Biomedical subjects

D L Citrin

Publications and source records attributed to D L Citrin.

At least 19 recordsLinked to original sources

PubMed1991

A comparison of Zoladex and DES in the treatment of advanced prostate cancer: results of a randomized, multicenter trial.

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.

Aged↗

PubMed1991

Eastern Cooperative Oncology Group study 1879: mitotane and adriamycin in patients with advanced adrenocortical carcinoma.

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.

Adrenal Cortex Neoplasms↗

PubMed1987

Clodronate. A randomized study in the treatment of cancer-related hypercalcemia.

Malignancy-associated hypercalcemia is a common and recalcitrant problem. Current modes of therapy are often ineffective or prohibitively toxic. Clodronate disodium is a diphosphonate capable of inhibiting bone resorption resulting in a hypocalcemic effect. In this randomized, placebo-controlled study, we investigated the effect of hydration only (Rx-1) vs the effect of hydration plus either intravenously administered clodronate disodium, 4 mg/kg of body weight per day for three days (Rx-2) or intravenously administered clodronate disodium, 12 mg/kg of body weight given once only (Rx-3). By the third day of observation, Rx-2 produced a significant 2.8 mg/dL (0.70 mmol/L) reduction in serum calcium levels, whereas Rx-1 and Rx-3 did not produce a significant hypocalcemic effect when compared with baseline values. There were no toxicities observed. Intravenously administered clodronate appears to be an excellent agent for the acute treatment of malignancy-associated hypercalcemia.

Adult↗

PubMed1987

Zoladex: a sustained-release, monthly luteinizing hormone-releasing hormone analogue for the treatment of advanced prostate cancer.

Zoladex, a sustained-release luteinizing hormone--releasing hormone (LHRH) analogue administered by subcutaneous injection every 28 days, was evaluated at three dose levels in 46 men with untreated advanced prostate cancer. All three Zoladex doses yielded similar endocrinologic effects. After initial transient increases in serum luteinizing hormone, follicle-stimulating hormone, and testosterone concentrations, serum testosterone was suppressed uniformly to castration levels within 22 days. At a median follow-up of 41 weeks, Zoladex had maintained persistent suppression of serum testosterone. Measurements of serum Zoladex levels indicated that release of the drug from the injected depot was sustained over a period of 1 month and that there was no drug accumulation as evaluated over an initial 3-month period. No antibodies to Zoladex were detected. Tumor regression rates and side effects with Zoladex therapy were similar to those reported with daily injections of subcutaneous LHRH therapy. Signs and symptoms consistent with a brief tumor flare after the first injection of the LHRH analogue were noted in eight (17%) of the study entrants. Spinal cord compression was observed in two patients within 1 week from the onset of therapy. Zoladex is considered to be an effective, sustained-release LHRH analogue for the treatment of patients with prostate cancer.

Adenocarcinoma↗

PubMed1987

Maintenance etidronate in the prevention of malignancy-associated hypercalcemia.

Normocalcemic patients with cancer who had been successfully treated for an episode of hypercalcemia were enrolled in a randomized, multisite, double-blind, placebo-controlled trial designed to determine the efficacy of maintenance oral etidronate in preventing the recurrence of moderate to severe hypercalcemia (serum calcium level, greater than 11.5 mg/dL [greater than 2.87 mmol/L]). Ten (40%) of 25 etidronate-treated patients and 17 (46%) of 37 placebo-treated patients had recurrence of hypercalcemia within 150 days. Although patients taking etidronate had a longer time to the development of hypercalcemia (median, 55 days vs 28 days), this was not significantly different from the control group. The high attrition rate in this trial from hypercalcemia and other malignancy-related causes represents a major difficulty in conducting studies with agents that may require prolonged administration before producing a therapeutic effect.

Administration, Oral↗

PubMed1986

Estramustine affects bone mineral metabolism in metastatic prostate cancer.

A patient with metastatic prostate cancer is described where treatment with Adriamycin (doxorubicin) and estramustine produced severe hypophosphatemia (serum phosphate level, 1.2 mg/dl), which was reversible when treatment was discontinued. Previous studies have shown no effect of Adriamycin on serum phosphate levels. A retrospective study of serial serum chemistry values was done in 15 patients treated with estramustine. A significant fall in the serum phosphate level (mean, 0.8 +/- 0.3 mg/dl) was observed during the first 6 weeks of treatment. When compared with similar patients treated with bilateral orchiectomy, estramustine-treated patients had lower levels of serum calcium, fractional excretion of calcium, serum phosphate, and renal tubular threshold for phosphate reabsorption (TmPO4/GFR). Qualitatively similar but quantitatively smaller effects were also seen in a group of patients treated with diethylstilbestrol (DES) in a dose of 1 to 3 mg daily. Estramustine appears to have significant effects on bone mineral metabolism, particularly on renal phosphate handling resulting in significant hypophosphatemia. This is probably due to an estrogenic effect.

