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Use of Furacin in Treatment of Testicular Tumors: A Report of Three Cases
THE JOURNAL OF UROLOGY
Vol. 85, No. 4 April 1961 Copyright © 1961 by The Williams & Wilkins Co. Printed in U.S.A.
USE OF FURACIN IN TREATMENT OF TESTICULAR TUMORS: A REPORT OF THREE CASES M. P. WESTFALL, M.A. GARCIA
AND
H. KAVOOKJIAN
From the Veterans Administration Hospital, Bronx 68, N. Y.
Furacin (5 nitro-2-furaldehyde semicarbazone) is a furan derivative which has been used in the treatment of testicular tumors. Studies by Prior and Ferguson on effects of nitrofuran on the testes of rats revealed that nitrofurans exert a more specific degenerative effect upon testicular germinal epithelium in the rat than could be produced with nitrogen mustard. Green and Friedgood noted that furacin when administered subcutaneously delayed the growth of mouse sarcoma. These observations led to the clinical use of furacin in carcinoma of the testicle. The first clinical report was by Wildermuth in 1955. Furacin was used to treat a case of embryonal cell carcinoma of the testis with pulmonary metastases, with complete regression. The patient remained without clinical evidence of disease lH years. At autopsy 2 years later lungs showed scars throughout with no evidence of tumor at sites estimated to be areas of previous metastases. The brain showed extensive metastases of choriocarcinoma. Friedgood, Danza and Boccabella treated 4 cases of seminoma and noted marked degeneration of tumor cells, increased fibrosis, and decreased cellularity of the tumor. Politano, G. W. Leadbetter and W. F. Leadbetter reported 1 case of seminoma with pulmonary metastases where furacin failed to alter the course of the tumor. Severe peripheral neuritis failed to respond to treatment with crude liver extract, and vitamin B complex. CASE REPORTS
Case 1. '{{. B., a 32-year-old white man, was admitted on April 9, 1958 with swelling of the left testis of 5 months' duration. Three months earlier he had been a patient at another hospital where a testicular biopsy had been performed on February 15. JVIicroscopic study revealed adenocarcinoma. No further treatment was mAccepted for publication August 16, 1960.
stituted until the present admission. During the ensuing 2 months there was gradual enlargement of the testicle plus development of gynecomastia. Physical examination revealed that the left testis was three times normal size, stony hard, heavy and tender. The right testis was normal. There was bilateral tender enlargement of the breast. Laboratory studies: Hemoglobin 13 gm., white blood cells 4500, urine acid, specific gravity 1.022. A-Z test was positive. The admission chest x-ray was negative. An intravenous urogram showed some lateral displacement of the midportion of the left ureter. A left orchiectomy was performed on April 11. Microscopic examination of the tissue revealed malignant teratocarcinoma with invasion of the vessels of the spermatic cord. Radiotherapy was administered for a period of approximately fifty days, total dose being 400r. Chest x-rays on May 26 revealed the presence of a mass in the region of the hilus of the left lung. This slowly increased in size and on October 7, other nodular masses were noted in the right lung field. A metastasis also appeared in the left supraclavicular lymph nodes. Furacin therapy was commenced August 13. The patient received 0.5 gm. every 8 hours for a total of 52 gm. Soon after the conclusion of this treatment the patient began to complain of numbness, pain and tingling in the hands and feet. Peripheral neuritis was diagnosed; this was of such severe degree that motor paralysis and atrophy of the intrinsic muscles of the hands and feet developed. The neuritis failed to improve in spite of massive doses of vitamin B complex. In November 1958, radiotherapy was once again administered to multiple sites including 4000r to the left supraclavicular node, 3000r to the mediastinum and 155r to the right lower lung. In January 1959, a mass and erythema appeared; a spontaneous sigmoid colostomy also 606
EFFECT OF FURACIN ON TESTICULAR TUMOR
