title: Treatment of refractory Hodgkin's disease with high-dose cytosine arabinoside and mitoxantrone in combination. Results of a clinical phase II study of the German Hodgkin Study Group.
abstract: In the present study, the activity and side effects of high-dose cytosine arabinoside (HD-Ara-C) in combination with mitoxantrone (mitox) (HAM) was evaluated in 32 heavily pretreated patients with refractory Hodgkin's disease. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours days 1 and 2 and mitox 10 mg/m2/d days 3 to 5. In subsequent steps, HD-Ara-C was escalated to six and eight doses for 3 and 4 days, respectively, and mitox to four doses on days 2 to 5. Thirty-two patients 17 to 55 years of age entered the study. Twenty-five cases presented with extranodal disease and disseminated organ involvement and 21 revealed systemic (B) symptoms. Eighteen patients (56%) responded with five complete and 13 partial remissions, ten patients (31%) had refractory disease, and four patients died from infections during treatment-induced cytopenia. The predominant toxicity was severe myelosuppression in all patients with major infections occurring during 55% of treatment courses. Ten of the responding 18 patients underwent subsequent autologous (n = 9) or allogeneic bone marrow transplant (BMT). Seven of these cases are currently alive at 5+ to 22+ months, six of them without evidence of disease. Among the remaining eight patients not receiving BMT, three are alive at 6+ to 19+ months from the initiation of HAM, two of them in ongoing remissions of 2+ and 5+ months' duration. Two patients died from transplant-related complications and six patients succumbed to progressive disease following relapse. The median survival for all treated patients is 6.2 months. These data indicate that HAM has a significant activity in refractory Hodgkin's disease. However, the substantial side effects and the lack of an obvious superiority to alternative, less intensive regimens limits the further application of the two-drug combination in its present form. Modifications in timing and dosage and the addition of hematopoietic growth factors will be evaluated in subsequent trials.
authors.affiliation: Department of Internal Medicine, University of Münster, Fed. Rep. Germany.
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
authors.forename: N
authors.initials: N
authors.lastname: Schmitz
authors.forename: M
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: K H
authors.initials: KH
authors.lastname: Pflüger
authors.forename: J
authors.initials: J
authors.lastname: Ollech-Chwoyka
authors.forename: C
authors.initials: C
authors.lastname: Tirier
authors.forename: G
authors.initials: G
authors.lastname: Maschmeyer
authors.forename: H
authors.initials: H
authors.lastname: Kirchner
authors.forename: T
authors.initials: T
authors.lastname: Wagner
authors.forename: P
authors.initials: P
authors.lastname: Koch
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction
chemical_list: D003561:Cytarabine; D008942:Mitoxantrone