A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Theracys Pharmacology, Pharmacokinetics, Studies, Metabolism - BCG Live (Intravesical)
Theracys Pharmacology, Pharmacokinetics, Studies, Metabolism - BCG Live (Intravesical)
CLINICAL PHARMACOLOGY
BCG Live (Intravesical) promotes a local acute inflammatory
and sub-acute granulomatous reaction with macrophage and lymphocyte infiltration
in the urothelium and lamina propria of the urinary bladder.1 The
exact mechanism of action is unknown, but the anti-tumor effect appears to be
T-lymphocyte-dependent.1
CLINICAL STUDIES
In a multicenter randomized clinical trial conducted by the
Southwest Oncology Group (SWOG), TheraCysÒ
was compared to doxorubicin hydrochloride (Adriamycin¨) in
patients with carcinoma in situ (CIS) of the urinary bladder, recurrent Ta/T1
papillary tumors of the urinary bladder, or both.2 Patients were
stratified by the presence or absence of CIS, and analyzed separately. All papillary
tumors were completely resected prior to study entry. The study endpoints were
disease-free survival and 2-year disease-free survival. TheraCysÒ
was administered intravesically weekly for 6 weeks, with an additional
single instillation at 3, 6, 12, 18 and 24 months following the initiation of
treatment (total of 11 instillations over 2 years). The initial treatment with
doxorubicin was given within 3 days of TUR, followed by 4 weekly treatments
and then by 11 monthly treatments (total of 16 instillations over 1 year). Cytology
and cystoscopy were obtained every 3 months for 2 years. A total of 285 patients
were randomized: 142 to treatment with doxorubicin (69 CIS and 73 non-CIS) and
143 to treatment with TheraCysÒ (70
CIS and 73 non-CIS). An intent-to-treat analysis was performed.
For patients with CIS, the complete response rate (i.e., negative
biopsies and urine cytology) within 6 months of the initiation of treatment
was 33% with doxorubicin and 71% with TheraCysÒ
(p<0.001, Fisher’s Exact Test). The probability of being disease-free
at 2 years was 23% with doxorubicin and 51% with TheraCysÒ
(p<0.001, Z Test). The median disease-free survival was 4.9 months
for doxorubicin and 30 months for TheraCysÒ
(p<0.001, Log Rank Test).
For patients with Ta/T1 papillary tumors only, the 2-year disease-free
survival was 29% with doxorubicin and 50% with TheraCysÒ
(p=0.008, Z Test). The median disease-free survival was 10.5 months
with doxorubicin and 22.5 months with TheraCysÒ
(p=0.001, Log Rank Test).
The results are summarized in Table 1.
|
Table No. 1: SWOG Study 8216 - Efficacy
|
| |
Carcinoma in situ
|
Ta/T1 Papillary Tumors
|
|
Doxorubicin N=69
|
TheraCysÒ N=70
|
Doxorubicin N=73
|
TheraCysÒ N=73
|
|
Complete Response
|
23 (33%)
|
50 (71%)
|
-
|
-
|
|
Median Disease-free Survival
|
4.9 Months
|
30 Months
|
10.5 Months
|
22.5 Months
|
|
2-Year Disease-free Survival
|
23%
|
51%
|
29%
|
50%
|
|
95% Confidence Interval
|
(15%, 35%)
|
(41%, 65%)
|
(20%, 41%)
|
(39%, 63%)
|
Based upon Kaplan-Meier estimates.
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