An evaluation of factors predicting long-term response to thalidomide in 234 patients with relapsed or resistant multiple myeloma
| Autor: | Joanna Mańko, Aleksander B. Skotnicki, Andrzej Hellmann, Iwona Hus, K. Sulek, Tadeusz Robak, Hanna Ciepluch, Maria Soroka-Wojtaszko, Dariusz Jawniak, Anna Dmoszynska, Lech Konopka, Janusz Kloczko, Marek Hus, Teresa Wolska-Smolen |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Time Factors medicine.medical_treatment Plasma cell Proinflammatory cytokine Hemoglobins Clinical pretreatment parameters chemistry.chemical_compound Predictive Value of Tests thalidomide Albumins Internal medicine medicine Humans long-term response Survival rate Multiple myeloma Aged Aged 80 and over Chemotherapy business.industry Middle Aged Prognosis medicine.disease Thalidomide Survival Rate multiple myeloma Vascular endothelial growth factor Treatment Outcome medicine.anatomical_structure chemistry Drug Resistance Neoplasm Immunology Female Bone marrow Neoplasm Recurrence Local beta 2-Microglobulin business Immunosuppressive Agents medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Multiple myeloma (MM) is a plasma cell malignancy characterised by the accumulation of long-lasting plasma cells in the bone marrow and/or extramedullar sites. Conventional chemotherapy produces an overall response rate of 40–60% with a median survival of about 3.5 years. Aggressive, high-dose chemotherapy, bone marrow transplantation and intensive supportive care allowed for an increase in survival of up to 4–6 years. However, patients with primary resistant disease and those who relapse after a response have a median survival duration of 15 and 12 months, respectively. The disease still remains incurable and almost all patients eventually relapse and become resistant to cytostatics. New treatments have recently been developed to overcome drug resistance, which target the MM cell, the MM cell–host interaction and the bone marrow (BM) microenvironment. Thalidomide (THAL) and its immunomodulatory derivatives are examples of such agents that target the tumour cell in its BM milieu, and which make possible responses even in refractory or relapsed MM. THAL, used as a sedative drug in the 1960s, was withdrawn from clinical use because of its severe teratogenicity but has been reintroduced because of its immunomodulating and antiangiogenic properties (Rajkumar and Witzig, 2000). The exact mechanism of THAL action on MM is still unclear. Some postulated effects of THAL are: the inhibition of proangiogenic cytokines, such as vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF) (Dmoszynska et al, 2000; Kyle and Rajkumar, 2001) and the downregulation of the secretion of proinflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor (TNF) (Moreira et al, 1993; Turk et al, 1996); upregulation of adhesion molecules (Geitz et al, 1996) and the stimulation of cytotoxic T-cell proliferation and the secretion of interferon-γ and interleukin-2 (Haslett et al, 1998). First reports concerning the application of THAL in MM were published in 1999 by Singhal et al (1999). Since then, the efficacy of THAL in refractory or relapsed MM patients was confirmed by many other authors (Juliusson et al, 2000; Kneller et al, 2000; Barlogie et al, 2001a, 2001b; Hus et al, 2001; Kumar et al, 2003) with a response rate ranging from 32 to 64%. However, many questions, such as that of the optimal dose, duration of therapy and the factors predicting response to THAL treatment are still only partially answered. The aim of this study was to assess the prognostic value of pretreatment clinical and laboratory parameters in refractory or relapsed MM patients with a long-term response to THAL, lasting at least 18 months. |
| Databáze: | OpenAIRE |
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