Adenocarcinoma↗

PubMed1985

A phase II study of high-dose estrogens (diethylstilbestrol diphosphate) in prostate cancer.

Twenty-five patients with metastatic prostate cancer resistant to primary hormone therapy, received high-dose intravenous diethylstilbestrol diphosphate (Stilphostrol [Miles Pharm], DES-P) in a Phase II study using established response criteria. Objective response rate was 17%, while 22% of the patients were subjectively improved. Moderate gastrointestinal toxicity was reported in 10 patients (40%). Thromboembolic complications were seen in 2 (8%). The role of high-dose Stilphostrol in the treatment of hormone-resistant prostate cancer is limited.

Acid Phosphatase↗

PubMed1984

Treatment of metastatic prostate cancer. An analysis of response criteria in patients with measurable soft tissue disease.

Evaluation of response to systemic therapy in metastatic prostate cancer is often difficult because of the infrequency of nonbony indicator lesions. The authors previously described a set of response criteria for Phase II and III studies which can be applied in patients with only bony disease. They have retrospectively evaluated response to Adriamycin (doxorubicin) and (5-fluorouracil) 5-FU in 38 patients with measurable soft tissue and visceral disease, using their response criteria for acid phosphatase and clinical status and standard definitions of response. No correlation was attempted for bone disease. Agreement between the results obtained with each system was good. Using this system of evaluating response, patients with metastatic prostate cancer with bone-dominant disease are eligible for Phase II and III studies.

Acid Phosphatase↗

PubMed1984

Decreased serum phosphate levels after high-dose estrogens in metastatic prostate cancer. Possible implications.

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.

Aged↗

PubMed1983

Chemohormonal therapy of metastatic prostate cancer. A pilot study.

Combined chemohormonal therapy of metastatic prostate cancer has not been previously evaluated in patients failing primary hormones (estrogens and/or orchiectomy). The combination of Adriamycin and high-dose diethylstilbestrol diphosphate (Stilphostrol) was studied in 19 heavily pretreated patients, to document toxicity and patient acceptability. Major toxicity was myelosuppression, cardiac failure and venous thrombosis. Clinical improvement was noted in 10/16 (63%) of evaluable patients. Patients with pre-existing cardiac disease or venous thrombosis are not suitable for this therapy.

Aged↗

PubMed1983

A study of cyclophosphamide, adriamycin, cis-platinum, and methotrexate in advanced transitional cell carcinoma of the urinary tract.

Twenty patients with locally advanced and/or metastatic transitional cell cancer of the urinary tract were treated with cyclophosphamide 500 mg/m2, Adriamycin (doxorubicin) 40 mg/m2 and cis-platinum (CDDP) 40 mg/m2 given every three weeks for 2 cycles, alternating with methotrexate 40 mg/m2 weekly for six weeks (CAP-M). Five of thirteen (38%) evaluable patients responded, with a significant prolongation of survival. Toxicity in 18 evaluable patients was mild to moderate. Methotrexate can be combined with CAP with significant reduction in dosage of cyclophosphamide, Adriamycin and CDDP and reduced toxicity, without major loss of efficacy. The precise role of methotrexate in combination chemotherapy of bladder cancer remains to be defined.

Aged↗

PubMed1982

A phase II evaluation of adriamycin and cis-platinum in hormone resistant prostate cancer.

Twenty-five patients with metastatic prostate cancer were treated with a combination of Adriamycin 50 mg/m2 and cis-platinum (CDDP) 50 mg/m2 every three weeks. Response was evaluated using radioisotope bone scan, serum acid phosphatase levels, and clinical status. Response rates of 6% bone, 21% acid phosphatase, and 24% clinical status were noted. Major toxicity was gastrointestinal (due to CDDP). Treatment was well tolerated even in patients with extensive bone metastases and prior irradiation. Using the response criteria described here, patients with metastatic prostate cancer without measurable soft tissue disease are eligible for Phase II and III study.

Acid Phosphatase↗

PubMed1982

Influence of non-specific immunologic factors on prognosis in advanced bronchogenic carcinoma.

