW - Metronomic

KW - Oncology

KW - Radiation therapy

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