developed. This was presumably due to tumor. The patient continued to lose weight. He required large doses of analgesics for relief of neuritic pain. He died on July 26 from respiratory embarassment, due to metastatic tumor. Autopsy revealed teratocarcinoma of left testicle with massive metastases to both lungs, mediastinum, diaphragm, retroperitoneal and pelvic nodes and liver. Case 2. G. J., a 32-year-old white man, had an enlarged left testicle which had been present since January 1958. In July he was admitted to another hospital where a left orchiectomy was performed. JVIicroscopic examination of tissue revealed embryonal carcinoma of the left testicle. A chest x-ray showed bilateral pulmonary metastasis. The patient was transferred to Bronx VA Hospital for further care. Physical examination revealed a well healed left inguinal scar. The left testis was surgically absent . The right testicle was normal. Laboratory studies: Hemoglobin 13 gm., urinalysis normal. A-Z test negative. A chest film on admission revealed multiple metastases throughout both lung fields. On admission patient received 2000 r over the left lung field. Some decrease was noticed in size of the metastatic nodules on the left side. However, the metastasis to the right lung field gradually increased. Oral furacin 0.5 gm. every 8 hours was started on August 18. The patient received the total dose of 55 gm. furacin. The weight loss continued, some nausea and anorexia developed and numbness, pain and tingling were noticed in the hands and feet. Serial chest x-rays failed to show any decrease in size or number of pulmonary metastasis. The patient had a progresively downhill course and died October 26. No autopsy was obtained. Case 3. E. E., a 29-year-old white man, noticed swelling in left testicle 4 months prior to admission. Two months later he was admitted to another hospital where a left orchiectomy was perfonned. Retroperitoneal exploration revealed massive preaortic metastasis. A left nephrectomy ,vas performed because the ureter was obstructed by tumor. He was then referred to our hospital for radiotherapy. Physical examination revealed a well healed midline abdominal incision and a left inguinal scar. The left testis was surgically absent. The
507
right testis was normal. Palpable lymph nodes were found in the left supraclavicular region. Laboratory studies: Chest x-rays showed bi.lateral pulmonary metastatic nodule8 and mediastinal metastases. Serial x-rays showed progressive enlargement of the metastatic nodules in both lung fields. A skeletal survey failed to show metastases to bone. Urine was negative for proIan A. Radiotherapy was administered, 2000r, to the left chest and mediastinum; 1600r to each supraclavicular area. Oral furacin was administered August 8-23. When 3 gm. furacin had been taken the patient had severe nausea and vomiting which could not be controlled with antiemetics. Repeated trials with the drug had to be discontinued because of gastrointestinal side effects which prevented the administration of a therapeutic close. The patient was discharged on October 2. He died of his disease at another hospital on March 27, 1959. Postmortem examination revealed wide., spread metastatic disease to lungs and liveL DISCUSSION
Furacin has been mentioned 111 several in stances as causing regression of metastases in embryonal carcinoma of the testis CYVilclermuth) and sern.inoma (Friedgood, Danza and Boccabella). In our experience, furacin did not appreciably influence the course of malignancy in the patients. All the patients died within two years following the onset of disease. Furacin caused considerable side effects, the most noticeable of which was peripheral neuritis. This occurred in two of our patients; severe in one instance and milder in another. In the last case, persistent nausea and vomiting prevented completion of the course of chemotherapy. These experiences were similar to those reported by Politano and Leadbetter in their treatment of case of seminoma with puhnonary metastases. In all of our cases no radiographic evidence of even temporary regression of pulmonary metastatic nodules could be attributed to the furacin, SUMMARY
Three cases of testicular tumor, one case of teratocarcinoma and two cases of embryonal carcinoma, are presented. Two of these cases were treated with orchiectomy, radiation, and furacin.
608
WESTFALL, GARCIA AND KAVOOKJIAN
One patient with embryonal carcinoma could not tolerate the complete course of chemotherapy. Oral furacin was accompanied by peripheral neuritis and occasionally nausea and vomiting. All our patients died within two years of the onset of disease.
REFERENCES FRIEDGOOD, C. E., DANZA, A. L. AND BoccABELLA, A.: Cancer Res., 12: 262-263, 1952. GREEN, M. N. AND FRIEDGOOD, C. E.: Proc. Soc. Exp. Biol. and Med., 69: 603-604, 1948. POLITANO, V. A., LEADBETTER, G. w. AND LEADBETTER, W. F.: J. Urol., 79: 771, 1958. WILDERMUTH, 0.: Radiology, 65: 599, 1955.
