Leiomyosarcoma of scrotum--case report and review of literature.

Leiomyosarcoma of the scrotum is a rare tumor. Cutaneous and subcutaneous leiomyosarcomas constitute the two subtypes. We report a case of cutaneous leiomyosarcoma of the scrotum in a 73-year-old man. Cutaneous leiomyosarcoma arises from the smooth muscle of the dartos or arrectores pilorum. It is often mistaken for a benign lesion. We describe the clinical and pathologic features and review the published reports of this uncommon malignancy. It is best treated by wide local excision. Inguinal lymph node dissection is not advocated, unless a high degree of suspicion is present for lymph node metastasis. Long-term follow-up is essential, because of the risk of delayed local recurrence and distant metastasis.

Bromodeoxyuridine improves the cytotoxic effect of cisplatin: a comparison with 5-fluorouracil.

We compared the effects of the radiosensitizers, 5-bromo-2'-deoxyuridine (BUdR) and 5-fluorouracil (5-FU) alone and in combination and cis-diamminedichloroplatinum (cisplatin, DDP) on the growth of B16 amelanotic melanoma (B16a) tumors in mice. In a preliminary study, tumor growth was significantly inhibited in the presence of BUdR and was further reduced with the combination of BudR and DDP. In a second experiment, BUdR was found to be more effective than 5-FU when used in combination with DDP. At the completion of the study, tumor volumes as a percentage of control values in mice treated with a single drug were as follows: 5-FU (50 mg/kg per day for 7 days) 76.5% (P < 0.05), BUdR (100 mg/kg per day for 7 days) 68% (P < 0.05) and DDP (5 mg/kg x 3) 54% (P < 0.01). Combining 5-FU and DDP at these dosages reduced volumes to 38% (P < 0.01), while BUdR + DDP-treated mice had tumor volumes only 28% (P < 0.001) the size of untreated controls. Furthermore, the toxicity, as demonstrated by a decrease in body weight and an increase in mortality, was more severe in mice receiving 5-FU than in those receiving in BUdR. DDP interacts synergistically with either BUdR or 5-FU in its cytotoxic action in vivo. No such relationship could be demonstrated in vitro, suggesting that the pharmacologic activity of these drugs may be responsible for the antitumor activity than direct cytotoxic effects. We propose that BUdR is more effective than 5-FU as a potentiator of DDP in this murine melanoma model.

Effects of cyclophosphamide alone and scheduled methotrexate-5-fluorouracil combination chemotherapy on transplantable R-3327 prostatic adenocarcinoma in F1 hybrid male rat.

Male F1 hybrid rats bearing the R-3327 transplantable adenocarcinoma demonstrating similar growth patterns within the original sample of animals were carefully separated into control and treatment groups for each growth pattern. This assured treatment of tumors with similar cell kinetics within each group. In one group, cyclophosphamide (100 mg/kg) was injected intraperitoneally once every four weeks for eight weeks (total of two doses). In the second group, methotrexate (7.5 mg/kg) followed in ninety minutes by 5-fluorouracil (50 mg/kg) were injected intraperitoneally once each week for eight weeks (total of eight doses). These drug dosages did not depress the white cell count of the animals, and they tolerated the medicines well. Excellent suppression of tumor growth was obtained in each group with the cyclophosphamide treatment group being significant at the 0.01 level and the methotrexate-5-fluorouracil treatment group being significant at the 0.05 level.

The effects of cyclophosphamide, ketoconazole, aclacinomycin-A, methotrexate, and scheduled methotrexate-5-fluorouracil combination chemotherapy on the transplantable R-3327 prostatic adenocarcinoma in the F1 hybrid male rat.

Male F1 hybrid rats bearing the R-3327 transplantable prostatic adenocarcinoma demonstrating similar growth patterns within the original sample of animals were carefully separated into control and treatment groups. This assured treatment of tumors with similar cell kinetics within each group. In the first study, two separate drug protocols were investigated by intraperitoneal injection, namely cyclophosphamide (100 mg/kg) once every 4 weeks for 8 weeks and scheduled methotrexate (7.5 mg/kg) followed in 90 minutes by 5-fluorouracil (50 mg/kg) once each week for 8 weeks. Excellent suppression of tumor growth was obtained with each treatment protocol. Both were significant at the 0.01 level. In the second study, methotrexate (100 mg/kg) intraperitoneally once each week for 6 weeks, aclacinomycin-A intraperitoneally once each week for 4 weeks, and ketoconazole (60 mg/kg) via gavage 5 times a week for 6 weeks were administered to the animals in each respective group. Aclacinomycin-A and ketoconazole showed significant suppression of tumor growth at the 0.01 and 0.05 levels, respectively. Methotrexate suppressed tumor growth, but did not reach levels of significance over the duration of the study (0.2 less than P less than 0.3).