Fifty-nine evaluable patients with stage III bronchogenic carcinoma, participating in a randomized clinical trial evaluating the effect of adjuvant immunotherapy with levamisole or BCG in the treatment of clinically advanced lung cancer, were studied for their immunocompetence by in vitro and in vivo assays. Immunological tests consisted of measurements of natural killer (NK) cell and killer (K) cell cytotoxicity, skin testing reactivity to recall antigens, absolute lymphocyte count, and serum immunoglobulin (Ig) levels. Pretherapy K cell cytotoxic levels, skin test reactivity to trichophyton antigen, and increased IgA levels were predictive of the overall clinical course. Despite non-specific immunotherapy, progressive decline of NK and K cell cytotoxicity occurred during the course of the disease. These findings, however, were of limited clinical value. Initial performance status and disease extent significantly influenced time to progression and survival. Little further prognostic information was obtained from the immunological tests over those provided by clinical performance status and disease extent. No statistically significant differences were found in either time to progression or survival between controls and patients receiving either levamisole or BCG.

Carcinoma, Bronchogenic↗

PubMed1981

The use of serial bone scans in assessing response of bone metastases to systemic treatment.

The accuracy levels of serial radioisotope bone scans and conventional bone radiographs in assessing the response of bone metastases to systemic therapy were compared in 34 women with metastatic breast cancer. Each patient had measurable or evaluable nonosseous metastases, which were assessed independently of skeletal disease. The bone scan was found to be more accurate and sensitive indicator of the status of bone metastases than the radiograph. The bone scan correlated well with response of soft tissue or visceral disease, while the results of repeated bone radiographs were frequently misleading. With use of a digital model, it was possible to accurately measure the area of skeletal involvement of the bone scan, and from this derive quantitative criteria for response in bone metastases analogous to response criteria currently in use for soft tissue and visceral disease. It is suggested that serial quantitative bone scans be done, in preference to radiographs, to assess the response of bone metastases to systemic therapy.

Adult↗

PubMed1981

Systemic treatment of advanced prostatic cancer: development of a new system for defining response.

The low incidence of measurable or evaluable metastases in patients with prostatic cancer makes evaluation of response difficult. This is particularly true in patients with bone metastases only. With a digital model it is possible to measure quantitatively from the radioisotope bone scan the total area of skeletal involvement by metastatic tumor. Definitions of response in bone have been derived from this model. These response criteria have been compared to response in acid phosphatase determinations and clinical status in a study of 44 patients with advanced prostatic cancer treated with estramustine phosphate. Based on serial quantitative bone scans, serial measurements of acid phosphatase levels and repeat clinical evaluations a system is proposed for defining response to systemic therapy that is applicable to the majority of patients with metastatic prostatic cancer.

Acid Phosphatase↗

PubMed1980

Hyperaldosteronism associated with liver metastases.

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.

Aldosterone↗

PubMed1980

A clinical and pathological study of adrenocortical carcinoma: therapeutic implications.

Twenty-one patients with adrenocortical carcinoma (ACC) diagnosed at three hospitals over a ten-year period were reviewed for clinical and pathologic features that might have therapeutic implications. Depending upon the extent of cellular pleomorphism, ACC could be defined as anaplastic or differentiated. Anaplastic ACC occurred more often in male patients, produced more frequent cutaneous metastases (P = 0.01), and was associated with a lack of clinical or laboratory evidence of hormone production (P = 0.01). In contrast, differentiated ACC usually occurred in women and produced clinical or laboratory evidence of hormonal excess. Median survival time of patients with anaplastic ACC was only five months, while median survival time of those with differentiated ACC was 40 months (P = 0.005). Patients with differentiated ACC survived for long periods, even with metastatic disease. Three of 5 such patients had objective responses to o,p'-DDD (Mitotane) therapy. The histopathology of ACC is an important prognostic factor and should be considered in the design of future therapeutic trials.

17-Ketosteroids↗

PubMed1980

Adriamycin enhancement of cyclophosphamide-induced bladder injury.

Hemorrhagic cystitis as a complication of cancer chemotherapy has been most commonly associated with cyclophosphamide. We report on a patient who had received cyclophosphamide for treatment of breast carcinoma and had hemorrhagic cystitis temporally associated with subsequent adriamycin therapy. The development of subclinical bladder injury induced by cyclophosphamide and enhanced by adriamycin similar to their combined toxicities at other sites (skin, esophagus and heart) is postulated.

Breast Neoplasms↗