All-trans retinoic acid (ATRA) in patients with chronic myeloid leukemia in the chronic phase

D. Russo, M. Regazzi, S. Sacchi, G. Visani, M. Lazzarino, G. Avvisati, P. G. Pelicci, G. Dastoli, C. Grandi, I. Iacona, A. Candoni, R. Grattoni, P. Galieni, S. Rupoli, A. M. Liberati, A. T. Maiolo

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Since in vitro observations indicated that all-trans retinoic acid (ATRA), especially in combination with IFNα, can exert significant suppressive effects on Ph+ cells, we investigated the effects and the pharmacokinetic profile of ATRA in a selected cohort of patients with Ph+ chronic myeloid leukemia (CML) in chronic phase. Eighteen patients were treated with ATRA at a dose of 80 mg/m2/day (p.o.), divided into two equal doses after meals, for 7 consecutive days every other week for a maximum of 12 courses (1 course = 1 week on and 1 week off). Pharmacokinetic profiles of ATRA were evaluated during intermittent therapy on days 1 and 7 of course 1; on day 1 of course 2; on day 1 of course 6. Out of the 18 patients treated with ATRA, 11 (61%) went off study before the sixth course of treatment because of progressive hyperleukocytosis (seven cases), or thrombocytosis (one case), or refusal (three cases). Seven (39%) patients completed the first six courses (12 weeks) of treatment with ATRA and two of them (11%) maintained a white blood cell (WBC) <10 x 109/l which was induced by the pretreatment with hydroxyurea. One patient completed the 12th course of ATRA maintaining WBC <10 x 109/l, platelets <500 x 109/l and spleen not palpable. The treatment with ATRA was well tolerated and only one patient discontinued the therapy because of non-hematological side-effects. The area under the concentration-time curve (AUC) decreased significantly (P <0.001) during the first week of therapy. By adopting an intermittent dosing regimen, 1 week on/1 week off (1 course), at the start of courses 2 and 6, we obtained the ATRA AUCs equivalent to the ones achieved on day 1 of course 1. In conclusion, our results showed that ATRA alone appeared to be unable to control the WBC expansion in the CML patients in chronic phase. Moreover, it did not induce any remarkable cytoreductive effects on the platelet count and on the hemoglobin level. The major interest of ATRA would be in combination with other therapies. If ATRA was given in combination with IFNα or other agents, dose reduction of these would not be planned. On the basis of the pharmacokinetic profile, ATRA should be administered intermittently rather than continuously.

Original languageEnglish
Pages (from-to)449-454
Number of pages6
JournalLeukemia
Volume12
Issue number4
DOIs
Publication statusPublished - 1998

Fingerprint

Leukemia, Myeloid, Chronic Phase
Tretinoin
Leukocytes
Pharmacokinetics
Therapeutics
Thrombocytosis
Hydroxyurea
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Platelet Count
Area Under Curve

Keywords

  • ATRA
  • CML
  • Pharmacokinetics
  • Therapy

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Russo, D., Regazzi, M., Sacchi, S., Visani, G., Lazzarino, M., Avvisati, G., ... Maiolo, A. T. (1998). All-trans retinoic acid (ATRA) in patients with chronic myeloid leukemia in the chronic phase. Leukemia, 12(4), 449-454. https://doi.org/10.1038/sj.leu.2400988

All-trans retinoic acid (ATRA) in patients with chronic myeloid leukemia in the chronic phase. / Russo, D.; Regazzi, M.; Sacchi, S.; Visani, G.; Lazzarino, M.; Avvisati, G.; Pelicci, P. G.; Dastoli, G.; Grandi, C.; Iacona, I.; Candoni, A.; Grattoni, R.; Galieni, P.; Rupoli, S.; Liberati, A. M.; Maiolo, A. T.

In: Leukemia, Vol. 12, No. 4, 1998, p. 449-454.

Research output: Contribution to journalArticle

Russo, D, Regazzi, M, Sacchi, S, Visani, G, Lazzarino, M, Avvisati, G, Pelicci, PG, Dastoli, G, Grandi, C, Iacona, I, Candoni, A, Grattoni, R, Galieni, P, Rupoli, S, Liberati, AM & Maiolo, AT 1998, 'All-trans retinoic acid (ATRA) in patients with chronic myeloid leukemia in the chronic phase', Leukemia, vol. 12, no. 4, pp. 449-454. https://doi.org/10.1038/sj.leu.2400988
Russo, D. ; Regazzi, M. ; Sacchi, S. ; Visani, G. ; Lazzarino, M. ; Avvisati, G. ; Pelicci, P. G. ; Dastoli, G. ; Grandi, C. ; Iacona, I. ; Candoni, A. ; Grattoni, R. ; Galieni, P. ; Rupoli, S. ; Liberati, A. M. ; Maiolo, A. T. / All-trans retinoic acid (ATRA) in patients with chronic myeloid leukemia in the chronic phase. In: Leukemia. 1998 ; Vol. 12, No. 4. pp. 449-454.
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AU - Maiolo, A. T.

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