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Allergic Reaction to Intravesical Adriamycin
:PF:1NCIPLES OF ONCOLOGY AND HvHvHJNOLOGY, AND BLADDER rf'UMGRS
for body coil lVfllL The authors conclude that use of the double surface coil results in more accurate MRI staging of bladder cance:r compared to conventional body coi.l MRI. Th.is conclusion must :remain tentative pending larger clinical t:riafo of patients with all stages of disease with more complete su:rgical staging. Moreover, even with double surface coil MRI staging errors are considerable. William J. Catalona, M.D. Allergic Reaction to Intravesical Adriamycin
B. R. P. BIRCH AND J. C. CRISP, Department of Urology, Watford General Hospital, Watford, England Brit. J. Urol., 61: 165-166, 1988 Allergic reaction to intravesical Adriamycin has not been reported in the United Kingdomo We now describe such a case. Editorial Comment: Intravesical doxorubicin is an antibiotic cytotoxic agent that has been used with efficacy for intravesical instillation therapy in patients with superficial bladder cancer. This agent frequently produces moderate chemical cystitis but well documented allergic reactions have not been reported frequently. Previous studies have shown that little of the intravesical dose of doxorubicin is absorbed, presumably because of its :relatively large molecular weight. The authors report on a patient treated with intravesical doxoru.bicin foy recurrent superficial bladder cancer who had an apparent allergic reaction after treatment 12. The reaction was characterized by erythema, pruritl.s and chest tightness, and it subsided with corticosteroid administration, Following the allergic reaction another inb·avesical dose of doxorubicin was given, which also produced an allergic reaction. The patient had been treated previously with thiotepa and subsequently with ethoglucid (Epodyl) with no apparent adverse consequences. Also, intravesical administration of lactose in saline solution a§ a control produced no adverse side effects. WHlia.m J. Cata.Iona, M.D. Does Bacilh1s Calmette-Guerin Immunotherapy Accelerate G:rtowth and Cause Metastatic Spread of Second Primary Malignancy?
0. P.
KHANNA, SON, Mo
R.
COTTONE, R. H. MAZER, N.
H.
CHOU, M. HEEG, Do L Jo READ, R. UHLMAN,
Do NUGENT AND M. FRIEDMANN, Division of Urology, Department of Surgery, and Department of Anatomy, Hahnemann University, Philadelphia, and Wilkes-Barre General Hospital, Wilkes-Barre, Pennsylvania; Bridgeton Hospital, Bridgeton, Elmer Community Hospital, Elmer and St. Francis Medical Center, Trenton, New Jersey; Paoli Memorial Hospital, Paoli, Pennsylvania, and Helene Fuld Medical Center, Trenton, New Jersey Urology, 31: 459-468, 1988
In our study, 29 of 150 patients with bladder cancer also had other associated primary malignancies, 10 of which were manifested after intravesical treatment with bacillus CalmetteGuerin (BCG). Second primary malignancies developed in 5 of these patients within three months of the start of ECG therapy. All 5 showed acceleration of the second primary tumor, and
449
distant metastatic lesions developed in 4. In the other 5 patients nonbladder primary malignancies developed eight months or more after intravesical BCG therapy started, but did not show acceleration or spreado Twenty patients with other primary malignancies that had developed months to years before intravesical therapy did not show acceleration or spread of those tumors. Vv e have seen enough cases of patients who received intravesical BCG at the time of growth and spread of second primary malignancies to warrant concern. Animal and human studies of BCG use for treatment of malignancy indicate that the temporal relationship between the starting point of tumor development and the starting point of ECG treatment is crucial in determining whether BCG will eradicate or exacerbate the tumor. We have therefore instituted a change in our treatment until the question of whether or not BCG causes the appearance and spread of these second malignancies is answered. Editorial Comment: Intravesical bacillu§ CalmetteGeurin (BCG) therapy has been used as an effective adjunct in the treatment of patients with superficial bladder cancer. Although the exact mechanism(s) of action of BCG therapy are not known, there is accumulating evidence that immunological mechanisms are involved" Several investigators of experimental animal tumors have .reported evidence that BCG therapy may cause perturbations of the host immunological system that may result in accelerated tumor growth. There is little reported evidence that bears upon this question in humans treated with intravesical BCG therapy for superficial bladder cancer. It is well established that patients having 1 form of cancer have a significantly higher incidence of another cancer. This is true particularly with bladder cancer, which has a strong association with cigarette smoking and exposure to other carcinogens. The authors report that 29 of 150 bladder cancer patients (20 per cent) had other primary malignancies, 10 (6 per cent) of which occurred after intravesical BCG therapy. In 3 of these patients the second tumor was a transitional cell carcinoma of the renal pelvis. These latter cases probably represent field change disease rather than second malignancies. The authors (rightly) do not draw any conclusions from this observation but make a plea for consideration of the possibility that BCG may actually be harmful to some patients. To address this question properly would l"equire a case-controlled epidemiological study using modern statistical methods. William J. Catalo:na, M.D. Alpha-Interferon in Superficial Bladder Cancer: A Northern California Oncology Group Study F. M. TORTI, L. D. SHORTLIFFE, R. Do WILLIAMS, W. C. PITTS, R. L. KEMPSON, J. C. Ross, J. PALMER, F. MEYERS, M. FERRARI, J. HANNIGAN, R. SPIEGEL, K. MCWHIRTER AND
F. FREIHA, Stanford University Medical Center, Palo Alto; San Francisco Veterans Administration Medical Centers, University of California at San Francisco, San Francisco; Schering Corporation; University of California at Davis, Davis, and the Northern California Oncology Group, California
J. Clin. Oncol., 6: 476-483, 1988
