Abstract:
KS is a frequent cause of severe morbidity and death in patients with human immunodeficiency virus (HIV) infection. Current therapies are often poorly tolerated, and new drugs are needed for this condition. It has been observed that inhibitors of microtubule assembly are active against KS, and this led us to consider paclitaxel, an agent that causes microtubule polymerization, as a potential therapy for this disorder. In in vitro studies, we found that paclitaxel inhibited the proliferation of a KS-derived spindle cell line at a concentration of approximately 10 nM. As a prelude to conducting a formal Phase II study, we treated three KS pts with 105 mg/m2 paclitaxel by continuous 96 hr infusion every 21 days. Toxicity consisted of moderate myelosuppression, alopecia, one acute skin rash, and four episodes of central venous catheter infection. Each of two evaluable pts, including one with pulmonary involvement, achieved a partial response (PR). We subsequently initiated a Phase II trial of paclitaxel 135 mg/m2, administered as a 3 hour infusion by peripheral catheter, with dose escalation each cycle as tolerated to a maximum of 155 mg/m2. The 3 hour infusion schedule was chosen as being more practical than a 96-hr infusion, and to avoid the problem of line infections associated with an indwelling catheter. Patients entered on this study could have had a maximum of one prior course of cytotoxic chemotherapy, and could have visceral disease which was not immediately life-threatening. Six patients have been entered to date. Despite limited follow up (average 2.6 cycles of treatment), one patient has attained a PR and none have had progression. Two patients developed a skin rash 10 days after treatment, and one developed fever, malaise, and thrombocytopenia 18-24 days after treatment for two consecutive cycles. Otherwise, myelosuppression has been brief and not associated with infection. Updated results will be presented.
Keywords: Cell Division/DRUG EFFECTS Dose-Response Relationship, Drug Follow-Up Studies Human HIV Infections/*DRUG THERAPY/PATHOLOGY Infusions, Intravenous Paclitaxel/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS Sarcoma, Kaposi's/*DRUG THERAPY/PATHOLOGY Skin Neoplasms/*DRUG THERAPY/PATHOLOGY ABSTRACT CLINICAL TRIAL CLINICAL TRIAL, PHASE II
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