Phase III vehicle-controlled, multi-centered study of topical alitretinoin gel 0.1% in cutaneous AIDS-related Kaposi's sarcoma. A randomized prospective trial of radiation therapy for AIDS-associated Kaposi's sarcoma. Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial.
This randomized, double-blind and vehicle-controlled phase III study was conducted to evaluate the efficacy and safety of alitretinoin gel 0.1% for the topical treatment of the cutaneous lesions of AIDS-related Kaposi's sarcoma (KS).
                Patients received treatment with alitretinoin gel (n = 62) or vehicle gel (n = 72) twice daily for 12 weeks. The primary efficacy endpoint was the cutaneous KS tumor response rate according to AIDS Clinical Trials Group (ACTG) objective criteria applied to topical therapy, with the patient as the unit of analysis.
                Treatment of patients with alitretinoin gel resulted in a significant antitumor effect. The overall patient response rate (complete plus partial response) was 37% (23 of 62) for the alitretinoin-treated patients and 7% (5 of 72) for the vehicle-treated patients (p = 0.00003). The difference in response rates for the 2 treatment groups remained significant even after taking into consideration numerous variables, including age (p = 0.00001), Eastern Cooperative Oncology Group (ECOG) status (p = 0.00002), CD4+ cell count (p = 0.00002), history of opportunistic infection (p = 0.00002), aggregate area of indicator lesions (p = 0.00005), number of raised indicator lesions (p = 0.00002), prior therapy for KS (p = 0.00003), and number of drugs (p = 0.00002) used in concomitant antiretroviral therapy. Generally, treatment with alitretinoin gel was well tolerated. The overall incidence of adverse events was similar for the 2 treatment groups. Adverse events related to treatment with alitretinoin gel tended to be mild to moderate in severity and limited to the site of application. The most frequent adverse event occurring at the application site following alitretinoin gel treatment was irritation coded as rash (32%).
                The results of this study provide convincing evidence of the superiority of alitretinoin gel over vehicle gel for the treatment of the cutaneous lesions of AIDS-related KS. The optimal dose of radiation in the treatment of AIDS-associated Kaposi's sarcoma has been controversial based on previous nonrandomized retrospective studies.
                Seventy-one cutaneous AIDS-associated Kaposi's sarcoma lesions were randomly assigned to 1 of 3 radiation dose regimens--8 Gy in 1 fraction, 20 Gy in 10 fractions, and 40 Gy in 20 fractions. Lesions were measured prior to and following treatment. Complete resolution of palpable tumor was considered a complete response, regardless of residual purple pigmentation. Reduction in palpable tumor to less than 50% of pretreatment area was considered an objective response. Less than 50% reduction in tumor size was considered a nonresponse.
                Complete response was higher (p = .04) with 40 Gy (83%) and 20 Gy (79%) than with 8 Gy (50%). Absence of residual purple pigmentation was greater (p = .005) with 40 Gy (43%) than with 20 Gy (8%) or 8 Gy (8%). Lesion failure was lower (p = .03) with 40 Gy (52%) than with 20 Gy (67%) or 8 Gy (88%). Median time to failure was 43 weeks with 40 Gy, 26 weeks with 20 Gy, and 13 weeks with 8 Gy (p = .003).
                Fractionated radiotherapy to higher total doses resulted in improved response and control of cutaneous Kaposi's sarcoma. This dose-dependence should be considered in determining the optimal radiotherapeutic regimen for individual patients treated for epidemic Kaposi's sarcoma. Kaposi's sarcoma (KS), the most common neoplasm in patients with AIDS, is a significant clinical problem for which current therapies are frequently unsatisfactory. We conducted a randomized phase III clinical trial to compare the efficacy and toxicities of a new form of therapy, pegylated-liposomal doxorubicin, with standard combination chemotherapy in patients with advanced AIDS-related KS (AIDS-KS).
                Two hundred fifty-eight patients with advanced AIDS-KS were randomly assigned to receive either pegylated-liposomal doxorubicin (20 mg/m2) or the combination of doxorubicin (20 mg/m2), bleomycin (10 mg/m2) and vincristine (1 mg) (ABV) every 14 days for six cycles. Standard response criteria, toxicity criteria, and predefined indicators of clinical benefit were examined to evaluate outcomes.
                Among 133 patients randomized to receive pegylated-liposomal doxorubicin, one achieved a complete clinical response and 60 achieved a partial response for an overall response rate of 45.9% (95% confidence interval [CI], 37% to 54%). Among 125 patients randomized to receive ABV, 31 achieved a partial response (24.8%; 95% confidence interval [CI], 17% to 32%). This difference was statistically significant (P < .001). In addition to objective responses, prospectively defined clinical benefits and toxicity outcomes also favored pegylated-liposomal doxorubicin.
                Pegylated-liposomal doxorubicin is more effective and less toxic than the standard combination chemotherapy regimen ABV for treatment of AIDS-KS.
Alitretinoin gel is effective in treating cutaneous KS, PLD is effective treatment for advanced KS and radiotherapy appears effective in treating cutaneous lesions. Apart from the trial of radiotherapy no trials applicable to developing settings were identified.