title: Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma.
abstract: Sixty patients with advanced multiple myeloma received 2-6 monthly treatment courses combining hyperfractionated cyclophosphamide (300 mg/m2 i.v. over 3 h q 12 h x 6, d 1-3) with pulsed dexamethasone (20 mg/m2/d p.o., d 1-4, 9-12, 17-20) and once daily thalidomide at individually escalating doses (100-400 mg/d) depending on tolerability (HyperCDT). Responding patients were maintained on daily thalidomide and monthly dexamethasone pulses. Complete, partial and minor response rates were 4%, 68% and 12% respectively; overall response rate was 84% (efficacy analysis). Median event-free and overall survival was 11 and 19 months respectively. During at least one treatment cycle, 67% of patients experienced grade 4 neutropenia resulting in 17% grade 3 and 9% grade 4 infections. Side-effects, presumably related to thalidomide, included neuropathy (40% grade 2, 16% grade 3), constipation (17%), oedema (5%), bradycardia (5%), skin reactions (3%), cerebrovascular events (5%) and deep vein thromboses (8%). Thromboses were not related to known thrombophilic risk factors. Four patients with prior myeloma therapy > 50 months developed myelodysplastic syndrome or secondary acute myeloid leukaemia 2-4 months after study entry. HyperCDT is a highly active and reasonably well-tolerated salvage regimen in advanced or refractory multiple myeloma.
authors.affiliation: Department of Medicine/Haematology and Oncology, University of Muenster, Albert-Schweitzer-Strasse 33, 48129 Muenster, Germany.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Kropff
authors.forename: Nicola
authors.initials: N
authors.lastname: Lang
authors.forename: Guido
authors.initials: G
authors.lastname: Bisping
authors.forename: Nicole
authors.initials: N
authors.lastname: Dominé
authors.forename: Georg
authors.initials: G
authors.lastname: Innig
authors.forename: Markus
authors.initials: M
authors.lastname: Hentrich
authors.forename: Manfred
authors.initials: M
authors.lastname: Mitterer
authors.forename: Thomas
authors.initials: T
authors.lastname: Südhoff
authors.forename: Roland
authors.initials: R
authors.lastname: Fenk
authors.forename: Christian
authors.initials: C
authors.lastname: Straka
authors.forename: Achim
authors.initials: A
authors.lastname: Heinecke
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Koch
authors.forename: Helmut
authors.initials: H
authors.lastname: Ostermann
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Joachim
authors.initials: J
authors.lastname: Kienast
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000139:chemically induced; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007951:Leukemia, Myeloid / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009190:Myelodysplastic Syndromes / Q000139:chemically induced; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D009894:Opportunistic Infections / Q000139:chemically induced; D012008:Recurrence; D016019:Survival Analysis; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000139:chemically induced
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; D003520:Cyclophosphamide