Chronic Fatigue Syndrome: Ferrajoli A

Jabbour E, Kantarjian H, Cortes J, Thomas D, Garcia-Manero G, Ferrajoli A, Faderl S, Richie MA, Beran M, Giles F, Verstovsek S. · Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. · Cancer. · Pubmed #17849460 links to  free full text

Abstract: BACKGROUND: Interferon-alpha (IFN-alpha) has shown significant activity in the treatment of BCR-ABL-negative myeloproliferative disorders (MPDs), particularly essential thrombocythemia (ET) and polycythemia vera (PV). PEG-IFN-alpha-2b is a pegylated IFN-alpha-2b with a significant advantage over nonpegylated form in that it is administered once a week. METHODS: Thirty-eight patients with BCR-ABL-negative MPDs were treated with PEG-IFN-alpha-2b, given subcutaneously weekly, at the starting dose of 3 microg/kg/wk for the first 14 patients and then 2 microg/kg/wk for the next 24 patients, with intent to treat patients as long as they benefited from the therapy. RESULTS: Median age was 54 years. Patient diagnoses were: 13 (34%) ET; 11 (29%) primary myelofibrosis (PMF); 5 (13%) BCR-ABL-negative chronic myeloid leukemia (CML); 4 (10.5%) hypereosinophilic syndrome (HES); 4 (10.5%) PV; and 1 (3%) unclassified myeloproliferative disease (uMPD). Recorded grade 3-4 toxicities were related to fatigue, myelosuppression, and musculoskeletal pain. Ten (26%) patients stopped treatment because of toxicity. Thirteen (34%) patients achieved a complete remission, and 4 (11%) achieved a partial response. Only 1 patient with PMF responded. Median time to response was 5 months. Median duration of response was 20 months. Three patients had a sustained response for >24 months. CONCLUSIONS: PEG-IFN-alpha-2b, with proper dose modifications, is effective in controlling disease in a significant proportion of BCR-ABL-negative MPD patients, particularly ET and PV. However, toxicities encountered with PEG-IFN-alpha-2b therapy are similar to those obtained with conventional IFN-alpha, thus limiting the duration of therapy.

Yee KW, Zeng Z, Konopleva M, Verstovsek S, Ravandi F, Ferrajoli A, Thomas D, Wierda W, Apostolidou E, Albitar M, O'Brien S, Andreeff M, Giles FJ. · Authors' Affiliations: Departments of Leukemia and Blood and Marrow Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, Texas. · Clin Cancer Res. · Pubmed #16951235 links to  free full text

Abstract: PURPOSE: Everolimus (RAD001, Novartis), an oral derivative of rapamycin, inhibits the mammalian target of rapamycin (mTOR), which regulates many aspects of cell growth and division. A phase I/II study was done to determine safety and efficacy of everolimus in patients with relapsed or refractory hematologic malignancies. EXPERIMENTAL DESIGN: Two dose levels (5 and 10 mg orally once daily continuously) were evaluated in the phase I portion of this study to determine the maximum tolerated dose of everolimus to be used in the phase II study. RESULTS: Twenty-seven patients (9 acute myelogenous leukemia, 5 myelodysplastic syndrome, 6 B-chronic lymphocytic leukemia, 4 mantle cell lymphoma, 1 myelofibrosis, 1 natural killer cell/T-cell leukemia, and 1 T-cell prolymphocytic leukemia) received everolimus. No dose-limiting toxicities were observed. Grade 3 potentially drug-related toxicities included hyperglycemia (22%), hypophosphatemia (7%), fatigue (7%), anorexia (4%), and diarrhea (4%). One patient developed a cutaneous leukocytoclastic vasculitis requiring a skin graft. One patient with refractory anemia with excess blasts achieved a major platelet response of over 3-month duration. A second patient with refractory anemia with excess blasts showed a minor platelet response of 25-day duration. Phosphorylation of downstream targets of mTOR, eukaryotic initiation factor 4E-binding protein 1, and/or, p70 S6 kinase, was inhibited in six of nine patient samples, including those from the patient with a major platelet response. CONCLUSIONS: Everolimus is well tolerated at a daily dose of 10 mg daily and may have activity in patients with myelodysplastic syndrome. Studies of everolimus in combination with therapeutic agents directed against other components of the phosphatidylinositol 3-kinase/Akt/mTOR pathway are warranted.