Theracys

Clinical Pharmacology

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CLINICAL PHARMACOLOGY

Theracys

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.¹The 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.²Patients 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%)