Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma

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Abstract
Summary. 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 × 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.