Vol. 85, No. 4 April 1961 Copyright © 1961 by The Williams & Wilkins Co. Printed in U.S.A.
USE OF FURACIN IN TREATMENT OF TESTICULAR TUMORS: A REPORT OF THREE CASES M. P. WESTFALL, M.A. GARCIA
AND
H. KAVOOKJIAN
From the Veterans Administration Hospital, Bronx 68, N. Y.
Furacin (5 nitro-2-furaldehyde semicarbazone) is a furan derivative which has been used in the treatment of testicular tumors. Studies by Prior and Ferguson on effects of nitrofuran on the testes of rats revealed that nitrofurans exert a more specific degenerative effect upon testicular germinal epithelium in the rat than could be produced with nitrogen mustard. Green and Friedgood noted that furacin when administered subcutaneously delayed the growth of mouse sarcoma. These observations led to the clinical use of furacin in carcinoma of the testicle. The first clinical report was by Wildermuth in 1955. Furacin was used to treat a case of embryonal cell carcinoma of the testis with pulmonary metastases, with complete regression. The patient remained without clinical evidence of disease lH years. At autopsy 2 years later lungs showed scars throughout with no evidence of tumor at sites estimated to be areas of previous metastases. The brain showed extensive metastases of choriocarcinoma. Friedgood, Danza and Boccabella treated 4 cases of seminoma and noted marked degeneration of tumor cells, increased fibrosis, and decreased cellularity of the tumor. Politano, G. W. Leadbetter and W. F. Leadbetter reported 1 case of seminoma with pulmonary metastases where furacin failed to alter the course of the tumor. Severe peripheral neuritis failed to respond to treatment with crude liver extract, and vitamin B complex. CASE REPORTS
Case 1. '{{. B., a 32-year-old white man, was admitted on April 9, 1958 with swelling of the left testis of 5 months' duration. Three months earlier he had been a patient at another hospital where a testicular biopsy had been performed on February 15. JVIicroscopic study revealed adenocarcinoma. No further treatment was mAccepted for publication August 16, 1960.
stituted until the present admission. During the ensuing 2 months there was gradual enlargement of the testicle plus development of gynecomastia. Physical examination revealed that the left testis was three times normal size, stony hard, heavy and tender. The right testis was normal. There was bilateral tender enlargement of the breast. Laboratory studies: Hemoglobin 13 gm., white blood cells 4500, urine acid, specific gravity 1.022. A-Z test was positive. The admission chest x-ray was negative. An intravenous urogram showed some lateral displacement of the midportion of the left ureter. A left orchiectomy was performed on April 11. Microscopic examination of the tissue revealed malignant teratocarcinoma with invasion of the vessels of the spermatic cord. Radiotherapy was administered for a period of approximately fifty days, total dose being 400r. Chest x-rays on May 26 revealed the presence of a mass in the region of the hilus of the left lung. This slowly increased in size and on October 7, other nodular masses were noted in the right lung field. A metastasis also appeared in the left supraclavicular lymph nodes. Furacin therapy was commenced August 13. The patient received 0.5 gm. every 8 hours for a total of 52 gm. Soon after the conclusion of this treatment the patient began to complain of numbness, pain and tingling in the hands and feet. Peripheral neuritis was diagnosed; this was of such severe degree that motor paralysis and atrophy of the intrinsic muscles of the hands and feet developed. The neuritis failed to improve in spite of massive doses of vitamin B complex. In November 1958, radiotherapy was once again administered to multiple sites including 4000r to the left supraclavicular node, 3000r to the mediastinum and 155r to the right lower lung. In January 1959, a mass and erythema appeared; a spontaneous sigmoid colostomy also 606
EFFECT OF FURACIN ON TESTICULAR TUMOR
