Anibal Drelichman

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.

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 (⩾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.

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 > 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. Cancer 52:2261‐2263, 1983.

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.

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.

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. Cancer 53:1060‐1065, 1984.

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 < P < 0.3).

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.

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 cyclo-phosphamide, 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 < 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.