Evaluation of cyclophosphamide, adriamycin, and cis-platinum (CAP) in patients with disseminated prostatic carcinoma. A phase II study.

A prospective study was conducted to evaluate response rate and toxicity of the combination of cyclophosphamide, adriamycin, and cis-platinum in patients with disseminated hormonally resistant prostatic carcinoma. Twenty-two patients were entered in the study: 19 were evaluable for response. One patient achieved partial remission while 14 (73%) had stable disease. Four patients had progressive disease. Patients with stable disease and partial remission had subjective improvement and survived significantly (p less than 0.03) longer than patients with progressive disease (58 weeks vs. 22 weeks). Toxicity was mainly hematological, and one patient died from sepsis secondary to leukopenia. Nausea and vomiting was moderate to severe, with one patient refusing cis-platinum for that reason. Renal toxicity was tolerable and reversible. Lack of good measurable disease makes generalization difficult, but pointers from animal models, along with the biological activity suggested by our results, make this a worthwhile combination to be considered for a trial in a larger population with measurable disease or in a randomized trial vs. the more effective single agent.

Computerized bone scan. A potentially useful technique to measure response in prostatic carcinoma.

Computerized bone scanning (CBS), a technique used to measure quantitative changes in bone scans, is described. Ten patients with histologically proven metastatic carcinoma of the prostate had sequential CBS performed. Good correlation was found between marked improvement in CBS (more than 50% average decrease in counts) and objective responses. Two patients had partial remission with more than 50% average decrease in uptake by prostatic cancer project criteria; both of them had good pain control. Three patients had worsening of their disease by CBS, which correlated with other parameters of disease progression (new lesions in bone survey, loss of weight and poor survival). In those patients with less than 50% average change the correlation is not so clear cut. An increase in percentage of uptake occurs in the first month after beginning of therapy, and no significant change is observed until 3 months. CBS is a technique that allows for objective measurement of quantitative changes in bone uptake, which is potentially useful for the evaluation of response to treatment in patients with metastatic bone disease from carcinoma of the prostate.

Hypercalcemia in head and neck carcinoma. Incidence and prognosis.

A retrospective review of all head and neck cancers seen between January 1, 1975, and September 1, 1981, at Harper-Grace Hospitals, Detroit, Michigan, was performed. Of 1438 patients with head and neck cancers, 41 (2.9%) had hypercalcemia (calcium greater than 11.0 mg%) during the course of their disease. The incidence of hypercalcemia by site was 13 of 351 (3.7%) larynx, 7/280 (2.5%) pharynx, 19/733 (2.6%) oral cavity (floor of mouth 4/171, tongue 9/209, tonsil 5/176, palate 1/95, other 0/82, 2/26 (7.7%) nasal cavity, and 0/48 salivary gland carcinomas. Chest radiograph results were positive for mass lesions in 17/35 (49%). Bone scans and/or x-ray results were positive in 15/31 (48%), negative in 16/31 (52%), and were not evaluated in 10 patients. Of five patients tested, all had inappropriately elevated serum parathyroid hormone (PTH) for their serum calcium level. The hypercalcemia was medically treated in 29/41 (70%), with return-to-normal calcium levels in 17/29 (59%). Twelve patients (30%) received only terminal care. Survival from the diagnosis of hypercalcemia ranged from 1 to 514+ days (mean, 80+ days; median 33 days). It is concluded that hypercalcemia is unusual in head and neck carcinoma. Furthermore, hypercalcemia frequently is a late manifestation and terminal event. Finally, hypercalcemia in some patients may be mediated by PTH production.

Mitoxantrone: modest activity in a phase II trial in advanced prostate cancer.

Thirty-seven patients with metastatic prostate cancer refractory to endocrine therapy were treated in a phase II trial of mitoxantrone. Starting doses were 12 and 10 mg/m2 iv every 21 days for good-risk and poor-risk patients, respectively. Of the 35 evaluable patients, two had objective partial regression and five had stable disease. Response duration ranged from 7 to 17+ months. The drug was very well tolerated by these elderly patients; myelosuppression was the major toxic effect. We conclude that mitoxantrone has modest activity and acceptable toxicity in patients with advanced prostate cancer.