developed. This was presumably due to tumor. The patient continued to lose weight. He required large doses of analgesics for relief of neuritic pain. He died on July 26 from respiratory embarassment, due to metastatic tumor. Autopsy revealed teratocarcinoma of left testicle with massive metastases to both lungs, mediastinum, diaphragm, retroperitoneal and pelvic nodes and liver. Case 2. G. J., a 32-year-old white man, had an enlarged left testicle which had been present since January 1958. In July he was admitted to another hospital where a left orchiectomy was performed. JVIicroscopic examination of tissue revealed embryonal carcinoma of the left testicle. A chest x-ray showed bilateral pulmonary metastasis. The patient was transferred to Bronx VA Hospital for further care. Physical examination revealed a well healed left inguinal scar. The left testis was surgically absent . The right testicle was normal. Laboratory studies: Hemoglobin 13 gm., urinalysis normal. A-Z test negative. A chest film on admission revealed multiple metastases throughout both lung fields. On admission patient received 2000 r over the left lung field. Some decrease was noticed in size of the metastatic nodules on the left side. However, the metastasis to the right lung field gradually increased. Oral furacin 0.5 gm. every 8 hours was started on August 18. The patient received the total dose of 55 gm. furacin. The weight loss continued, some nausea and anorexia developed and numbness, pain and tingling were noticed in the hands and feet. Serial chest x-rays failed to show any decrease in size or number of pulmonary metastasis. The patient had a progresively downhill course and died October 26. No autopsy was obtained. Case 3. E. E., a 29-year-old white man, noticed swelling in left testicle 4 months prior to admission. Two months later he was admitted to another hospital where a left orchiectomy was perfonned. Retroperitoneal exploration revealed massive preaortic metastasis. A left nephrectomy ,vas performed because the ureter was obstructed by tumor. He was then referred to our hospital for radiotherapy. Physical examination revealed a well healed midline abdominal incision and a left inguinal scar. The left testis was surgically absent. The
507
right testis was normal. Palpable lymph nodes were found in the left supraclavicular region. Laboratory studies: Chest x-rays showed bi.lateral pulmonary metastatic nodule8 and mediastinal metastases. Serial x-rays showed progressive enlargement of the metastatic nodules in both lung fields. A skeletal survey failed to show metastases to bone. Urine was negative for proIan A. Radiotherapy was administered, 2000r, to the left chest and mediastinum; 1600r to each supraclavicular area. Oral furacin was administered August 8-23. When 3 gm. furacin had been taken the patient had severe nausea and vomiting which could not be controlled with antiemetics. Repeated trials with the drug had to be discontinued because of gastrointestinal side effects which prevented the administration of a therapeutic close. The patient was discharged on October 2. He died of his disease at another hospital on March 27, 1959. Postmortem examination revealed wide., spread metastatic disease to lungs and liveL DISCUSSION
Furacin has been mentioned 111 several in stances as causing regression of metastases in embryonal carcinoma of the testis CYVilclermuth) and sern.inoma (Friedgood, Danza and Boccabella). In our experience, furacin did not appreciably influence the course of malignancy in the patients. All the patients died within two years following the onset of disease. Furacin caused considerable side effects, the most noticeable of which was peripheral neuritis. This occurred in two of our patients; severe in one instance and milder in another. In the last case, persistent nausea and vomiting prevented completion of the course of chemotherapy. These experiences were similar to those reported by Politano and Leadbetter in their treatment of case of seminoma with puhnonary metastases. In all of our cases no radiographic evidence of even temporary regression of pulmonary metastatic nodules could be attributed to the furacin, SUMMARY
Three cases of testicular tumor, one case of teratocarcinoma and two cases of embryonal carcinoma, are presented. Two of these cases were treated with orchiectomy, radiation, and furacin.
608
WESTFALL, GARCIA AND KAVOOKJIAN
One patient with embryonal carcinoma could not tolerate the complete course of chemotherapy. Oral furacin was accompanied by peripheral neuritis and occasionally nausea and vomiting. All our patients died within two years of the onset of disease.
REFERENCES FRIEDGOOD, C. E., DANZA, A. L. AND BoccABELLA, A.: Cancer Res., 12: 262-263, 1952. GREEN, M. N. AND FRIEDGOOD, C. E.: Proc. Soc. Exp. Biol. and Med., 69: 603-604, 1948. POLITANO, V. A., LEADBETTER, G. w. AND LEADBETTER, W. F.: J. Urol., 79: 771, 1958. WILDERMUTH, 0.: Radiology, 65: 599, 1955.