A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder: trial

A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder

N = 262

Population

Patients with rapidly recurrent stage Ta or T1 transitional-cell carcinoma of the bladder, or carcinoma in situ (262 eligible patients).

Design

Multi-institutional randomised comparison of intravesical doxorubicin with BCG given both intravesically and percutaneously, in patients with rapidly recurrent stage Ta or T1 or in situ transitional-cell carcinoma of the bladder. 262 eligible patients, median follow-up 65 months. Complete responses in carcinoma in situ were confirmed by biopsy and urine cytology. The trial name and protocol number are not stated in the abstract.

Arms

Intravesical doxorubicin (control): Doxorubicin administered intravesically
BCG (experimental): BCG administered both intravesically and percutaneously

People

Lamm DL

Δ 60-month DFS+20 pointsΔ median Time to treatment failure+12.1 monthsΔ Complete response in carcinoma in situ+36 pointsΔ median Time to treatment failure+33.9 monthsΔ 60-month DFS+27 points

Show the numbers

Results reported for A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder
Endpoint	Analysis	BCG	Intravesical doxorubicin	Effect
DFSPatients with Ta and T1 tumours without carcinoma in situEstimated probability of being disease free at five years	primarymedian follow-up 65 monthsLamm 1991	37% at 5 y	17% at 5 y	P=0.015No confidence interval is given in the abstract.
Time to treatment failurePatients with Ta and T1 tumours without carcinoma in situTermination of treatment because of persistence, recurrence or progression of disease	primarymedian follow-up 65 monthsLamm 1991	median 22.5 months	median 10.4 months	No test or interval is given for this comparison in the abstract.
Complete response in carcinoma in situPatients with carcinoma in situEstimated probability of documented disappearance of disease, confirmed by biopsy and urine cytology	primarymedian follow-up 65 monthsLamm 1991	70%	34%	P<0.00123 of 67 patients with doxorubicin and 45 of 64 with BCG.
Time to treatment failurePatients with carcinoma in situTermination of treatment because of persistence, recurrence or progression of disease	primarymedian follow-up 65 monthsLamm 1991	median 39 months	median 5.1 months	—
DFSPatients with carcinoma in situEstimated probability of being disease free at five years	primarymedian follow-up 65 monthsLamm 1991	45% at 5 y	18% at 5 y	The abstract words this as 'disease-free at five years survival'; no interval or test is given.

Results reported for A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder
Endpoint	Analysis	BCG	Intravesical doxorubicin	Effect
DFSPatients with Ta and T1 tumours without carcinoma in situEstimated probability of being disease free at five years	primarymedian follow-up 65 monthsLamm 1991	37% at 5 y	17% at 5 y	P=0.015No confidence interval is given in the abstract.
Time to treatment failurePatients with Ta and T1 tumours without carcinoma in situTermination of treatment because of persistence, recurrence or progression of disease	primarymedian follow-up 65 monthsLamm 1991	median 22.5 months	median 10.4 months	No test or interval is given for this comparison in the abstract.
Complete response in carcinoma in situPatients with carcinoma in situEstimated probability of documented disappearance of disease, confirmed by biopsy and urine cytology	primarymedian follow-up 65 monthsLamm 1991	70%	34%	P<0.00123 of 67 patients with doxorubicin and 45 of 64 with BCG.
Time to treatment failurePatients with carcinoma in situTermination of treatment because of persistence, recurrence or progression of disease	primarymedian follow-up 65 monthsLamm 1991	median 39 months	median 5.1 months	—
DFSPatients with carcinoma in situEstimated probability of being disease free at five years	primarymedian follow-up 65 monthsLamm 1991	45% at 5 y	18% at 5 y	The abstract words this as 'disease-free at five years survival'; no interval or test is given.

Illustrative — modelled from reported values, not trial data. Time to treatment failure, primary.

Show curves

Intravesical doxorubicin (control)
BCG (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Intravesical doxorubicin	BCG
0	100.0%	100.0%
14	39.3%	65.0%
28	15.5%	42.2%
42	6.1%	27.4%
56	2.4%	17.8%

Illustrative — modelled from reported values, not trial data. Time to treatment failure, primary.

Show curves

Intravesical doxorubicin (control)
BCG (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Intravesical doxorubicin	BCG
0	100.0%	100.0%
24	3.8%	65.3%
49	0.1%	41.9%
73	0.0%	27.3%
98	0.0%	17.5%

Appears in

1991 BCG versus intravesical doxorubicin, then BCG maintenance

Sources

Lamm DL, Blumenstein BA, Crawford ED, Montie JE, Scardino P, Grossman HB, et al. A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder. N Engl J Med. 1991;325(17):1205-9.
PubMed DOI