Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma

Offidani, Massimo; Corvatta, Laura; Piersantelli, Maria Novella; Visani, Giuseppe; Alesiani, Francesco; Brunori, Marino; Galieni, Piero; Catarini, Massimo; Burattini, Maurizio; Centurioni, Riccardo; Ferranti, Mario; Rupoli, Serena; Scortechini, Anna Rita; Giuliodori, Luciano; Candela, Marco; Capelli, Debora; Montanari, Mauro; Olivieri, Attilio; Poloni, Antonella; Polloni, Claudia; Marconi, Marco; Leoni, Pietro

doi:10.1182/blood-2006-03-013086

Cited by 97 publications

(49 citation statements)

References 20 publications

(29 reference statements)

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“…This raises the question whether vincristine and/or the anthracycline component of the regimen were responsible for the durability of response. This question may have been answered by a study recently reported by Offidani et al, 30 who investigated the use of thal/dex plus pegylated liposomal doxorubicin in 59 patients with newly diagnosed or recurrent myeloma. The overall response rate in their study was 79% (30% complete responses, 10% very good partial responses, 39% partial responses); and at a median follow-up of 12 months, the projected 2-year OS and PFS rates were 73% and 50%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma

Rifkin

Gregory

Mohrbacher

et al. 2006

Cancer

119

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Aquathermolysis of bitumen occurs when it is thermally cracked in the presence of water. Current in situ technologies for bitumen production, such as Cyclic Steam Stimulation and Steam‐Assisted Gravity Drainage, inject high pressure, high temperature steam in the reservoir to heat the bitumen which in turn lowers its viscosity enabling flow to a production well. Thus, the major physical effect of steam is the heating of bitumen which mobilises it. Beyond physical interactions, chemical effects also result: steam heating produces acid gases, such as carbon oxides, sulphur dioxide and hydrogen sulphide along with small amounts of hydrogen and methane. For steam‐based in situ bitumen recovery processes, nearly all analyses, including simple drainage theories and thermal reservoir simulations, focus solely on the physical processes: heat transfer, fluid flow and thermodynamic equilibrium. However, steam chambers are also underground reactors: bitumen aquathermolysis occurs due to high temperatures and water saturation. Here, we describe a new in situ aquathermolysis reaction scheme for Athabasca bitumen to predict hydrogen, methane, carbon oxides, hydrogen sulphide and other heavy molecular weight hydrocarbons. Reaction parameters were fitted against one experimental data set and validated against other independent experimental data sets, both from the literature. Our results indicate that, to more accurately predict gas compositions and rates, the effects of aquathermolysis should be taken into account in reservoir modelling. © 2012 Canadian Society for Chemical Engineering

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Section: Discussionmentioning

confidence: 99%

Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma

Rifkin

Gregory

Mohrbacher

et al. 2006

Cancer

119

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“…In a phase 2 study, 44 the PR rate was 88%, including 34% CR. Patients with impaired renal function achieved PR, and renal function was improved or restored.…”

Section: Newly Diagnosed MMmentioning

confidence: 95%

“…Most infectious complications occurred during the first 3 courses of treatment; prophylaxis with ciprofloxacin reduced the infection rate to less than 10%. 24,44 Liver and renal function Thalidomide-associated hepatitis, resolved after drug withdrawal, has been reported, although it is rare. 76 Since thalidomide is spontaneously and nonspecifically hydrolyzed, plasma concentrations should not change in patients with compromised liver function.…”

