Topical treatment of cutaneous lesions of acquired immunodeficiency syndrome-related Kaposi sarcoma using alitretinoin gel: results of phase 1 and 2 trials

Arch Dermatol. 2000 Dec;136(12):1461-9. doi: 10.1001/archderm.136.12.1461.

Abstract

Objective: To evaluate the efficacy and safety of topical alitretinoin gel (9-cis-retinoic acid [LGD1057], Panretin gel; Ligand Pharmaceuticals, Inc, San Diego, Calif) in cutaneous Kaposi sarcoma (KS).

Design: Open-label, within-patient, controlled, dose-escalating phase 1 and 2 clinical trials. In all patients, 1 or more cutaneous KS lesions were treated with alitretinoin gel, and at least 2 other lesions served as untreated controls for up to 16 weeks. Alitretinoin (0.05% or 0.1% gel) was applied twice daily for the first 2 weeks and up to 4 times daily thereafter, if tolerated.

Setting: Nine academic clinical centers.

Patients: One hundred fifteen patients with biopsy-proven acquired immunodeficiency syndrome (AIDS)-related KS.

Main outcome measures: AIDS Clinical Trials Group response criteria.

Results: Statistically significant clinical responses were observed in 31 (27%) of 115 patients for the group of treated index lesions compared with 13 (11%) for the group of untreated control lesions (P<.001). Responses occurred with low CD4(+) lymphocyte counts (<200 cells/microL) and in some patients with refractory response to previous systemic anti-KS therapy. The incidence of disease progression was significantly lower for treated index lesions compared with untreated control lesions (39/115 [34%] vs 53/115 [46%]; P =.02). Alitretinoin gel generally was well tolerated, with 90% of treatment-related adverse events confined to the application site and only mild or moderate in severity.

Conclusions: Alitretinoin gel has significant antitumor activity as a topical treatment for AIDS-related KS lesions, substantially reduces the incidence of disease progression in treated lesions, and is generally well tolerated.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / pathology
  • Administration, Cutaneous
  • Adult
  • Alitretinoin
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Gels
  • Humans
  • Male
  • Middle Aged
  • Sarcoma, Kaposi / drug therapy*
  • Sarcoma, Kaposi / pathology
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Treatment Outcome
  • Tretinoin / administration & dosage
  • Tretinoin / therapeutic use*
  • United States

Substances

  • Antineoplastic Agents
  • Gels
  • Alitretinoin
  • Tretinoin