Ruxolitinib in clinical practice for therapy of myelofibrosis: Single USA center experience following Food and Drug Administration approval

Novel conformationally constrained pyrazole derivatives as potential anti-cancer agents

“…In particular, numerous synthetic small molecules from various groups of azaheterocycles have been reported to influence carcinogenesis and are currently in clinical trials [2,3] or approved for the treatment of various cancer types [3,4]. Indicatively, carbazoles possessing a unique tricyclic ring system have been permitted for the treatment of cancer [5], while phenazines [6] and several piperazines [7] have been found to display IC 50 values in the nanomolar range against quinone reductase inhibitors.…”

Tips on using ruxolitinib in everyday practice as therapy for myelofibrosis

“…[1] The presence of anemia, however, is not a contraindication for use of ruxolitinib. As reported by Geyer and colleagues,[8] the addition of another therapeutic agent to improve anemia can be attempted (danazol, erythropoietin, or low-dose thalidomide). Indeed, there is no contraindication to using ruxolitinib.…”

“…[4] Preliminary results of an ongoing Phase II study in patients with platelets between 50 × 10 9 /l and 100 × 10 9 /l reveal the benefits of therapy starting at a low dose of 5 mg BID and increasing to 10 mg BID if not overly myelosupressive, which was possible in the majority of the patients. [9] A similar approach is possible in patients with significant anemia, as reported by Geyer and colleagues[8]: starting with a lower dose and increasing as possible. A few important points should be mentioned here: 1) ruxolitinib should be used in BID schedule due to its short half-life; single daily dosing was shown to be ineffective.…”

“…[4] As reported by Geyer,[8] close follow-up of patients during the first 2–3 months of therapy is mandatory, and proactive dose adjustments are recommended in order to maintain patients on therapy with an effective dose and without interruptions. While 5 mg BID can be used transiently in a case of significant myelosuppression, 10 mg BID or higher, has been shown to be effective long term.…”

“…Discontinuations for myelosuppresssion are rare, as reported in previous clinical studies and by Geyer and colleagues as well. [4,8]…”