A phase I study of cisplatin, temozolomide and thalidomide in patients with malignant brain tumors.
BACKGROUND
There is pre-clinical evidence of synergism between cisplatin (P) and temozolomide (T) due to higher inhibition by T of O6-alkyl-guanine-alkyltransferase (AGAT), an enzyme involved in the mismatch repair system. T and P are active against malignant gliomas while thalidomide (TH) is emerging as an inhibitor of angiogenesis.


METHODS
Triplets of patients with malignant brain tumors received escalating doses of P, T and TH up to the dose-limiting-toxicity (DLT) and the maximal tolerated dose (MTD).


RESULTS
Seventeen patients were enrolled and a total of 74 cycles were delivered. The MTD was P 75 mg/m2 day 1 and T 150 mg/m2 days 1 to 5 every 21 days with a concomitant 200 mg total daily dose of TH. DLT events were G4 thrombocytopenia and febrile neutropenia.


CONCLUSIONS
Concomitant administration of P 75 mg/m2 day 1, T 150 mg/m2 days 1 to 5 every 21 days and concomitant TH at a total daily dose of 150 mg is feasible and safe. Early efficacy data are encouraging and a phase II study is ongoing.
Zustovich
Fable
F
Istituto Oncologico Veneto/IRCCS, Via Gattamelata n. 64, 35128 Padova, Italy. fable.zustovich@istitutoncologicoveneto.it
Cartei
Giuseppe
G
Ceravolo
Renato
R
Zovato
Stefania
S
Della Puppa
Alessandro
A
Pastorelli
Davide
D
Mattiazzi
Martina
M
Bertorelle
Roberta
R
Gardiman
Marina Paola
MP
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects
D013792:Thalidomide; D003606:Dacarbazine; D002945:Cisplatin; D000077204:Temozolomide