Myeloproliferative Neoplasms by Tiziano Barbui & Ayalew Tefferi

Author:Tiziano Barbui & Ayalew Tefferi
Language: eng
Format: epub
Publisher: Springer Berlin Heidelberg, Berlin, Heidelberg

11.4 Intolerance/Refractoriness to Other First-Line Drugs

11.4.1 Interferon

Fever and flu-like symptoms develop in most patients treated with conventional interferon-alpha; these can be usually managed with prophylactic assumption of paracetamol (Kiladjian et al. 2008). These manifestations, together with other more severe toxicities represented by myalgia, weight loss, new appearance or worsening of autoimmune diseases, and severe depression, caused discontinuation of the treatment in 14–42% and 10–35% of PV and ET patients, respectively, according to a number of small trials (reviewed in, Kiladjian et al. 2011). In the largest series reported by R.T. Silver, that included 55 PV patients treated with conventional forms of interferon-alpha, only 8 (15%) discontinued the treatment (Silver 2006).

Pegylated forms of interferon-alpha might have better tolerance in both PV and ET, according to recent studies (Kiladjian et al. 2006a; Quintas-Cardama et al. 2009). In the largest of these, that enrolled 40 PV and 39 ET patients and used PEG-IFN-alpha-2a (Quintas-Cardama et al. 2009), 96% of patients developed some toxicity, but this was generally grade 1 or 2 and was noted to be dependent on the initial dose (minimal in those who started at 90 μg weekly). The most frequent grade 3 or 4 toxicity, which occurred in 20% of patients, was represented by neutropenia. A total of 22% of the PV patients experienced related events necessitating discontinuation of therapy. On the other hand, of the 37 PV patients reported by Kiladjian et al. (2006a), 13 (35%) had to discontinue the treatment. Another preparation of pegylated interferon, alpha-2b, seems to be even less tolerated compared to the previous one. This interferon has been used in 36 patients with high-risk ET (Langer et al. 2005); treatment was stopped in ten patients (28%) due to grade 1–2 toxicity. In another study, 11 ET patients, either high-risk or refractory to hydroxyurea or anagrelide, received pegylated interferon-alpha-2b for a median duration of 9 months. One patient discontinued therapy at 4 months because of persistent grade 3 fatigue and a second at 5 months because of anxiety and depression (Alvarado et al. 2003). Finally, in the study of Samuelsson et al. (Samuelsson et al. 2006), that enrolled 21 patients each with PV and ET, the rate of discontinuation was as high as 30% and 55%, respectively. In brief, it can be expected that at least 20–25% of the patients who receive pegylated interferon as first-line therapy have to switch to second-line drugs due to poor tolerance or severe side effects.

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