Alitretinoin (original) (raw)

Abstract

▴ Alitretinoin is a retinoid receptor pan-agonist, which has been investigated in the treatment of Kaposi’s sarcoma (KS). Binding with high affinity to all known retinoid receptors, alitretinoin is thought to regulate proliferation, differentiation, and apoptosis of KS cells.

▴ Significantly more patients experienced complete or partial responses [according to the AIDS Clinical Trials Group (ACTG) criteria for topical treatment of cutaneous KS] with alitretinoin 0.1% gel 2 to 4 times daily than with vehicle gel in 2 phase III, multicenter, 12-week, randomized, double-blind clinical trials of patients with AIDS-related KS (35 vs 18%, p = 0.002 and 37 vs 7%, p = 0.00003, respectively). Responses were also observed in patients refractory to prior systemic or topical anti-KS therapies.

▴ In an intent-to-treat analysis in a phase II trial, 37% of patients with AIDS-related KS receiving alitretinoin capsules 60 to 100 mg/m2/day demonstrated either complete or partial responses (determined by ACTG criteria).

▴ The majority of adverse events associated with alitretinoin 0.1% gel were classified as either mild or moderate, occurred at the site of application and were reversible. In both phase III trials, rash was the most common adverse event.

▴ The most common adverse events in patients taking alitretinoin capsules included headache, dry skin, rash, alopecia, exfoliative dermatitis, and hyperlipidemia.

