1 8 November 2005 ODAC: DOXIL ® , AIDS-related KS Studies of DOXIL for AIDS-related KS (Pre-HAART) Study No. Design No. of pts. Objective Response Rate/Results 30-10 Phase 3 comparison to ABV 258 DOXIL (46.2%) vs. ABV (25.6%) 30-11 Phase 3 comparison to BV 241 DOXIL (58.7%) vs. BV (23.3%) 30-12 Open-label, non-comparative extension 871 DOXIL (65.9%) (n = 41 patients w/prior therapy) 30-14 Randomized, crossover, PK and tumor localization 43 DOXIL selectively accumulates into KS lesions No significant differences in PK parameters b/w doses 30-21 Phase 1/2, cardiac biopsy data; comparison to cardiac damage 10 Less myocardial damage observed in patients treated with DOXIL compared to their matched doxorubicin controls : A total of 10 DOXIL studies of varying design were completed for AIDS related KS
Studies of DOXIL for AIDS-related KS (Pre-HAART). Note: A total of 10 DOXIL studies of varying design were completed for AIDS related KS. Publications of DOXIL for AIDS-related KS (HAART Era). Results of Randomized Studies of Liposomal Anthracyclines. - PowerPoint PPT Presentation
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18 November 2005 ODAC: DOXIL®, AIDS-related KS
Studies of DOXIL for AIDS-related KS(Pre-HAART)
Study No. Design
No. of pts. Objective Response Rate/Results
30-10 Phase 3 comparison to ABV
258 DOXIL (46.2%) vs. ABV (25.6%)
30-11 Phase 3 comparison to BV 241 DOXIL (58.7%) vs. BV (23.3%)
30-14 Randomized, crossover, PK and tumor localization
43 DOXIL selectively accumulates into KS lesions
No significant differences in PK parameters b/w doses
30-21 Phase 1/2, cardiac biopsy data; comparison to cardiac damage
10 Less myocardial damage observed in patients treated with DOXIL compared to their matched doxorubicin controls
Note: A total of 10 DOXIL studies of varying design were completed for AIDS related KS
28 November 2005 ODAC: DOXIL®, AIDS-related KS
Publications of DOXIL for AIDS-related KS(HAART Era)
Study No. DesignDOXIL Treatment
(mg/m2)No. of pts. Results
Nunez Prospective, non-comparative, multicenter
DOXIL + HAART 79 79% response rate
Median time to response ~ 42 days
Martin-Carbonero
Randomized, open-label, multicenter
DOXIL 20mg/m2 every 3-weeks
28 20% HAART (N = 15)
76% HAART + DOXIL (N = 13)
Lichterfeld Uncontrolled, multicenter, observational study with matched controls
DOXIL + HAART 108 81.5% response rate
Recovery of CD4 counts not impaired by combination therapy
Hernandez Prospective, single arm, open-label, single center
DOXIL 20 mg/m2 every 3-weeks for 6 cycles
15 100% - GI response rate
53% Cutaneous response rate
38 November 2005 ODAC: DOXIL®, AIDS-related KS
Results of Randomized Studies of Liposomal Anthracyclines
NOTE: # = number; eval. = evaluable; A = Adriamycin (doxorubicin); B = bleomycin; V = vincristine; NS = not significant; NR = not reported. * includes complete and partial responses † this study reported mean survival times of 239 days for DOXIL, versus 160 days for bleomycin and vincristine.
Reference Treatment# entered
(# eval)Objective Response
Rate (%)*Time-to-treatment
failure (days)
Gill et al, 1996
DaunoXome 117 (116) 25%p=NS
115p=0.13
ABV 115 (111) 28% 99
Northfelt et al, 1998
DOXIL (2 Weeks) 133 (133) 46%
p<0.001124
p=0.26ABV 125 (125) 25% 128
Stewart, et al, 1998 †
DOXIL (3 Weeks) 121 (116) 59% p<0.001 160
p=NRBV 120 (102) 23% 157
48 November 2005 ODAC: DOXIL®, AIDS-related KS
Documentation for ACTG Criteria Biopsy Cutaneous lesions
– Number– Character (flat or raised)
Tumor-associated edema 3-5 marker lesions
– Bi-dimensional measurement Visceral lesions
– Radiographic evaluation – Bronchoscopy and endoscopy
58 November 2005 ODAC: DOXIL®, AIDS-related KS
Clinical Presentation of Patients Treated with DOXIL
Advanced KS with:– No prior HAART– HAART intolerant or failure– Virologic and immunologic response to HAART