Thirty-five patients with superficial transitional carcinoma of the bladder were treated intravesically with escalating doses
for body coil lVfllL The authors conclude that use of the double surface coil results in more accurate MRI staging of bladder cance:r compared to conventional body coi.l MRI. Th.is conclusion must :remain tentative pending larger clinical t:riafo of patients with all stages of disease with more complete su:rgical staging. Moreover, even with double surface coil MRI staging errors are considerable. William J. Catalona, M.D. Allergic Reaction to Intravesical Adriamycin
B. R. P. BIRCH AND J. C. CRISP, Department of Urology, Watford General Hospital, Watford, England Brit. J. Urol., 61: 165-166, 1988 Allergic reaction to intravesical Adriamycin has not been reported in the United Kingdomo We now describe such a case. Editorial Comment: Intravesical doxorubicin is an antibiotic cytotoxic agent that has been used with efficacy for intravesical instillation therapy in patients with superficial bladder cancer. This agent frequently produces moderate chemical cystitis but well documented allergic reactions have not been reported frequently. Previous studies have shown that little of the intravesical dose of doxorubicin is absorbed, presumably because of its :relatively large molecular weight. The authors report on a patient treated with intravesical doxoru.bicin foy recurrent superficial bladder cancer who had an apparent allergic reaction after treatment 12. The reaction was characterized by erythema, pruritl.s and chest tightness, and it subsided with corticosteroid administration, Following the allergic reaction another inb·avesical dose of doxorubicin was given, which also produced an allergic reaction. The patient had been treated previously with thiotepa and subsequently with ethoglucid (Epodyl) with no apparent adverse consequences. Also, intravesical administration of lactose in saline solution a§ a control produced no adverse side effects. WHlia.m J. Cata.Iona, M.D. Does Bacilh1s Calmette-Guerin Immunotherapy Accelerate G:rtowth and Cause Metastatic Spread of Second Primary Malignancy?
0. P.
KHANNA, SON, Mo
R.
COTTONE, R. H. MAZER, N.
H.
CHOU, M. HEEG, Do L Jo READ, R. UHLMAN,
Do NUGENT AND M. FRIEDMANN, Division of Urology, Department of Surgery, and Department of Anatomy, Hahnemann University, Philadelphia, and Wilkes-Barre General Hospital, Wilkes-Barre, Pennsylvania; Bridgeton Hospital, Bridgeton, Elmer Community Hospital, Elmer and St. Francis Medical Center, Trenton, New Jersey; Paoli Memorial Hospital, Paoli, Pennsylvania, and Helene Fuld Medical Center, Trenton, New Jersey Urology, 31: 459-468, 1988
In our study, 29 of 150 patients with bladder cancer also had other associated primary malignancies, 10 of which were manifested after intravesical treatment with bacillus CalmetteGuerin (BCG). Second primary malignancies developed in 5 of these patients within three months of the start of ECG therapy. All 5 showed acceleration of the second primary tumor, and
449
distant metastatic lesions developed in 4. In the other 5 patients nonbladder primary malignancies developed eight months or more after intravesical BCG therapy started, but did not show acceleration or spreado Twenty patients with other primary malignancies that had developed months to years before intravesical therapy did not show acceleration or spread of those tumors. Vv e have seen enough cases of patients who received intravesical BCG at the time of growth and spread of second primary malignancies to warrant concern. Animal and human studies of BCG use for treatment of malignancy indicate that the temporal relationship between the starting point of tumor development and the starting point of ECG treatment is crucial in determining whether BCG will eradicate or exacerbate the tumor. We have therefore instituted a change in our treatment until the question of whether or not BCG causes the appearance and spread of these second malignancies is answered. Editorial Comment: Intravesical bacillu§ CalmetteGeurin (BCG) therapy has been used as an effective adjunct in the treatment of patients with superficial bladder cancer. Although the exact mechanism(s) of action of BCG therapy are not known, there is accumulating evidence that immunological mechanisms are involved" Several investigators of experimental animal tumors have .reported evidence that BCG therapy may cause perturbations of the host immunological system that may result in accelerated tumor growth. There is little reported evidence that bears upon this question in humans treated with intravesical BCG therapy for superficial bladder cancer. It is well established that patients having 1 form of cancer have a significantly higher incidence of another cancer. This is true particularly with bladder cancer, which has a strong association with cigarette smoking and exposure to other carcinogens. The authors report that 29 of 150 bladder cancer patients (20 per cent) had other primary malignancies, 10 (6 per cent) of which occurred after intravesical BCG therapy. In 3 of these patients the second tumor was a transitional cell carcinoma of the renal pelvis. These latter cases probably represent field change disease rather than second malignancies. The authors (rightly) do not draw any conclusions from this observation but make a plea for consideration of the possibility that BCG may actually be harmful to some patients. To address this question properly would l"equire a case-controlled epidemiological study using modern statistical methods. William J. Catalo:na, M.D. Alpha-Interferon in Superficial Bladder Cancer: A Northern California Oncology Group Study F. M. TORTI, L. D. SHORTLIFFE, R. Do WILLIAMS, W. C. PITTS, R. L. KEMPSON, J. C. Ross, J. PALMER, F. MEYERS, M. FERRARI, J. HANNIGAN, R. SPIEGEL, K. MCWHIRTER AND
F. FREIHA, Stanford University Medical Center, Palo Alto; San Francisco Veterans Administration Medical Centers, University of California at San Francisco, San Francisco; Schering Corporation; University of California at Davis, Davis, and the Northern California Oncology Group, California
J. Clin. Oncol., 6: 476-483, 1988
Thirty-five patients with superficial transitional carcinoma of the bladder were treated intravesically with escalating doses