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

Abstract

Summary. Sixty patients with advanced multiple myeloma received 2-6 monthly treatment courses combining hyperfractionated cyclophosphamide (300 mg/m 2 i.v. over 3 h q 12 h · 6, d 1-3) with pulsed dexamethasone (20 mg/m 2 /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.

The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma

“…19 In addition, the regimen was tolerated well and the number and severity of secondary effects were acceptable. Similar results have been reported by other groups with different combinations, [24][25][26][27][28] but the series of patients are usually small and, more importantly, the follow-up is too short to sustain definitive conclusions in the long-term effects of these treatments. Here, we report on extended experience with ThaCyDex including a total of 71 MM patients with refractory or relapsed MM.…”

“…alkylating agents) to thalidomide and dexamethasone is currently being explored by several groups. Thus, the combination of thalidomide, cyclophosphamide and dexamethasone was tested by the German group 27 as a second-line therapy with a high response rate (72% of PR). However, in this study, cyclophosphamide is used intravenously in intermediate doses, which results in a high toxicity (e.g.…”

Novel targeted drugs for the treatment of multiple myeloma: from bench to bedside

“…[27][28][29][30][31] The observation of synergism formed the rationale for its use with dexamethasone, where potent antitumour effects were seen in patients refractory to both drugs given previously as single agents, and with chemotherapy. [32][33][34][35] The efficacy of thalidomide as salvage treatment prompted to explore its use in untreated MM. [36][37][38][39][40][41] Rajkumar et al 36 reported significant activity in indolent and smouldering MM.…”

Single-agent thalidomide for treatment of first relapse following high-dose chemotherapy in patients with multiple myeloma

“…1,2,4-8 These patients need a more toxic combination therapy of thalidomide with dexamethasone and chemotherapy, which is associated with higher toxicity. [1][2][3] Even though thalidomide has been shown to be very effective in our study population, we could identify a subgroup of patients with a high risk of relapse. An important finding of this study was that patients who relapsed within the first year after HDT had an inferior outcome in comparison to patients who had remissions lasting more than 12 months.…”

“…1,2 Thalidomide monotherapy can induce remissions in about one-third of relapsing or refractory patients 1,2,4-8 and combinations of thalidomide with dexamethasone and/or chemotherapy can further improve response rates in these patients. [1][2][3] Abnormal cytogenetics, high plasma cell labeling index, IgA isotype, high levels of LDH or beta2-microglobulin as well as low hemoglobulin, platelet count or albumin have been identified in different studies as adverse prognostic factors for outcome after treatment with thalidomide in patients with relapsed or refractory MM. [4][5][6][7][8] Apart from results of patients with advanced and heavily pretreated disease, studies have shown efficiency of thalidomide treatment in untreated patients.…”