Results of a Randomized Study of IM862 Nasal Solution in the Treatment of AIDS-Related Kaposi’s Sarcoma

Abstract

IM862 given as intranasal drops is well tolerated and has antitumor activity in patients with AIDS-KS. A randomized double-blinded study to define the activity of IM862 in patients with AIDS-KS is in progress.

Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma

“…Furthermore, a demonstrated activity of IM862 in AIDSrelated Kaposi's sarcoma (Tulpule et al, 2000) together with minimal toxicity, especially with regard to the many side effects encountered with IL-2 and IFNa, prompted us to initiate this phase II trial. We were able to confirm, like others (Tulpule et al, 2000;Garcia et al, 2001), the lack of significant toxicity of IM862. We did not observe any objective response.…”

“…First, the dosing and schedule used could be inadequate and we had no way to evaluate if therapeutically active concentrations of IM862 had been reached, such as by measuring IM862 blood levels or modulation of Th1 lymphocyte subset. However, Tulpule et al (2000) used a lower dose of 5 mg given intranasally once daily every other day or for 5 days, followed by 5 days of rest. For this lower concentration, a demonstrable clinical effect was recorded in terms of response rate.…”

“…Therefore, to achieve an objective response with an antiangiogenic compound does not seem unrealistic, and the fact that Tulpule et al (2000) reported objective responses in Kaposi's sarcoma with IM862 initially prompted us to choose response rate as the primary objective in our study. But, as already mentioned earlier, we allowed for SD to account as a clinical benefit in the design of our trial, thus anticipating a potential effect other than tumour shrinkage.…”

“…The rationale for using IM862 was its known immunomodulatory and antiangiogenic properties, making this compound a good candidate for treatment of a highly vascularised tumour responsive to immunotherapy. Furthermore, a demonstrated activity of IM862 in AIDSrelated Kaposi's sarcoma (Tulpule et al, 2000) together with minimal toxicity, especially with regard to the many side effects encountered with IL-2 and IFNa, prompted us to initiate this phase II trial. We were able to confirm, like others (Tulpule et al, 2000;Garcia et al, 2001), the lack of significant toxicity of IM862.…”

“…IM862 has also been shown to be a potent antiangiogenic agent both in vitro and in vivo (IM862 Investigator 's Brochure, 1998;Ferrario et al, 2000). A significant anticancer activity has been reported recently in AIDSrelated Kaposi's sarcoma, a tumour of endothelial cell origin (Tulpule et al, 2000). Responses have also been documented in ovarian carcinoma and skin melanoma (Garcia et al, 2001).…”