Interferon and Cancer

Interferon is an effective treatment for erythrocytosis.

Cancer. 2007 Sep 11; [Epub ahead of print] Links
PEG-IFN-alpha-2b therapy in BCR-ABL-negative myeloproliferative
disorders: final Result of a Phase 2 Study.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.

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
mug/kg/wk for the first 14 patients and then 2 mug/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.
Cancer 2007. (c) 2007 American Cancer Society.

PMID: 17849460 [PubMed - as supplied by publisher]
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interferon-alpha inhibits erythropoiesis
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Exp Hematol. 1995 Nov;23(12):1310-8. Related Articles, Links


Interferon-alpha-induced apoptosis in human erythroid progenitors.


Tarumi T, Sawada K, Sato N, Kobayashi S, Takano H, Yasukouchi T,
Takashashi T, Sekiguchi S, Koike T.


Department of Internal Medicine II, Hokkaido University School of
Department of Internal Medicine II, Hokkaido University School of
Medicine, Japan.


Recombinant human interferon-alpha (rIFN-alpha) inhibits
erythropoiesis, in vivo and in vitro. In an attempt to clarify
mechanisms related to this inhibition, effects of rIFN-alpha on
highly
purified human peripheral blood burst-forming units-erythroid (BFU-E)
(20-60% purity) were compared with effects on erythroid progenitors
in
various stages of development. Day-1 and -7 cultured cells were
equivalent to primitive BFU-E and colony-forming units-erythroid
(CFU-E), respectively. Day-1 BFU-E supported by recombinant human
erythropoietin (rEpo) and interleukin-3 (rIL-3) was inhibited by
rIFN-alpha in a dose-dependent manner, and a significant inhibition
occurred at 2000 U/mL rIFN-alpha. Limiting dilution analysis
demonstrated that rIFN-alpha directly inhibits BFU-E rIFN-alpha
inhibited the proliferative capacity or the colony expression of
erythroid progenitors, with no relation to the stage of development,
but inhibition of differentiation was not apparent. This evidence
suggested that apoptosis of erythroid progenitors was induced by
IFN-alpha. When day-7 cells were incubated with IFN-alpha in the
presence of rEpo, there was an increased breakdown of total cellular
DNA into DNA fragments of less than 5 kb; hence, the inhibitory
effect
of IFN-alpha on erythroid progenitors may mediate apoptosis.


PMID: 7589287 [PubMed - indexed for MEDLINE]


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