9-cis-retinoic acid capsules in the treatment of AIDS-related Kaposi sarcoma: results of a phase 2 multicenter clinical trial.
OBJECTIVE
To evaluate the safety, dose tolerance, and anti-tumor effects of 9-cis-retinoic acid in the treatment of Kaposi sarcoma (KS) related to acquired immunodeficiency syndrome (AIDS).


METHODS
Phase 2, open-label clinical trial of oral doses of 9-cis-retinoic acid increasing in 40-mg increments every 2 weeks from 60 mg/m(2) per day to a maximum of 140 mg/m( 2) per day.


METHODS
Five hospital or health maintenance organization outpatient clinics.


METHODS
Fifty-seven adult male patients with human immunodeficiency virus and biopsy-proven KS.


METHODS
Safety was evaluated by adverse events, physical examination, laboratory test abnormalities, treatment-limiting toxic effects, and reasons for early withdrawal. Response (>/=50% improvement) was evaluated by an overall KS response and by the area and height from 6 index lesions selected at baseline.


RESULTS
Patients tolerated 60 and 100 mg/m(2) per day. Most patients found 140 mg/m(2) per day intolerable owing to headache. Common treatment-related adverse events were headache, xerosis, rash, alopecia, and hyperlipemia. The patient response rate for the overall KS disease was 19% (11/57), including 1 patient with clinically complete response. The response rate assessed by measuring 6 index lesions during treatment was 39% (22/57). Sixteen responding patients (73%) were refractory to at least 1 previous anti-KS therapy. Patients with CD4( +) counts of 150 cells/ micro L or lower were as likely to respond as patients with counts of higher than 150 cells/ micro L. The median time to response was 8.5 weeks (range, 4.0-21.1 weeks). The median duration of treatment was 15.1 weeks (range, 0.14 to >/=62 weeks).


CONCLUSIONS
9-cis-retinoic acid capsules have moderate activity and provide durable responses, but substantial toxic effects at higher doses limit its suitability as an anti-KS therapy.
Aboulafia
David M
DM
Section of Hematology/Oncology, Virginia Mason Medical Center, 1100 Ninth Ave, PO Box 900 (H14-HEM), Seattle, WA 98111-0900, USA. hemdma@vmmc.org
Norris
Dorece
D
Henry
David
D
Grossman
Ronald J
RJ
Thommes
James
J
Bundow
Denise
D
Yocum
Richard C
RC
Stevens
Victor
V
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001707:Biopsy, Needle; D002214:Capsules; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D018570:Risk Assessment; D012514:Sarcoma, Kaposi / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016037:Single-Blind Method; D012878:Skin Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D002214:Capsules; D000077556:Alitretinoin; D014212:Tretinoin