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


METHODS
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.


METHODS
Nine academic clinical centers.


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


METHODS
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.
Duvic
M
M
Section of Dermatology, M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. mduvic@mdanderson.org
Friedman-Kien
A E
AE
Looney
D J
DJ
Miles
S A
SA
Myskowski
P L
PL
Scadden
D T
DT
Von Roenn
J
J
Galpin
J E
JE
Groopman
J
J
Loewen
G
G
Stevens
V
V
Truglia
J A
JA
Yocum
R C
RC
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000473:pathology; D000279:Administration, Cutaneous; D000328:Adult; D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005782:Gels; D006801:Humans; D008297:Male; D008875:Middle Aged; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000627:therapeutic use*; D014481:United States
D000970:Antineoplastic Agents; D005782:Gels; D000077556:Alitretinoin; D014212:Tretinoin