Deoxycoformycin-containing combination chemotherapy for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study (JCOG9109).

Abstract

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.

• Authors: Kunihiro Tsukasaki, Kensei Tobinai, Masanori Shimoyama, Mitsuo Kozuru, Naokuni Uike, Yasuaki Yamada, Masao Tomonaga, Koichi Araki, Masaharu Kasai, Kiyoshi Takatsuki, Mitsutoshi Tara, Chikara Mikuni, Tomomitsu Hotta, Lymphoma Study Group of the Japan Clinical Oncology Group
• Journal: International journal of hematology (Int J Hematol) Vol. 77 Issue 2 Pg. 164-70 (Feb 2003) ISSN: 0925-5710 [Print] Japan
• PMID: 12627852 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Pentostatin
• Cyclophosphamide
• Carboplatin
• Vindesine
• Methotrexate

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, toxicity)
• Carboplatin (administration & dosage)
• Cyclophosphamide (administration & dosage)
• Female
• Humans
• Japan
• Leukemia-Lymphoma, Adult T-Cell (complications, drug therapy, mortality)
• Male
• Methotrexate (administration & dosage)
• Middle Aged
• Pentostatin (administration & dosage)
• Remission Induction (methods)
• Salvage Therapy
• Societies, Medical
• Survival Rate
• Treatment Outcome
• Vindesine (administration & dosage)