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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 Sézary syndrome).

Publication ,  Journal Article
Dummer, R; Duvic, M; Scarisbrick, J; Olsen, EA; Rozati, S; Eggmann, N; Goldinger, SM; Hutchinson, K; Geskin, L; Illidge, TM; Giuliano, E ...
Published in: Ann Oncol
September 2014

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.

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Published In

Ann Oncol

DOI

EISSN

1569-8041

Publication Date

September 2014

Volume

25

Issue

9

Start / End Page

1807 / 1812

Location

England

Related Subject Headings

  • Treatment Failure
  • Skin Neoplasms
  • Sezary Syndrome
  • Pyrimidinones
  • Purine-Nucleoside Phosphorylase
  • Purine Nucleosides
  • Oncology & Carcinogenesis
  • Mycosis Fungoides
  • Middle Aged
  • Male
 

Citation

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Dummer, R., Duvic, M., Scarisbrick, J., Olsen, E. A., Rozati, S., Eggmann, N., … Kim, Y. H. (2014). 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 Sézary syndrome). Ann Oncol, 25(9), 1807–1812. https://doi.org/10.1093/annonc/mdu231
Dummer, R., M. Duvic, J. Scarisbrick, E. A. Olsen, S. Rozati, N. Eggmann, S. M. Goldinger, et al. “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 Sézary syndrome).Ann Oncol 25, no. 9 (September 2014): 1807–12. https://doi.org/10.1093/annonc/mdu231.
Dummer R, Duvic M, Scarisbrick J, Olsen EA, Rozati S, Eggmann N, Goldinger SM, Hutchinson K, Geskin L, Illidge TM, Giuliano E, Elder J, Kim YH. 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 Sézary syndrome). Ann Oncol. 2014 Sep;25(9):1807–1812.
Journal cover image

Published In

Ann Oncol

DOI

EISSN

1569-8041

Publication Date

September 2014

Volume

25

Issue

9

Start / End Page

1807 / 1812

Location

England

Related Subject Headings

  • Treatment Failure
  • Skin Neoplasms
  • Sezary Syndrome
  • Pyrimidinones
  • Purine-Nucleoside Phosphorylase
  • Purine Nucleosides
  • Oncology & Carcinogenesis
  • Mycosis Fungoides
  • Middle Aged
  • Male