A phase II trial of interferon-alpha and XXXX in metastatic renal carcinoma: clinical and anti-angiogenic effects.

@entity1 @entity12698 @entity137 @entity7 @entity5 @entity1421 @entity540 @entity1358 @entity74 @entity4020 @entity3840
UNASSIGNED: 4604 Background: Interferon-alpha ( @entity4020 ) is a standard initial therapy in @entity1358 ( @entity1358 ) with anti- @entity5 effects via immunologic and anti-angiogenic mechanisms. @entity3840 ( @entity3840 ) is an enzyme involved in the formation of @entity1421 and may play a major role in development of @entity5 through numerous mechanisms, including neovascularization. @entity3840 is expressed in the majority of @entity1358 and correlates with stage, grade and microvessel density. Based on potential additive or synergistic anti-antiangiogenic effects, @entity4020 and @entity12698 , an oral @entity3840 inhibitor, were tested in metastatic @entity1358 @entity1 . METHODS: @entity1 with untreated, metastatic @entity1358 received @entity4020 3 MU s.c. daily and @entity12698 400 mg p.o. BID continuously until disease progression or unacceptable @entity137 . Plasma for @entity540 and @entity7 levels was collected at baseline, end of cycles 1, 2, and every other cycle until off-study. Parffin-embedded @entity1358 samples were stained for @entity3840 expression. A 50% increase in the median @entity74 ( @entity74 ) versus historical controls was sought as the primary endpoint. RESULTS: Twenty @entity1 have been treated to date. Two partial responses (10%) have been observed. The median @entity74 is 3.4 months (range 1.2-9.3+ months). There was no increase in observed @entity137 over what was expected from @entity4020 alone. Dose reduction for @entity137 was required to 2 MU QD (6 pts.) and to 1 MU QD (2 pts.). Median @entity74 was longer for pts. who had a treatment-induced decline in @entity540 levels compared with @entity1 with no decline in @entity540 levels (5.6 vs. 3.9 months). The mean % change at cycle 2 versus baseline for @entity540 was inversely correlated with @entity74 (r = -0.5, p = .05). CONCLUSIONS: Combination therapy of low dose, daily @entity4020 and @entity12698 is safe and feasible in metastatic @entity1358 . The final clinical efficacy of this combination is not yet determined. Change in @entity540 levels at cycle 2 versus baseline may predict clinical outcome. Staining of archived @entity1358 samples is ongoing. [Table: see text].
