Elwin E. Fraley

Vinblastine, bleomycin and cis-diamminedichloroplatinum in the treatment of advanced testicular carcinoma: Possible importance of longer induction and shorter maintenance schedules

Twenty-eight patients with stage III or recurrent stage I or II testicular cancer were treated with four to six cycles of vinblastine, bleomycin and cis-diamminedichloroplatinum, and then with vinblastine maintenance for one year. With a median follow-up of more than 20.5 months for all patients, complete remission has been achieved with chemotherapy and operation in 23 (82 per cent). One of these 23 patients has had a relapse, and only three are still receiving maintenance therapy. The toxicity incurred by the extra cycles of chemotherapy in patients with extensive disease was no greater than that experienced by patients receiving smaller doses of drugs. These results confirm the high response rate reported for this combination of drugs and strongly suggest that some relapses after complete remission can be prevented by longer remission induction schedules. The value of maintenance therapy is questionable and needs further study.

Serum Alpha-Fetoprotein and Human Chorionic Gonadotropin in Patients with Seminoma

We analyzed the case histories of 31 patients who initially had a diagnosis of seminoma and elevated serum levels of alpha-fetoprotein or human chorionic gonadotropin. We concluded that an elevated alpha-fetoprotein level is firm evidence of the presence of non-seminomatous germ cell tumor and that the patient should be treated accordingly. However, if the level of human chorionic gonadotropin alone is elevated the diagnosis may be either non-seminomatous tumor or seminoma. Patients with seminoma and an elevated level of human chorionic gonadotropin do respond well to radiation therapy if they have low stage disease but if metastatic seminoma is present an elevated human chorionic gonadotropin level appears to be a poor prognostic sign if conventional treatment is given. A plan of treatment is proposed for these patients.

Stage II nonseminomatous testicular cancer: a 10-year experience.

Between 1970 and 1980, 82 patients with pathologic stage II nonseminomatous germ cell testicular carcinoma were treated at the University of Minnesota. Of the 30 patients treated with a retroperitoneal lymph node dissection, 22 (77%) relapsed. Of the 18 patients treated with retroperitoneal lymph node dissection and adjuvant radiotherapy, 12 (63%) relapsed. Sixteen patients received adjuvant chemotherapy before 1976, and 14 (87.5%) relapsed. After 1976, 18 patients received adjuvant chemotherapy (11 with cisplatin) and 2 (11%) have relapsed. No patient treated with cisplatin-based adjuvant chemotherapy has relapsed. The toxicity has been modest. Cisplatin-based chemotherapy is an effective and a safe adjuvant therapy for stage II nonseminomatous germ cell testicular carcinoma.

Viral Neoplastic Transformation of Hamster Prostate Tissue in vitro

Cultures of hamster prostatic tissues infected with simian virus 40 undergo transformation in vitro, and the transformed cells produce malignant tumors when injected into homologous hosts. Tartrate-inhibited acid phosphastase is found in the cultures of transformed cells and in the tumors they produce. Tartrate-inhibited acid phosphatase activity is elevated in the serum of tumor-bearing animals.

Pursuit of the renal mass: Is ultrasound enough?

The accuracy of ultrasonography in evaluating renal masses was assessed retrospectively in 260 renal lesions detected by intravenous urography in 242 patients. The ultrasonographic diagnosis was confirmed by cyst puncture, surgery, or autopsy. Of the lesions, 168 were benign cysts, and all were diagnosed correctly by ultrasonography. The remaining 92 lesions were renal carcinomas, and 90 were diagnosed correctly by ultrasonography. In retrospect, it was clear that the two missed cancers did not fulfill all the ultrasonographic criteria for a cyst. An algorithm is presented for the differential diagnosis of renal masses primarily by ultrasonography, and the arguments in favor of operative diagnosis of renal masses are rebutted. With the approach described, invasive studies such as cyst puncture and arteriography will be required for a definitive diagnosis in fewer than 10 percent of patients, and the morbidity and expense of the diagnostic approach will be minimized, with no decrease in accuracy.

Staging of Early Nonseminomatous Germ-Cell Testicular Cancer

The common clinical staging techniques for nonseminomatous testicular cancer fail to predict the pathologic stage in a significant number of patients with Stages I, IIS, and IIA disease. Newer techniques such as ultrasonography and computed tomography are useful in more advanced disease (Stages IIB or higher), but neither can detect microscopic metastases (Stage IIA). The accuracy of clinical staging may be improved by the discovery of new tumor markers and the devising of assays for tumor‐associated antigens, but at present retroperitoneal lymphadenectomy is needed for staging as well as for treatment.

