TY - JOUR
T1 - Phase I and pharmacokinetic study of preirradiation chemotherapy with BCNU, cisplatin, etoposide, and accelerated radiation therapy in patients with high-grade glioma
AU - Rajkumar, S. Vincent
AU - Buckner, Jan C.
AU - Schomberg, Paula J.
AU - Reid, Joel M.
AU - Bagniewski, Pamela J.
AU - Ames, Matthew M.
AU - Cascino, Terrence L.
AU - Marks, Randolph S.
N1 - Funding Information:
This study was supported in part by the Cancer Center Support Grant P30 CA15083 and the Linse-Bock Foundation.
PY - 1998/12/1
Y1 - 1998/12/1
N2 - Purpose: We conducted a Phase I study of bischloroethylnitrosourea (BCNU), cisplatin, and oral etoposide administered prior to and during accelerated hyperfractionated radiation therapy in newly diagnosed high- grade glioma. Pharmacokinetic studies of oral etoposide were also done. Methods and Materials: Patients started chemotherapy after surgery but prior to definitive radiation therapy (160 cGy twice daily x 15 days; 4800 cGy total). Initial chemotherapy consisted of BCNU 40 mg/m2 days 1-3, cisplatin 30 mg/m2 days 1-3 and 29-31, and etoposide 50 mg orally days 1-14 and 29- 42, repeated in 8 weeks concurrent with radiation therapy. BCNU 200 mg/m2 every 8 weeks x 4 cycles was given after radiation therapy. Results: Sixteen patients, 5 with grade 3 anaplastic astrocytoma and 11 with glioblastoma were studied. Grade 3-4 leukopenia (38%) and thrombocytopenia (31%) were dose- limiting. Other toxicities were anorexia (81%), nausea (94%), emesis (56%), alopecia (88%), and ototoxicity (38%). The maximum tolerated dose was BCNU 40 mg/m2 days 1-3, cisplatin 20 mg/m2 days 1-3 and 29-31, and oral etoposide 50 mg days 1-21 and 29-49 prior to radiation therapy and repeated in 8 weeks with the start of radiation therapy followed by BCNU 200 mg/m2 every 8 weeks for 4 cycles. Median time to progression and survival were 13 and 14 months respectively. Responses occurred in 2 of 9 (22%) patients with evaluable disease. In pharmacokinetic studies, all patients achieved plasma concentrations of >0.1 μg/ml etoposide (the in vitro radiosensitizing threshold), following a 50 mg oral dose. The mean ± SD 2 hr and 6 hr plasma concentrations were 0.92 ± 0.43 μg/ml and 0.36 ± 0.12 μg/ml, respectively. Estimated duration of exposure to >0.1 μg/ml etoposide was 10- 17 hr. Conclusions: Preirradiation chemotherapy with BCNU, cisplatin, and oral etoposide with accelerated hyperfractionated radiation therapy in high- grade gliomas is feasible and merits further investigation. Sustained radiosensitizing concentrations can be achieved with low oral doses of etoposide.
AB - Purpose: We conducted a Phase I study of bischloroethylnitrosourea (BCNU), cisplatin, and oral etoposide administered prior to and during accelerated hyperfractionated radiation therapy in newly diagnosed high- grade glioma. Pharmacokinetic studies of oral etoposide were also done. Methods and Materials: Patients started chemotherapy after surgery but prior to definitive radiation therapy (160 cGy twice daily x 15 days; 4800 cGy total). Initial chemotherapy consisted of BCNU 40 mg/m2 days 1-3, cisplatin 30 mg/m2 days 1-3 and 29-31, and etoposide 50 mg orally days 1-14 and 29- 42, repeated in 8 weeks concurrent with radiation therapy. BCNU 200 mg/m2 every 8 weeks x 4 cycles was given after radiation therapy. Results: Sixteen patients, 5 with grade 3 anaplastic astrocytoma and 11 with glioblastoma were studied. Grade 3-4 leukopenia (38%) and thrombocytopenia (31%) were dose- limiting. Other toxicities were anorexia (81%), nausea (94%), emesis (56%), alopecia (88%), and ototoxicity (38%). The maximum tolerated dose was BCNU 40 mg/m2 days 1-3, cisplatin 20 mg/m2 days 1-3 and 29-31, and oral etoposide 50 mg days 1-21 and 29-49 prior to radiation therapy and repeated in 8 weeks with the start of radiation therapy followed by BCNU 200 mg/m2 every 8 weeks for 4 cycles. Median time to progression and survival were 13 and 14 months respectively. Responses occurred in 2 of 9 (22%) patients with evaluable disease. In pharmacokinetic studies, all patients achieved plasma concentrations of >0.1 μg/ml etoposide (the in vitro radiosensitizing threshold), following a 50 mg oral dose. The mean ± SD 2 hr and 6 hr plasma concentrations were 0.92 ± 0.43 μg/ml and 0.36 ± 0.12 μg/ml, respectively. Estimated duration of exposure to >0.1 μg/ml etoposide was 10- 17 hr. Conclusions: Preirradiation chemotherapy with BCNU, cisplatin, and oral etoposide with accelerated hyperfractionated radiation therapy in high- grade gliomas is feasible and merits further investigation. Sustained radiosensitizing concentrations can be achieved with low oral doses of etoposide.
KW - Anaplastic astrocytoma
KW - BCNU
KW - Brain tumors
KW - Chemotherapy
KW - Cisplatin
KW - Etoposide
KW - Glioblastoma
KW - Radiation therapy
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U2 - 10.1016/S0360-3016(98)00352-6
DO - 10.1016/S0360-3016(98)00352-6
M3 - Article
C2 - 9869217
AN - SCOPUS:0032412554
SN - 0360-3016
VL - 42
SP - 969
EP - 975
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 5
ER -