Deoxycoformycin-containing combination chemotherapy for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study (JCOG9109).
Aggressive adult T-cell leukemia-lymphoma (ATL) generally has a very poor prognosis. Deoxycoformycin (DCF, pentostatin), an inhibitor of adenosine deaminase, has shown promising therapeutic efficacy for ATL. To develop a new effective therapy against aggressive ATL, we carried out a multicenter phase II study of DCF-containing combination chemotherapy. Sixty-two previously untreated patients with ATL (34, 21, and 7 patients with diseases of the acute, lymphoma, and unfavorable chronic types, respectively) were enrolled, but 2 were ineligible because they were judged to be favorable chronic types. A regimen of 1 mg/m2 vincristine intravenously on days 1 and 8, 40 mg/m2 doxorubicin intravenously on day 1, 100 mg/m2 etoposide intravenously on days 1 through 3, 40 mg/m2 prednisolone orally on days 1 and 2, and 5 mg/m2 DCF intravenously on days 8, 15, and 22 was administered every 28 days for 10 cycles unless disease progression or toxic complications occurred. Fifty-two percent of 60 eligible patients responded (95% confidence interval [CI], 38%-65%), with 17 patients (28%) achieving a complete response (CR) (95% CI, 17%-41%) and 14 achieving a partial response. The CR rate was inferior to those of both the previous Japan Clinical Oncology Group (JCOG) study (JCOG8701, 43%), a 9-drug combination chemotherapy of the second generation, and the subsequent JCOG9303 study (35%), a granulocyte colony-stimulating factor-supported, dose-intensified, 9-drug regimen. The median survival time of the 60 eligible patients in JCOG9109 was 7.4 months, and the estimated 2-year survival rate was 15.5%; these results were identical with those of JCOG8701 but inferior to those of JCOG9303. Grade 4 neutropenia and infection of grade 3 or greater were frequent (67% and 22%, respectively), and treatment-related death was observed in 4 patients (7%), septicemia in 2, and cytomegalovirus pneumonia in 2. We conclude that DCF-containing combination chemotherapy is not a promising regimen against aggressive ATL.
Tsukasaki
Kunihiro
K
Nagasaki University, Nagasaki, Japan.
Tobinai
Kensei
K
Shimoyama
Masanori
M
Kozuru
Mitsuo
M
Uike
Naokuni
N
Yamada
Yasuaki
Y
Tomonaga
Masao
M
Araki
Koichi
K
Kasai
Masaharu
M
Takatsuki
Kiyoshi
K
Tara
Mitsutoshi
M
Mikuni
Chikara
C
Hotta
Tomomitsu
T
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D016190:Carboplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007564:Japan; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D015649:Pentostatin / Q000008:administration & dosage*; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy; D012955:Societies, Medical; D015996:Survival Rate; D016896:Treatment Outcome; D014751:Vindesine / Q000008:administration & dosage
D015649:Pentostatin; D003520:Cyclophosphamide; D016190:Carboplatin; D014751:Vindesine; D008727:Methotrexate