Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma.
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.
Kropff
Martin H
MH
Department of Medicine/Haematology and Oncology, University of Muenster, Albert-Schweitzer-Strasse 33, 48129 Muenster, Germany.
Lang
Nicola
N
Bisping
Guido
G
Dominé
Nicole
N
Innig
Georg
G
Hentrich
Markus
M
Mitterer
Manfred
M
Südhoff
Thomas
T
Fenk
Roland
R
Straka
Christian
C
Heinecke
Achim
A
Koch
Olaf M
OM
Ostermann
Helmut
H
Berdel
Wolfgang E
WE
Kienast
Joachim
J
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
D013792:Thalidomide; D003907:Dexamethasone; D003520:Cyclophosphamide