Studies of DOXIL for AIDS-related KS (Pre-HAART)

1
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
Note A total of 10 DOXIL studies of varying
design were completed for AIDS related KS
2
Publications of DOXIL for AIDS-related KS(HAART
Era)
Study No. Design DOXIL 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
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Results of Randomized Studies of Liposomal
Anthracyclines
Reference Treatment entered ( eval) Objective Response Rate () Objective Response Rate () Time-to-treatment failure (days) Time-to-treatment failure (days)
Gill et al, 1996 DaunoXome 117 (116) 25 pNS 115 p0.13
Gill et al, 1996 ABV 115 (111) 28 pNS 99 p0.13
Northfelt et al, 1998 DOXIL (2 Weeks) 133 (133) 46 plt0.001 124 p0.26
Northfelt et al, 1998 ABV 125 (125) 25 plt0.001 128 p0.26
Stewart, et al, 1998 DOXIL (3 Weeks) 121 (116) 59 plt0.001 160 pNR
Stewart, et al, 1998 BV 120 (102) 23 plt0.001 157 pNR
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.
4
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

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Clinical Presentation of Patients Treated with
DOXIL

• Advanced KS with
• No prior HAART
• HAART intolerant or failure
• Virologic and immunologic response to HAART
• Rapid KS progression on starting HAART (IRIS)

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Response of Kaposis Sarcoma to DOXIL
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Response of Kaposis Sarcoma to DOXIL
8
Response of Kaposis Sarcoma to DOXIL
9
Kaposi Sarcoma Incidence
AIDS-related KS approval
Study 30-38
Source SEER Cancer Statistics Review, 1975-2002