Prospective study of carmustine wafers in combination with 6-month metronomic temozolomide and radiation therapy in newly diagnosed glioblastoma: preliminary results.
OBJECTIVE
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 radiochemotherapy 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.
Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy. salmaggi@istituto-besta.it
Andrea
A
Salmaggi
Ida
I
Milanesi
Antonio
A
Silvani
Paola
P
Gaviani
Marcello
M
Marchetti
Laura
L
Fariselli
Carlo Lazzaro
CL
Solero
Carmelo
C
Maccagnano
Cecilia
C
Casali
Sara
S
Guzzetti
Bianca
B
Pollo
Emilio
E
Ciusani
Francesco
F
Dimeco
D059250:Administration, Metronomic; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D002330:Carmustine / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000401:mortality / Q000628:therapy*; D006801:Humans; D017567:Karnofsky Performance Status; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D011446:Prospective Studies; D011878:Radiotherapy; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D002330:Carmustine; D000077204:Temozolomide