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Biomedical subjects

J Aisner

Publications and source records attributed to J Aisner.

At least 109 records · Page 6Linked to original sources
PubMed1986

Phase I clinical and pharmacokinetic study of cyclophosphamide administered by five-day continuous intravenous infusion.

A total of 14 patients, 7 male and 7 female, received in all 21 evaluable courses of cyclophosphamide administered by 5-day continuous infusion. Cyclophosphamide doses were escalated from 300 to 400 mg/m2 per day for 5 days and repeated every 21-28 days. The patient population had a median age of 55 years (range 38-76) and a median Karnofsky performance status of 80 (range 60-100). Only 1 patient had not received prior therapy; 5 patients had received only prior chemotherapy, 1 had received only prior radiotherapy, and 7 had received both. Tumor types were gastric (1), lung (2), colon (4), urethral adenocarcinoma (1), cervical (2), chondrosarcoma (1), melanoma (1), uterine leiomyosarcoma (1), and pancreatic (1). The dose-limiting toxicity was granulocytopenia, with median WBC nadir of 1700/microliter (range 100-4800) in 8 heavily pretreated patients treated at 350 mg/m2 per day for 5 days. One patient without heavy prior treatment received two courses at 400 mg/m2 and had WBC nadirs of 800/microliter and 600/microliter. WBC nadirs occurred between days 9 and 21 (median 14). Drug-induced thrombocytopenia occurred in only one patient (350 mg/m2 per day, nadir 85,000/microliter). Neither hyponatremia nor symptomatic hypo-osmolality was observed. Radiation-induced hemorrhagic cystitis may have been worsened in one patient. Nausea and vomiting were mild. Objective remissions were not observed. The maximum tolerated dose for previously treated patients is 350 mg/m2 per day for 5 days. This dose approximates the doses of cyclophosphamide commonly used with bolus administration. Plasma steady-state concentrations (Css) of cyclophosphamide, measured by gas liquid chromatography, were 2.09-6.79 micrograms/ml. Steady state was achieved in 14.5 +/- 5.9 h (mean +/- SD). After the infusion, cyclophosphamide disappeared from plasma monoexponentially, with a t 1/2 of 5.3 +/- 3.6 h. The area under the curve of plasma cyclophosphamide concentrations versus time (AUC) was 543 +/- 150 micrograms/ml h and reflected a cyclophosphamide total-body clearance (CLTB) of 103 +/- 31.6 ml/min. Plasma alkylating activity, assessed by p-nitrobenzyl-pyridine, remained steady at 1.6-4.3 micrograms/ml nor-nitrogen mustard equivalents. Urinary excretion of cyclophosphamide and alkylating activity accounted for 9.3% +/- 7.6% and 15.1% +/- 2.0% of the administered daily dose, respectively. The t1/2 and AUC of cyclophosphamide associated with the 5-day continuous infusion schedule are similar to those reported after administration of cyclophosphamide 1500 mg/m2 as an i.v. bolus.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Phase I trial of 5-day continuous infusion aziridinylbenzoquinone (AZQ, diazaquone, NSC 182968).

AZQ was given to 14 patients with solid tumors in a phase I trial. Eight males and six females with a median Karnofsky performance status of 70% (range 40-90%) and a median age of 64 years (range 24-72) received 18 evaluable courses. All patients received prior chemotherapy and seven had prior irradiation. A continuous infusion for 5 consecutive days at doses of 4-8 mg/m2 per day was given every 3-4 weeks. Dose-limiting toxicity was myelosuppression, especially thrombocytopenia. No patient developed an infection while on this study. There was no evidence of cumulative toxicity in the three patients receiving two or more courses. Nonhematologic toxicity consisted only of mild nausea and vomiting in three patients and mild diarrhea in two patients. No patient experienced any mucosal, hepatic, renal, cardiac, or central nervous system toxicity. No objective antitumor responses were seen in the three patients with measurable disease who received two or more courses of AZQ. The recommended doses for phase II studies for continuous-infusion AZQ are 6 mg/m2/day X 5 repeated every 4 weeks.

Adult↗
PubMed1986

Treatment approaches for lung cancer patients in a community hospital.

During the past decade, a number of new and successful treatments for cancer have been introduced at many cancer centers. During the same period, increasing numbers of cancer patients were treated outside of major cancer centers (i.e., in the community hospital) by an expanding number of trained oncologists. However, it is unclear to what extent new therapeutic approaches have been adopted in the community hospital setting. Recent studies have raised important questions about the patterns of treatment of patients outside of cancer centers. The present study was undertaken to describe the processes of treatment for lung cancer patients in a 514-bed community hospital in a metropolitan area. The study sample consisted of all patients with lung cancer entered into the hospital's tumor registry during 1980 and 1981 (n = 147). Medical oncologists were consulted regarding the care of a large number of patients, particularly those with small cell carcinoma for whom medical oncologists can offer therapy which has been demonstrated to be effective. As judged by patients with small cell carcinoma, patients are being treated appropriately, for the most part, with chemotherapy. Fourteen percent of all patients received no treatment for their cancer, and this may be a source of concern. Future research in this area should be directed at conducting similar studies in smaller hospitals, comparing the quantity and quality of survival for patients treated in various types of settings, and assessing the determinants of processes of care (e.g., no treatment) in various treatment settings.

Adult↗
PubMed1986

CT evaluation of patients during treatment of advanced non-small cell lung carcinoma.

Twenty-one patients with Stage III non-small cell bronchogenic carcinoma were studied by chest radiograph and computed tomography (CT) before and after chemotherapy. In three patients (14%), the prechemotherapy CT showed measurable disease not seen on chest radiograph. Postchemotherapy CT scans showed additional measurable disease not seen on chest x-ray films in nine of 56 (16%) follow-up exams. This represented additional disease in seven of the 21 patients (33%). The CT findings resulted in a significant change in therapy in six of the 21 patients (29%).