Section: Hematologic Side Effects and Infectionsmentioning

confidence: 99%

Thalidomide for treatment of multiple myeloma: 10 years later

Palumbo

Façon

Sonneveld

et al. 2008

Blood

283

187

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Thalidomide, bortezomib, and lenalidomide have recently changed the treatment paradigm of myeloma. In young, newly diagnosed patients, the combination of thalidomide and dexamethasone has been widely used as induction treatment before autologous stem cell transplantation (ASCT). In 2 randomized studies, consolidation or maintenance with low-dose thalidomide has extended both progression-free and overall survival in patients who underwent ASCT at diagnosis. In elderly, newly diagnosed patients, 3 independent randomized studies have reported that the oral combination of melphalan and prednisone plus thalidomide (MPT) is better than the standard melphalan and prednisone (MP). These studies have shown better progression-free survival, and 2 have shown improved overall survival for patients assigned to MPT. In refractory-relapsed disease, combinations including thalidomide with dexamethasone, melphalan, doxorubicin, or cyclophosphamide have been extensively investigated. The risks of side effects are greater when thalidomide is used in combination with other drugs. Thromboembolism and peripheral neuropathy are the major concern. The introduction of anticoagulant prophylaxis has reduced the rate of thromboembolism to less than 10%. Immediate thalidomide dose reduction or discontinuation when paresthesia is complicated by pain or motor deficit has decreased the severity of neuropathy. Future studies will define the most effective or the best sequence of combinations which could improve life expectancy. (Blood. 2008;111:3968-3977)

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“…Of greater interest may be the combination of thalidomide, pegylated liposomal doxorubicin, and dexamethasone (ThaDD ; Table 6), which was studied in 50 patients over the age of 65. 49 Grade 3 and 4 events seen in at least 10% of patients included infections, thromboembolic complications, neutropenia, and constipation. An overall response rate of 84% was reported, with 56% of patients achieving at least a very good PR.…”

Section: Regimens Not Based On Mpmentioning

confidence: 99%

Initial Therapy of Multiple Myeloma Patients Who Are Not Candidates for Stem Cell Transplantation

Orłowski¹

2006

Hematology

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Multiple myeloma patients deemed to not be candidates for high-dose therapy followed by stem cell rescue who nonetheless need chemotherapy have traditionally received an oral regimen combining melphalan and prednisone. With the advent of novel agents, however, such as immunomodulatory drugs and proteasome inhibitors that are active in the relapsed/refractory setting, there has been an impetus to incorporate these new options into front-line therapy. Several phase II studies have recently revealed that addition of either thalidomide, lenalidomide, or bortezomib to melphalan and prednisone increased the overall and complete response rates, albeit at the cost of some increased toxicity. Randomized phase III studies of melphalan and prednisone with thalidomide have already shown that, compared to melphalan and prednisone alone, the three-drug regimen prolonged time to progression and overall survival in this population, thereby defining a new standard of care. Moreover, our increasing knowledge of the molecular role that cytogenetic abnormalities play in the biology of multiple myeloma and our growing chemotherapeutic armamentarium are beginning to allow us to rationally select therapies based on these characteristics of each patient's disease. Such a risk-and molecular-adapted strategy to the therapy of multiple myeloma promises to revolutionize and personalize our care of these patients and bring us closer to a cure for this disease.Using the diagnostic criteria recommended by the International Working Group, patients with multiple myeloma are classified as having either asymptomatic or symptomatic (Table 1) disease. 1 The latter population, generally considered candidates for a chemotherapy-based intervention, are then further divided into those who either are or are not eligible for high-dose chemotherapy followed by stem cell rescue. 2 Criteria that are weighed to help make this second distinction have generally included age, performance status, and co-morbid medical conditions. 2 There is some variability in these parameters and how they are applied, since studies examining stem cell transplantation have used different criteria. In regard to age, for example, which is the most objective of these measures, initial studies tended to enroll patients younger than 65 years of age, 3 while more recent studies suggest that transplant is safe in at least some who are over the age of 70 (for example 4,5 ). On the other hand, data suggesting that patients with poor-risk chromosomal features have a short time to progression after autologous transplantation have led to suggestions that even younger patients with these abnormalities may not be candidates for standard approaches. Nonetheless, as little as two years ago, there was general agreement that the standard of care for patients who were not eligible for transplantation and yet needed chemotherapy was melphalan

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Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma

Cited by 97 publications

References 20 publications

Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma

Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma

Thalidomide for treatment of multiple myeloma: 10 years later

Initial Therapy of Multiple Myeloma Patients Who Are Not Candidates for Stem Cell Transplantation

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