Gemcitabine

Gemcitabine is a novel pyrimidine antimetabolite with clinical activity and a low-toxicity profile in solid tumors and selected T-cell hematologic malignancies. A phase II study involving 44 previously treated patients with either MF (n = 30) or PTCL with exclusive skin involvement (n = 14) treated with gemcitabine reported 5 (11.5%) CRs and 26 (59%) PRs, for an overall response rate of 70.5%.117 Responses varied by histology: three of 30 (10%) MF patients attained a CR and 18 of 30 (60%) had PRs, while two of 14 (14.5%) PTCL patients had CRs and eight of 14 (57%) achieved PRs. The median duration of CR was 15 months (range 6-22 months) and of PR was 10 months (range 2-15 months). Treatment was generally well tolerated, and hematologic toxicities were mild. Gemcitabine was also found to be effective and well-tolerated therapy for relapsed or refractory T-cell malignancies in another study involving 10 patients with various histologies.118 There were 2 CRs and 4 PRs, for an overall response rate of 60%, with a median duration of response of 13.5 months.

A pivotal, multicenter phase III trial was then performed to evaluate the activity of denileukin diftitox in patients with CD25+ CTCL.119 Patients were randomized to receive denileukin diftitox given at a dose of either 9 ^g/kg/day for 5 days every 3 weeks or 18 ^g/kg/day for 5 days every 3 weeks, with no steroid premedication. Thirteen of 36 patients receiving the higher dose had an objective response, as compared to eight of 35 patients in the lower dose cohort. Overall, 20% of patients had PRs while 10% had CRs, with the mean duration of response being 6.9 months. There were CRs in both groups, with the 3 CRs in the lower dose group having early stage (IB) disease, while the 3 CRs in the higher dose group had stage IIB or higher disease, suggesting a role for the higher dose in patients with advanced-stage disease (Table 60.4). An increase in the titer of antidenileukin diftitox antibodies was seen in most patients, which did not have a significant effect on antitumor efficacy. Regarding tumor CD25 status, 58% of all skin samples of CTCL patients met the inclusion criteria of having greater than 20% CD25 positivity on tumor cell surface. However, in multiple instances, the results from multiple biopsies taken from the same patient showed a wide range of CD25 expression. Side effects included acute hyper-sensitivity-type events related to drug administration, associated with dypsnea, back pain, hypotension, chest tightness, pruritus, and flushing. Transient elevation of liver enzymes was also seen, as well as rashes and

60.4 Denileukin diftitox in cutaneous T-cell lymphoma—results from pivotal phase III trial119

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60.4 Denileukin diftitox in cutaneous T-cell lymphoma—results from pivotal phase III trial119

DAB389IL-2 dose

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Back Pain Relief

Back Pain Relief

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