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Menogaril is a semisynthetic anthracycline that is less cardiotoxic than doxorubicin in a preclinical model. We conducted a phase II trial to determine the activity of menogaril in hormone-refractory prostate cancer. Between October 1985 and November 1987, 32 eligible patients were enrolled and were divided into good- and poor-risk categories, the latter being defined by prior radiotherapy to less than one third of the marrow-containing skeleton. Good-risk patients received a starting dose of 200 mg/m2 by 60-minute IV infusion, whereas the poor-risk patients received 160 mg/m2. Treatment was repeated every 3 weeks until disease progression. Menogaril caused leukopenia in 90% of patients, of whom 47% had grade III or IV toxicity. Thrombocytopenia was uncommon and mild, with only three patients (9%) experiencing grade II toxicity. Nonhematologic toxicity included mucositis (9%), and mild weight loss in 33% of patients. Nine patients (28%) had stable disease of 3 or more months' duration. There were no objective partial or complete responses. The median time to progression for the entire group was 10 weeks, and the median survival time for all patients was 24 weeks. Because of appreciable toxicity and limited antitumor activity, further study of menogaril cannot be recommended in hormone-refractory prostate cancer.

Twenty-nine patients with progressive hormone-refractory metastatic adenocarcinoma of the prostate were treated with daily estramustine phosphate at 10 mg/kg, and I.V. doxorubicin 50 mg/m2 every 3 weeks. Twenty-six patients were evaluable. Four of seven patients with nonosseous measurable disease had partial responses lasting 3 to 10 months. Eleven of 19 patients with osseous metastases had stable disease or improvement on bone scan, 6 of these for 7 months or longer. Median time to progression was 20 weeks, and the median survival was 43 weeks.

From November 1979 to July 1986, 52 patients (27 women and 25 men; median age 52 years) with advanced adrenocortical carcinoma entered a prospective, nonrandomized study evaluating moderate-dose mitotane and doxorubicin hydrochloride (Adriamycin). Thirty-two tumors (62%) were well differentiated and evidence of hormone production was present in 24 patients (46%). Patients with well-differentiated or functional tumors received mitotane, 6 gm daily; patients for whom mitotane failed or those with poorly differentiated, non-hormone-producing tumors received Adriamycin, 60 mg/m2 every 3 weeks. Initially, 36 patients were treated with mitotane and 16 patients with Adriamycin. Eight patients (22%) responded to mitotane and three (19%) responded to Adriamycin. No response was noted in the 15 patients for whom mitotane failed and who then received Adriamycin. Severe toxicity occurred in 36% of patients who received mitotane and in 26% who received Adriamycin. Overall median survival after onset of treatment was 14 months. We conclude that mitotane or Adriamycin used initially can induce tumor regression in about 22% and 19% of selected patients, respectively. However, Adriamycin is ineffective as second-line chemotherapy for patients with well-differentiated or functioning tumors for whom mitotane is ineffective.

This open, prospective study was conducted to compare ZOLADEX (goserelin acetate implant) and diethylstilbestrol (DES) in the treatment of stage D2 prostate cancer. Sixty-seven patients were allocated to receive 3.6 mg of ZOLADEX every 28 days by subcutaneous injection (n = 48) or 3 mg of DES daily by oral administration (n = 19). Median serum levels of testosterone were reduced to castrate levels (less than 50 ng/dl) within one month of therapy in each group and remained so for up to 120 weeks. According to modified criteria of the National Prostatic Cancer Project, 88% of patients in the ZOLADEX group and 84% in the DES group were objective responders. Time to treatment failure and survival were not significantly different between groups, yet the confidence limits for the hazard ratios were wide. ZOLADEX was better tolerated than DES. We conclude that ZOLADEX is an alternative to DES in patients with stage D2 prostate cancer.

Hypophosphatemia and osteomalacia have been described in patients with metastatic prostate cancer. The mechanism of hypophosphatemia in prostate cancer is not known. A decrease in serum phosphate levels was observed in 16 of 18 patients with metastatic prostate cancer treated with high-dose diethylstilbestrol diphosphate. To determine if the fall in serum phosphate was indeed due to diethylstilbestrol diphosphate, the data from several similar groups of patients treated with chemotherapy and combined chemohormonal therapy that included diethylstilbestrol diphosphate were re-examined. Fifty-eight patients were treated with doxorubicin, doxorubicin plus cis-platinum, doxorubicin plus diethylstilbestrol diphosphate, or diethylstilbestrol diphosphate alone. A significant decrease in serum phosphate levels was seen only in patients treated with diethylstilbestrol diphosphate. Hypophosphatemia and possibly osteomalacia in metastatic prostate cancer may be related to estrogen therapy.

Seventy-five female patients with early primary cancer of the breast were studied by bone scanning with 99mTc labeled phosphate at the time of initial presentation and serially during follow-up examination. Eleven patients had an abnormal bone scan at the time of presentation. During follow-up periods, which have ranged from three to 34 months with a mean of 16 months, abnormal bone scans have developed in a further 13 patients. To date, nine of the 24 patients with an abnormal bone scan have died, while only one of the 51 with a persistently normal scan has died. It is concluded that an abnormal bone scan carries a significant risk of earlier death due to metastatic disease.

Plasma aldosterone levels were measured in 50 patients with confirmed liver metastases from various histologically proved primary tumors. None of these patients had electrolyte abnormalities or history of benign liver disease, congestive heart failure, hypertension, or renal disease. Patients with edema, ascites, or both had significantly greater elevation of plasma aldosterone levels compared to nonedematous patients; these patients also demonstrated a substantial degree of hepatic dysfunction as evidenced by lower serum albumin levels and higher bilirubin and alkaline phosphatase levels. This study provides a rational basis for the use of the specific aldosterone inhibitor spironolactone in the treatment of patients with advanced metastatic liver disease and edematous states.

Certain easily recognisable features are commonly seen in the bone scans of patients with metabolic bone disorders. Seven such features have been numerically graded by three independent observers in the scans of 100 patients with metabolic bone disease and of 50 control subjects. The total score for each patient is defined as the metabolic index. The mean metabolic index for each group of patients with metabolic bone disease is significantly greater than that for the control group (P less than 0.001).

The usefulness of plasma ribonuclease assays was studied in (i) patients with possible protein deficiency, (ii) patients with myelomatosis, (iii) patients with carcinoma of the breast. In each group, the major factor associated with elevation of plasma ribonuclease was impairment of renal function. The assay was therefore of little value in the assessment of patients with myelomatosis or carcinoma of the breast. However, in the patients with possible protein deficiency and normal renal function, an elevation of plasma ribonuclease is, in general, associated with a decrease in serum albumin, transferrin and cholinesterase. Plasma ribonuclease may therefore be a useful parameter in the assessment of protein nutritional status.