Chemotherapy for nasopharyngeal carcinoma. A ten-year experience.

Seventeen patients, 14 after radiation therapy relapse, with measurable nasopharyngeal carcinoma were treated with chemotherapy. Remissions were observed in 9 of 17 (53%) with 3 complete (CR) and 6 partial responses (PR). Five (2 CR + 3 PR) of seven patients with lymphoepithelioma achieved remission, 4 (1 CR + 3 PR) of 8 with keratinizing squamous cell carcinoma, and 2 progressions with transitional cell carcinoma. Complete remissions were only achieved with CDDP-based combinations, with 2 of the 3 CR rendered histologically free of disease at the time of repeat biopsy of the tumor bed. Nasopharyngeal carcinoma is responsive to chemotherapy, even after radiation therapy relapse. The most effective chemotherapy combinations contain CDDP. Histologic differentiation did not appear to influence the frequency of remissions.

A randomized trial of the combination of cis-platinum, oncovin and bleomycin (COB) versus methotrexate in patients with advanced squamous cell carcinoma of the head and neck.

A prospective randomized trial was conducted at Wayne State University, Detroit, Michigan, to compare the efficacy of the combination of high-dose cis-diamminodichloroplatinum, Oncovin (vincristine) and bleomycin (COB) to that of weekly methotrexate (MTX) in the induction and maintenance of remission in patients with previously treated advanced squamous cell carcinoma of the head and neck. Complete response (CR) was observed in 11.1% of patients treated with COB and in 8.3% of patients treated with weekly methotrexate. The overall response rate (PR + CR) was 33.3% to methotrexate versus 40.7% to COB. This difference was not significant, nor was the survival of patients treated by either modality. Important variables affecting survival in this study proved to be good performance status (greater than or equal to 70) and response to therapy. Nausea and vomiting were the more common side effects of COB (56%), while hematologic toxicity was more frequent and more severe in the methotrexate arm (75%). Combination chemotherapy with COB is not more effective in producing response or prolonging survival than weekly methotrexate in patients with advanced head and neck carcinoma when both regimens are compared in a randomized study.

Adjuvant chemotherapy with cis-diamminodichloroplatinum II and 120-hour infusion 5-fluorouracil in Stage III and IV squamous cell carcinoma of the head and neck.

A prospective study was carried out to investigate the effectiveness and toxicity of three courses of combination high-dose bolus CDDP and 120-hour continuous infusion 5-FU every three weeks prior to definitive surgery and/or radiation therapy in 35 patients with locally advanced Stage III and IV squamous cell carcinoma of the head and neck. Twenty-two patients (63%) achieved a CR and 11 (31%) a PR after three cycles of chemotherapy, for an objective response rate of 94%. Toxicity was clinically acceptable. Nausea and vomiting occurred in 23 of 35 (66%) without any patients discontinuing therapy for this reason. Leukopenia in 13 (37%) and reversible azotemia in six (17%). Following three courses of chemotherapy, 13 patients had surgical resection and 12 patients had radiation therapy. Ten of these 35 patients had no pathologic evidence of cancer in the surgical specimen or preradiation therapy biopsy. Only two patients of those achieving a complete objective response have relapsed. However, the median follow-up has been short. The authors concluded that three courses of CDDP and 5-FU is a highly effective and safe adjuvant treatment in patients with advanced carcinoma of the head and neck.

cis-platinum and 5-fluorouracil as initial therapy in advanced epidermoid cancers of the head and neck.

A total of 44 patients with previously untreated Stage IV squamous cell carcinomas of the head and neck were treated with a combination of cis-platinum (100 mg/sq m) and 96-hour infusion of 5-fluorouracil (5-FU) (1,000 mg/sq m/day) in two courses or with cis-platinum (100 mg/sq m) and 120-hour infusion of 5-FU (1,000 mg/sq m/day) in three courses. In the 26 patients receiving the two course regimen, the tumor response rate was 88.5%. In five of the 26 patients complete disappearance of the tumor was achieved; partial remission was obtained in 18 of 26 patients. The main side effects were nausea and vomiting (70%), leukopenia (27%), and mild-to-moderate renal toxicity (27%). In the 18 patients who received the three course regimen of 5-FU and cis-platinum, there were 11 (61%) complete responses, 6 (33%) partial responses, and 1 (6%) minimal response. The incidence of complete response was increased with each course given. No added toxicity was observed with surgery or radiotherapy.

