title: Feasibility of salvage chemotherapy for refractory or relapsed non-Hodgkin's lymphoma with two topoisomerase II inhibitors, MST-16 and VP-16. MST-16 Study Group.
abstract: A feasibility study was carried out on the treatment for refractory and relapsed non-Hodgkin's lymphomas with a combination of two oral topoisomerase II inhibitors, MST-16 and VP-16. On the basis of the synergistic activity in preclinical studies and the schedule dependency in these drugs, low-dose and long-term administration was planned. For the anticipated myelosuppression, two different regimens were designed as an open label trial in this study. In Regimen I, 400 mg of MST-16 combined with 25 mg of VP-16 was administered daily. With this regimen, the response rate (RR)/median time to tumor progression (TTP) in all evaluable patients was 50% (2/4)8.5 months in low grade (indolent) lymphoma and 60% (6/10)/5.2 months in intermediate/high grade (aggressive) lymphomas. In Regimen II, 400 mg of MST-16 combined with 25 mg of VP-16 was administered intermittently (3 days a week or every other day). With this regimen, there was an RR/median TTP of 60% (3/5)/7.0 months in indolent lymphoma and 33.3% (4/12)/1.1 months in aggressive lymphoma. A major side effect in both of these regimens was myelosuppression, with the incidence of grades 3 and 4 toxicity being higher in Regimen I than in Regimen II. The other side effects were uncommon and not severe. These findings indicated that two regimens were tolerated well and were promising for refractory and relapsed aggressive non-Hodgkin's lymphomas. To define the anti-tumor activity and safety of these regimens precisely, large-scale prospective randomized trials are necessary.
authors.affiliation: Department of Hematology and Chemotherapy, Aichi Cancer Center, Nagoya, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kagami
authors.forename: Y
authors.initials: Y
authors.lastname: Ariyoshi
authors.forename: A
authors.initials: A
authors.lastname: Horiuchi
authors.forename: A
authors.initials: A
authors.lastname: Kanamaru
authors.forename: Y
authors.initials: Y
authors.lastname: Kano
authors.forename: T
authors.initials: T
authors.lastname: Naoe
authors.forename: M
authors.initials: M
authors.lastname: Oguro
authors.forename: R
authors.initials: R
authors.lastname: Ohno
authors.forename: K
authors.initials: K
authors.lastname: Sampi
authors.forename: S
authors.initials: S
authors.lastname: Shirakawa
authors.forename: T
authors.initials: T
authors.lastname: Masaoka
authors.forename: H
authors.initials: H
authors.lastname: Furue
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D012008:Recurrence; D016879:Salvage Therapy; D059005:Topoisomerase II Inhibitors
chemical_list: D010879:Piperazines; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; C057773:sobuzoxane