Optimal number of chemotherapy courses in advanced nonseminomatous testicular carcinoma.

BackgroundNonseminomatous germ cell tumors (NSGCT) (testicular carcinoma) are a curable disease. Stages I and II are nearly 100% curable. Stage III has had remarkable progress in attaining complete regression, but a substantial number fail to be cured. Using platinum-based regimens such as vinblastine, bleomycin, and cisplatin (VBP), or using etoposide instead of vinblastine (BEP), or without bleomycin (EP), four courses of chemotherapy have become a national standard. Based on our prior experience with mithramycin (plicamycin), which used six courses, six courses of VBP chemotherapy were utilized as our treatment goal. This report challenges the concept that “standard therapy” for stage III testicular carcinoma is four courses. MethodFrom 1976 to 1990, 74 patients with advanced NSGCT were treated with standard doses of platinum-based chemotherapies. Five or more courses were delivered to 41 patients and fewer than five courses to 33 patients. The intent of therapy was to attain as close to six courses as possible. Because of physician preference, patient adherence, or toxicity, some patients did not reach that goal. ResultsOf 33 patients receiving less than five courses, there were 28 (85%) complete responders, and 26 (78.8%) are alive. Of 41 patients receiving five or more courses, 38 (92.7%) had complete responses, and 34 (83%) are alive. One person in each group is living with nonresectable teratoma present. In the group receiving 5+ courses, two died from causes unrelated to testis cancer and had no testis cancer present. As a result of the initial treatment, there was no evidence of cancer in 24 (72.8%.) in the group receiving less than five courses and 35 (85.4%) had no cancer after five or more courses. In considering only patients with advanced level of stage III disease in contrast to minimal or moderate stage III disease, there were fewer complete regressions with less than five courses (64.3%) than with five or more courses (88.0%). ConclusionsFor minimal stage III disease, four courses of chemotherapy may be adequate. For advanced stage III disease, more chemotherapy provides fewer treatment failures. Once a complete response is achieved without restriction to an arbitrary number of courses, two additional courses may constitute a more curative regimen.

Extragonadal abdominal germ cell cancers

The charts of eleven patients with abdominal germ cell tumors were reviewed; one had a seminoma. They all had normal testes by physical examination. Therapy consisted of cisplatinbased chemotherapy and, in some cases, surgical debulking. A complete clinical response occurred in seven patients (63%). Two patients relapsed after achieving pathology complete responses and died of progressive disease despite second-line chemotherapy. All patients that failed to achieve a complete clinical response died of progressive disease. Five patients (45%) are long-term disease-free survivors, having no recurrence 4–10 years from the time of the diagnosis (median 6 years). The outcome for this group of patients did not differ significantly from that for patients with mediastinal germ cell tumors in this institution. They do not fare as well as patients with testicular cancer.

Adequacy of chemotherapy prior to cytoreductive surgery in testicular carcinoma

Removal of residual masses after cisplatin-based chemotherapy (cytoreductive surgery) for inoperable or metastatic testicular carcinoma has demonstrated that many partial regressions are defects without malignant cells. Such negative results allow a clarification of complete regression. Failure to achieve complete regression requires intensive salvage chemotherapy or bone marrow transplant. Extended initial chemotherapy could reduce these failures. Cytoreductive surgery was performed on 44 patients with inoperable stage II or stage III testicular cancer with residual defects following chemotherapy. The patients were evaluated according to whether (a) adequate treatment was given based on attaining normal markers followed by two additional courses of therapy, (b) normal markers were achieved but two additional courses were not administered, or (c) normal markers were never attained. These were subdivided into those receiving five or more courses of chemotherapy or fewer than five courses. Patients receiving two additional courses of chemotherapy after markers became normal had a low death rate (15.4%) and highest median follow-up. Fewer patients died if they had five or more courses of chemotherapy (11.8%). Of all those who attained normal markers with at least five or more courses of therapy, 10% are dead. The presence of residual malignant cells in those receiving five or more courses of therapy was 18.2% in contrast to 50% in those receiving fewer courses. Adequate chemotherapy and attainment of normal markers followed by two more courses of therapy results in fewer patients with residual malignant cells, a greater potential of cure, and less need for intensive salvage regimens.