PMID- 24948692 OWN - NLM STAT- MEDLINE DCOM- 20150608 LR - 20240229 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 25 IP - 9 DP - 2014 Sep TI - Final results of a multicenter phase II study of the purine nucleoside phosphorylase (PNP) inhibitor forodesine in patients with advanced cutaneous T-cell lymphomas (CTCL) (Mycosis fungoides and Sezary syndrome). PG - 1807-1812 LID - S0923-7534(19)35109-9 [pii] LID - 10.1093/annonc/mdu231 [doi] AB - BACKGROUND: Forodesine is a potent inhibitor of purine nucleoside phosphorylase (PNP) that leads to intracellular accumulation of deoxyguanosine triphosphate (dGTP) in T and B cells, resulting in apoptosis. Forodesine has demonstrated impressive antitumor activity in early phase clinical trials in cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: In this phase II study, patients with CTCL who had already failed three or more systemic therapies were recruited. We investigated the response rate, safety and tolerability of oral forodesine treatment in subjects with cutaneous manifestations of CTCL, stages IB, IIA, IIB, III and IVA. The safety population encompassing all stages was used for analysis of accountability, demographics and safety. The efficacy population differed from the safety population by exclusion of stage IB and IIA patients. RESULTS: All 144 patients had performance status 0-2. The median duration of CTCL from diagnosis was 53 months (5-516 months). The median number of pretreatments was 4 (range: 3-15). No complete remissions were observed. In the efficacy group of patients, 11% achieved partial remission and 50% had stable disease. The median time to response was 56 days and the median duration of response was 191 days. A total of 96% of all treated patients reported one or more adverse events (AEs) and 33% reported a serious AE. The majority of AEs were classified as mild or moderate in severity. The most commonly reported AEs (>10%) were peripheral edema, fatigue, insomnia, pruritus, diarrhea, headache and nausea. Overall eight patients died during the study: five due to sepsis and infections, one due to a second malignancy (esophageal cancer), one due to disease progression and one due to liver failure. CONCLUSION: Oral forodesine at a dose of 200 mg daily is feasible and shows partial efficacy in this highly selected CTCL population and some durable responses. CI - (c) The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Dummer, R AU - Dummer R AD - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. Electronic address: reinhard.dummer@usz.ch. FAU - Duvic, M AU - Duvic M AD - Department of Dermatology, MD Anderson Cancer Center, Houston, USA. FAU - Scarisbrick, J AU - Scarisbrick J AD - Department Dermatology, Hospital Birmingham, Birmingham, UK. FAU - Olsen, E A AU - Olsen EA AD - Department of Dermatology, Duke University Medical Center, Durham, USA. FAU - Rozati, S AU - Rozati S AD - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. FAU - Eggmann, N AU - Eggmann N AD - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. FAU - Goldinger, S M AU - Goldinger SM AD - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. FAU - Hutchinson, K AU - Hutchinson K AD - Clinical Research, AMS Ltd, London, UK. FAU - Geskin, L AU - Geskin L AD - Department of Dermatology, University of Pittsburgh, Pittsburgh, USA. FAU - Illidge, T M AU - Illidge TM AD - School of Cancer and Imaging Sciences, University of Manchester, Manchester, UK. FAU - Giuliano, E AU - Giuliano E AD - Clinical Development, BioCryst Pharmaceuticals, Inc., Durham. FAU - Elder, J AU - Elder J AD - Statistics, PharPoint Research, Inc., Chapel Hill. FAU - Kim, Y H AU - Kim YH AD - Clinical Research, Stanford Cancer Center, Stanford, USA. LA - eng SI - ClinicalTrials.gov/NCT00501735 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20140619 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Antineoplastic Agents) RN - 0 (Purine Nucleosides) RN - 0 (Pyrimidinones) RN - 426X066ELK (forodesine) RN - EC 2.4.2.1 (Purine-Nucleoside Phosphorylase) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Apoptosis/drug effects MH - Female MH - Humans MH - Male MH - Middle Aged MH - Mycosis Fungoides/*drug therapy MH - Purine Nucleosides/adverse effects/*therapeutic use MH - Purine-Nucleoside Phosphorylase/antagonists & inhibitors MH - Pyrimidinones/adverse effects/*therapeutic use MH - Sezary Syndrome/*drug therapy MH - Skin Neoplasms/*drug therapy MH - Treatment Failure OTO - NOTNLM OT - Sezary syndrome OT - cutaneous T-cell lymphomas OT - forodesine OT - mycosis fungoides OT - purine nucleoside phosphorylase inhibitor EDAT- 2014/06/21 06:00 MHDA- 2015/06/09 06:00 CRDT- 2014/06/21 06:00 PHST- 2014/06/21 06:00 [entrez] PHST- 2014/06/21 06:00 [pubmed] PHST- 2015/06/09 06:00 [medline] AID - S0923-7534(19)35109-9 [pii] AID - 10.1093/annonc/mdu231 [doi] PST - ppublish SO - Ann Oncol. 2014 Sep;25(9):1807-1812. doi: 10.1093/annonc/mdu231. Epub 2014 Jun 19.