Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Activity of paclitaxel (Taxol) as therapy for HIV-associated Kaposi's sarcoma (KS) (Meeting abstract).
Proc Annu Meet Am Assoc Cancer Res; 14:A826 1995. Unique Identifier : AIDSLINE ICDB/95613978 Saville MW; Lietzau J; Pluda JM; Wilson W; Cohen R; Feigal E; Feuerstein I; Humphrey R; Broder S; Yarchoan R; National Cancer Institute, Bethesda, MD 20892
Abstract:
Inhibitors of microtubule assembly such as the vinca alkaloids are known to be clinically active against KS, and this led us to consider paclitaxel, an agent that stabilizes microtubule polymers, as a potential therapy. Paclitaxel was found to be cytostatic in KS-derived spindle cell lines at concentrations of less than 10 nM in vitro. With this background, we initiated a trial of paclitaxel 135 mg/m2 administered as a 3-hr IV infusion, with dose escalation each cycle as tolerated to a maximum of 175 mg/m2. Patients could have a maximum of one prior course of cytotoxic chemotherapy, and patients with visceral disease were eligible (unless immediately life-threatening). Twenty-four patients have been entered to date, most with severe immunosuppression (median CD4 count of 15 cells/mm3) and advanced KS (17 patients with tumor stage T1 and 6 with visceral disease). Of the 20 subjects currently evaluable, 10 (50%) have achieved a partial response, 9 have had minor responses or stable disease, and 1 has had progression. No patient has attained a complete remission to date. Of note, 3 of 5 patients with pulmonary KS had a partial response of their lung disease. Response durability off therapy has been short (approximately 2 months to progression), but each of two patients who have been retreated with the same regimen have again responded. Paclitaxel has been relatively well tolerated, with neutropenia being dose-limiting. Newly reported toxicities include a delayed urticarial skin rash in four patients, activation of preexisting psoriasis in one patient, fever to 40 C 17-20 days after infusion in two patients, and eosinophilia in 7 patients (unassociated with detectable plasma interleukin-4, -5, or GMCSF). These preliminary results suggest that paclitaxel has substantial activity in HlV-associated KS and may be a useful therapeutic agent. Further studies employing G-CSF, longer durations of infusion, drug combinations, and approaches to improve response durability should be considered.
Keywords: CD4 Lymphocyte Count Follow-Up Studies Human HIV Infections/*COMPLICATIONS/IMMUNOLOGY Neoplasm Staging Paclitaxel/ADVERSE EFFECTS/*THERAPEUTIC USE Sarcoma, Kaposi's/*DRUG THERAPY/*ETIOLOGY/IMMUNOLOGY/PATHOLOGY Time Factors ABSTRACT CLINICAL TRIAL 951230
M95C3222
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Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
