Treatment of recurrent malignant supratentorial astrocytomas with carboplatin and etoposide combined with recombinant mutant human tumor necrosis factor-alpha.
BACKGROUND
This study assesses the safety, tolerance and preliminary efficacy of combined treatment with carboplatin, etoposide and recombinant human mutant tumor necrosis factor-alpha (TNF-SAM2) for recurrent malignant supratentorial astrocytomas at first relapse.


METHODS
Carboplatin was administered intravenously at a dose of 400 mg/m2 on Day 1, while etoposide was administered intravenously at a dose of 100 mg/m2 from Day 1 to Day 3 for 3 days. From Day 7, 80x10(4) U/m2 TNF-SAM2 was given intravenously for up to 5 injections for 2 weeks. Treatment was repeated every 8 to 12 weeks.


RESULTS
Ten patients previously treated with surgery, radiation therapy and chemotherapy with a nitrosourea (ranimustine: MCNU) for malignant astrocytomas received this regimen for up to four cycles. Three patients with anaplastic astrocytomas, one patient with anaplastic oligoastrocytoma and 6 patients with glioblastomas (3 men and 7 women), aged 27 to 69 years, were eligible and were evaluated for response and toxicity. Grade 2 and 3 hematological toxicities occurred in 4 (40%) and 2 patients (20%), respectively. Grade 2 hepatic toxicity was observed in two patients. Of 9 evaluable patients, three (33%), including one glioblastoma, partially responded to the treatment (PR) with time to tumor progression (TTP) of 231, 121 and 57 weeks, respectively. Two patients had stable disease (SD), while 4 glioblastomas (44%) had progressive disease (PD) with TTP values of 11, 15, 6 and 12 weeks, respectively.


CONCLUSIONS
These results suggest that combined therapy with carboplatin, etoposide and recombinant mutant TNF-alpha in this patient population seems to be safe and acceptable and may benefit those with recurrent anaplastic astrocytomas. These intriguing clinical observations warrant a properly stratified randomized trial to determine whether this approach can provide therapeutic benefits and improve survival.
Yamamoto
Masaaki
M
Department of Neurosurgery, Fukuoka University School of Medicine, Japan. masaaki@fukuoka-u.ac.jp
Oshiro
Shinya
S
Tsugu
Hitoshi
H
Hirakawa
Katsuyuki
K
Ikeda
Kohichi
K
Soma
Gen-Ichiro
G
Fukushima
Takeo
T
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D001921:Brain / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018579:Patient Selection; D011994:Recombinant Proteins / Q000008:administration & dosage; D015173:Supratentorial Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005047:Etoposide; D016190:Carboplatin