UNASSIGNED: 7272 Background: Exisulind (E) is an oral selective apoptotic antineoplastic drug that exerts its antitumor effect via the inhibition of @entity5 -related @entity6708 phosphodiesterase and activation of protein kinase G. E caused growth inhibition when used alone and with chemotherapy in multiple in vitro and in @entity5 models. The aim of this study is to define the maximum tolerated dose (Phase I) and efficacy (Phase II) of V + E in elderly @entity1 with IIIB/IV @entity1149 . METHODS: @entity1 (pts) were > 69 yrs of age. No prior chemotherapy was allowed. PS 0-1. Pts were entered on 3 dose levels of E (125 mg BID, 125 mg qAM and 250 mg qPM, and 250 mg BID) with V (25 mg/m(2)) given weekly in a 4 week cycle. Pts with clinical benefit (CR/PR/SD) after 6 cycles of V + E were allowed to continue on E alone Results: 14 pts were enrolled in the phase I portion of the study: 3 on dose level 1, 4 on dose level 2 and 7 on an expanded dose level 3. Median age of this group was 78 yrs (range 72-84). Dose limiting @entity137 included grade (Gr) 3 @entity1142 (1 pt) and @entity6408 diarrhea (1 pt), both at dose level 2, and Gr 4 @entity221 (1 pt) at dose level 3. The MTD of E was 125 mg BID. One PR was confirmed. 15 pts have been enrolled thus far in the phase II portion of the study (a total accrual of 30 pts is anticipated); median age is 77 yrs (range 71-81). @entity6408 /4 treatment-related @entity137 include @entity1398 (5 pts; 2 with Gr 4), @entity1431 (4 pts), @entity417 (1 pt), fatigue (3 pts), @entity1353 (2 pts), and @entity1142 (1 pt). 12 pts are evaluable for response: 2 PRs have been confirmed. The preliminary median survival for pts in the phase II portion of the study to date @entity4318 weeks (range 1 - 49+ weeks). CONCLUSIONS: E does not appear to worsen the @entity137 of V in untreated elderly @entity1 with advanced @entity1149 . The phase II portion of this study is on-going. [Table: see text].

Phase I/II study of exisulind (E) and vinorelbine (V) in elderly @entity1 with advanced @entity1149 ( XXXX ).

@entity6708 :: ('CHEBI:16356', 'Chemical') :: ['cGMP'] @entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'toxicities'] @entity4318 :: ('MESH:C038399', 'Chemical') :: ['is 23'] @entity417 :: ('MESH:D000740', 'Disease') :: ['anemia'] @entity1353 :: ('MESH:D004417', 'Disease') :: ['dyspnea'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'vivo tumor'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC'] @entity6408 :: ('10507', 'Gene') :: ['Gr 3'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenia'] @entity1431 :: ('MESH:D007970', 'Disease') :: ['leukopenia'] @entity1142 :: ('MESH:D003248', 'Disease') :: ['constipation'] @entity221 :: ('MESH:D005334', 'Disease') :: ['neutropenic fever']
@entity1149 :: (MESH:D002289,Disease) :: ['NSCLC']