Clinical trial of cisplatin and 5-FU infusion as initial treatment for advanced squamous cell carcinoma of the head and neck.

Initial treatment with drug combinations that include cisplatin and bleomycin has been effective in reducing tumor in patients with previously untreated epidermoid cancers of the head and neck. Because of the threat of pulmonary complications from bleomycin, patients with poor pulmonary function were excluded from those studies. We conducted a trial using the combination of cisplatin (100 mg/m2) and a 96-hour infusion of 5-FU (1000 mg/m2/day) and achieved a response rate of 88.5% in 26 patients treated with two courses. Five of these patients had complete remissions and 18 had partial remissions. Nausea and vomiting (experienced by 70% of the patients) was the predominant toxic effect, and 26% experienced leukopenia. Although all patients were initially inoperable, six underwent resection following chemotherapy, and another six underwent resection after chemotherapy and irradiation. Two additional patients were treated with radiation therapy after clinically achieving complete remissions following chemotherapy, and another ten received X-ray therapy after chemotherapy. Cisplatin and 5-FU infusion are effective without being as toxic as bleomycin in patients with previously untreated advanced carcinoma of the head and neck.

Phase II evaluation of 4'-(9-acridinylamino)-methanesulfon-m--anisidine (AMSA) in patients with advanced head and neck cancers.

4-(9-Acridinylamino) methanesulfon-m-anisidine (AMSA) was evaluated in 26 patients with advanced head and neck cancer in a phase II study. All patients were previously treated with one or combinations of the three modalities, namely, surgery, radiation treatment, or chemotherapy. Among the 23 evaluable patients, 2 achieved a partial response, 4 a minimal response, 9 with stable disease, and 8 with disease progression. Side effects were mainly granulocytopenia with mild GI symptoms. AMSA may have activity in recurrent squamous cell cancers of the head and neck and further evaluation in previously untreated patients or combination of AMSA with other chemotherapeutic agents should be considered.

Phase II study of hexamethylmelamine for disseminated prostatic carcinoma.

Hexamethylmelamine (NSC-13875) was given to 15 patients with disseminated prostatic cancer in a daily x 21 schedule at 6-week intervals. The schedule was 320 mg/m2/day in four divided doses for good-risk patients and 240 mg/m2/day for poor-risk patients. No response was observed in 14 evaluable patients, but seven patients had stable disease. Limiting toxicity was nausea and vomiting which developed in 80% of the patients and it was the reason for discontinuation of therapy in one patient. Hematologic toxicity was acceptable, and occurred in 80% of the patients. Leukopenia was more frequent than thrombocytopenia, occurring in 80% and 20%, respectively. All patients had been previously treated with hormones, but 6/15 were never exposed to cytotoxic chemotherapy.

Carcinoma of prostate metastatic to breast.

Clinically diagnosed breast metastasis from prostatic carcinoma is rare. Primary breast carcinoma in patients with prostatic primary is also uncommon. Four patients who presented with breast malignancies in the course of their prostatic carcinoma are described. All but one of them had diffuse metastatic disease. Three of them were on estrogens at the time breast malignancy was diagnosed. Difficulties always arise in differentiating primary lesions from metastasis clinically and histopathologically. The development of histochemical methods for acid phosphatase, and the newest indirect immunofluorescent antibody technique, used in one of our patients, helped in making the differentiation between primary lesion and metastatic disease. Diagnosis of prostatic carcinoma metastatic to breast carries a poor prognosis, and may be an indication for aggressive therapy.

Ureteral obstruction secondary to metastatic breast carcinoma.

An uncommon manifestation of breast cancer is ureteral obstruction secondary to metastatic disease. Five patients who recently developed this complication from two to 20 years after the diagnosis of breast cancer are described. Only two of the five patients had urinary symptoms. All of the patients were older, postmenopausal females who had bone metastases and all had responded to previous hormonal manipulation. Bone scanning was useful in detecting unsuspected hydronephrosis in two patients. Retroperitoneal disease appears to be a complication of long standing breast cancer which is usually hormonally dependent. Routine examination of the bone scan for renal asymmetry may aid in the diagnosis, especially in asymptomatic patients.