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References

  1. Antman K., Chang Y. Kaposi’ sarcoma. N Engl J Med 2000 Apr 6; 342 (14): 1027–1038
    Article PubMed CAS Google Scholar
  2. Clark-Loeser L., Friedman-Kien A., Washenik K. Alitretinoin gel for the topical treatment of AIDS-related Kaposi’ sarcoma. Today’ Therapeutic Trends 1999; 17 (4): 289–302
    Google Scholar
  3. Redfern C.P.F., Lovat P.E., Malcolm A.J., et al. Gene expression and neuroblastoma cell differentiation in response to retinoic acid: differential effects of 9-cis and all-trans retinoic acid. Eur J Cancer 1995; 31A (4): 486–494
    Article PubMed CAS Google Scholar
  4. Brodowicz T., Wiltschke C., Kandioler-Eckersberger D., et al. Inhibition of proliferation and induction of apoptosis in soft tissue sarcoma cells by interferon-α and retinoids. Br J Cancer 1999 Jul; 80 (9): 1350–1358
    Article PubMed CAS Google Scholar
  5. Duvic M., Chandraratna R.A.S. Retinoid receptor selectivity: importance and clinical application in skin diseases and other diseases. Dermatologic Therapy 1998; 7: 7–14
    Google Scholar
  6. Gottardis M.M., Lamph W.W., Shalinsky D.R., et al. The efficacy of 9-cis retinoic acid in experimental models of cancer. Breast Cancer Res Treat 1996; 38: 85–96
    Article PubMed CAS Google Scholar
  7. Willy P., Umesono K., Ong E., et al. Lxr, a nuclear receptor that defines a distinct response pathway. Genes Dev 1995; 9: 1033–1045
    Article PubMed CAS Google Scholar
  8. Zhang X., Lehmann J., Hoffmann B., et al. Homodimer formation of retinoid X-receptor induced by 9-_cis_-retinoic acid. Nature 1992; 358: 587–591
    Article PubMed CAS Google Scholar
  9. Lovat P.E., Lowis S.P., Pearson A.D.J., et al. Concentration-dependent effects of 9-cis retinoic acid on neuroblastoma differentiation and proliferation in vitro. Neurosci Lett 1994 Nov 21; 182: 29–32
    Article PubMed CAS Google Scholar
  10. Lovat P.E., Irving H., Annicchiarico-Petruzzelli M., et al. Retinoids in neuroblastoma therapy: distinct biological properties of 9-_cis_- and all-_trans_-retinoic acid. Eur J Cancer 1997 Oct; 33: 2075–2080
    Article PubMed CAS Google Scholar
  11. Ligand Pharmaceuticals Panretin® (alitretinoin) prescribing information. Ligand Pharmaceuticals, USA, 2000. Available from: http://www.ligand.com [Accessed 2000 Jun 19]
    Google Scholar
  12. Miller V.A., Rigas J.R., Benedetti F.M., et al. Initial clinical trial of the retinoid receptor pan agonist 9-cis retinoic acid. Clin Cancer Res 1996 Mar; 2: 471–475
    PubMed CAS Google Scholar
  13. Weber C., Dumont E. Pharmacokinetics and pharmacodynamics of 9-_cis_-retinoic acid in healthy men. J Clin Pharmacol 1997 Jul; 37: 566–574
    PubMed CAS Google Scholar
  14. Rizvi N.A., Marshall J.L., Ness E., et al. Phase I study of 9-_cis_-retinoic acid (ALRT1057 capsules) in adults with advanced cancer. Clin Cancer Res 1998 Jun; 4: 1437–1442
    PubMed CAS Google Scholar
  15. Sass.O., Masgrau E., Saurat J.-H., et al. Metabolism of oral 9-_cis_-retinoic acid in the human: identification of 9-_cis_-retinoyl-ß-glucuronide and 9-_cis_-4-oxo-retinoyl- ß-glucuronide as urinary metabolites. Drug Metab and Dispos 1995 Sep; 23: 887–891
    CAS Google Scholar
  16. Duvic M., Friedman-Kien A.E., Miles S.A., et al. Phase I–II evaluation of Panretin™ (ALRT1057; LGD1057; AGN192013; 9-_cis_-retinoic acid) topical gel for AIDSrelated cutaneous Kaposi’ sarcoma [abstract no. 160]. 33rd Annual Meeting Am Soc Clin Oncol; 1997 May 17–20; Denver, 46
    Google Scholar
  17. Walmsley S., Northfelt D.W., Melosky B., et al. Treatment of AIDS-related cutaneous Kaposi’ sarcoma with topical alitretinoin (9-_cis_-retinoic acid) gel. J Acquir Immune Defic Syndr 1999 Nov 1; 22: 235–246
    PubMed CAS Google Scholar
  18. Bodsworth N., International Panretin® Gel KS Study Group. Topical 9-_cis_-retinoic acid (Panretin®) gel as treatment of cutaneous AIDS-related Kaposi’ sarcoma: interim results of an international, placebo-controlled trial (ALRT 1057-503) [abstract/poster presentation]. 12th World AIDS Conference; 1998 Jun 28–Jul 3; Geneva, 317–318
    Google Scholar
  19. Miles S.A., Dezube B.J., Saville W., et al. Oral 9-_cis_-retinoic acid (panretin, LGD1057) is active in AIDS-related Kaposi’ sarcoma: AIDS Malignancy Consortium Study #002 [abstract no. 45]. Chemother Symp; 1998 Nov 11–13; New York, 53
    Google Scholar
  20. Miles S, Dezube B., Lee J., et al. Anti-tumor activity of oral 9-_cis_-retinoic acid in AIDS related Kaposi’ sarcoma: AIDS Malignancy Consortium Study 002 [abstract no. 22276]. 12th World AIDS Conference; 1998 Jun 28–Jul 3; Geneva, 317
    Google Scholar
  21. Friedman-Kien A., Conant M. Phase 2 study (Protocol L1057-28) of Panretin? capsules (LGD1057, ALRT1057) for AIDS-related Kaposi’ sarcoma [abstract no. 22278]. 12th World AIDS Conference; 1998 Jun 28–Jul 3; Geneva, 318
    Google Scholar
  22. Tompkins C., Kean Y., Yocum R. Efficacy and safety of long-term alitretinoin gel (Panretin®) for cutaneous AIDS-related Kaposi’ sarcoma [abstract A22]. J Acquir Immune Defic Syndr 2000; 23 (3): A22
    Google Scholar
  23. Duvic M., Friedman-Kien A.E., Galpin J., et al. Phase I–II clinical trial supports safety and efficacy of ALRT 1057 topical retinoid gel for Kaposi’ sarcoma [abstract no. Mo.B.432]. 11th International Conference on AIDS; 1996 Jul 7–12; Vancouver, 27
    Google Scholar
  24. Conant M. Topical alitretinoin gel as treatment for cutaneous lesions of AIDS-related Kaposi’ sarcoma: results of multicenter, double-blind, vehicle-controlled trials [abstract no. 205]. 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago, 205
    Google Scholar
  25. US Food and Drug Administration Panretin alitretinoin gel approval/ reviewer information [online]. US Food and Drug Administration, 1999 June 16. Available from: http://www.fda.gov/cder/approval/index.htm [Accessed 2000 Jun 13] ai]26._Aboulafia D.M., Bundow D., Weaver C., et al. Retinoid-induced hypercalcemia in a patient with Kaposi sarcoma associated with acquired immunodeficiency syndrome. Am J Clin Oncol 1998 Oct; 21 (5): 513–517
    Google Scholar
  26. Aboulafia DM, Bundow D, Weaver C, et al. Retinoid-induced hypercalcemia in a patient with Kaposi sarcoma associated with acquired immunodeficiency syndrome. Am J Clin Oncol 1998 Oct; 21(5): 513–7
    Article PubMed CAS Google Scholar

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  1. Adis International Limited, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand
    Susan M. Cheer & Rachel H. Foster

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  1. Susan M. Cheer
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  2. Rachel H. Foster
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Correspondence toSusan M. Cheer.

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Cheer, S.M., Foster, R.H. Alitretinoin.Am J Clin Dermatol 1, 307–314 (2000). https://doi.org/10.2165/00128071-200001050-00005

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