Adult↗
PubMed1986

Special studies of the Hickman catheter of a patient with recurrent bacteremia and candidemia.

A patient with acute non-lymphocytic leukemia developed Staphylococcus epidermidis bacteremia and candidemia after maintenance chemotherapy and was treated satisfactorily. He returned 3 months later with abdominal pain due to an abdominal aortic aneurysm. At laparotomy, the aneurysm was found to be infected with Candida albicans. Following surgery, repeated positive blood cultures for C. albicans led to removal of his Hickman catheter. Culture of the catheter tip yielded C. albicans and S. epidermidis. Study of the catheter by scanning and transmission electron microscopy demonstrated yeast-like cells and gram-positive cocci in a biofilm. These studies suggest that the Hickman catheter was the source of the persistent candidemia and that it may have been the origin of the infection of the aneurysm.

Antineoplastic Agents↗
PubMed1986

High-dose chemotherapy without autologous bone marrow transplantation in melanoma.

High-dose chemotherapy with BCNU, melphalan, or both, followed by autologous bone marrow transplantation (ABMT) has been reported to produce response rates in excess of 60% in patients with advanced melanoma. We tested doses of BCNU associated with reversible bone marrow toxicity and acceptable extramedullary toxicity without the use of ABMT in 19 patients with a diagnosis of advanced malignant melanoma. All patients were evaluable for toxicity and 18 were evaluable for response; one patient had a new primary tumor. The patient population had a median age of 44 years (range, 16 to 71) and a median Karnofsky performance status of 80 (range, 50 to 100). Ten were women and nine were men, all had visceral dominant disease, and none had received previous chemotherapy. Our purpose was to test the feasibility of treatment without ABMT, its toxicity and efficacy, and the possibility of administering sequential repeated courses of therapy. Vincristine was added to the regimen to potentially increase efficacy. Treatment consisted of BCNU (750 mg/m2) and vincristine (2 mg days 1 and 8). Six patients who recovered bone marrow function received melphalan (60 mg/m2) and vincristine (2 mg days 1 and 8). Twenty-two percent (95% confidence limits, 3% to 39%) of patients had remissions (all partial) and these were of short duration. Toxicity was substantial with 16% early lethality and 29% incidence of lethal drug-related complications. Two patients (11%) died toxic after a second course of BCNU. Our results suggest that there is no practical role for high-dose BCNU in the treatment of melanoma.

Adolescent↗
PubMed1986

Human plasma pharmacokinetics and urinary excretion of thiotepa and its metabolites.

Thiotepa has been used clinically for greater than 30 years but its pharmacokinetics remain poorly defined. We determined the plasma pharmacokinetics and urinary excretion of thiotepa and its metabolites in 21 patients with breast cancer who received 25 courses of iv bolus thiotepa (12 mg/m2) as part of combination chemotherapy. Plasma samples were obtained before injection: at 5, 10, 15, 30, 45, 60, 90, and 120 minutes; and, when possible, 180 and 240 minutes after injection. In eight courses, urine was collected as 4-hour aliquots for 24 hours after therapy. All samples were analyzed for thiotepa and tepa by gas-liquid chromatography. Urinary alkylating activity was assessed spectrophotometrically after reaction with 4-(p-nitrobenzyl)-pyridine. Plasma concentrations of thiotepa declined in a biexponential fashion with an alpha-half-life of 7.7 +/- 1.2 minutes and a beta-half-life of 125 +/- 21 minutes. Total-body clearance of thiotepa was 186 +/- 20 ml/minute/m2. The volume of the central compartment was calculated as 0.25 +/- 0.04 L/kg, and the steady-state volume of distribution was calculated as 0.70 +/- 0.11 L/kg. Tepa was detectable in plasma by 5 minutes after the injection of thiotepa. Tepa concentrations increased from 0.093 +/- 0.068 to 0.127 +/- 0.11 micrograms/ml over the 240-minute collection period. By 120 minutes, the concentration of tepa equaled that of thiotepa, and tepa persisted longer in the plasma than did thiotepa. During the first 24 hours after injection, urinary excretion of thiotepa, tepa, and alkylating activity accounted for 1.5%, 4.2%, and 23.5% of the administered dose, respectively. These results extend our laboratory's previous animal studies of thiotepa and argue for metabolism of thiotepa to tepa as a major mechanism of clearance of this compound. Further metabolism or breakdown of both compounds may explain the urinary excretion of alkylating materials other than parent compound and tepa.

Adult↗
PubMed1986

Human pharmacokinetics, excretion, and metabolism of the anthracycline antibiotic menogaril (7-OMEN, NSC 269148) and their correlation with clinical toxicities.

In a Phase I study, menogaril (7-OMEN) was administered daily for 5 days/course, every 21-28 days. Dosages of 3.5, 7, 11.5, 17, and 31.5 mg/m2 were infused over 1 h, and dosages of 42, 50, and 56 mg/m2 were infused over 2 h. Pharmacokinetics was studied at all dosages. Plasma and urine samples were collected from 24 patients, and bile samples were also collected from 2 patients. 7-OMEN and metabolites were measured by high performance liquid chromatography. 7-OMEN was the major plasma fluorescent species at all times, with only trace amounts of N-demethyl menogaril observed. 7-OMEN disappeared from plasma biexponentially with t1/2 alpha 0.19 +/- 0.04 (mean +/- SE) h and t1/2 beta 13.22 +/- 1.54 h. Plasma pharmacokinetics of 7-OMEN was linear from 3.5-56 mg/m2; area under the curve increased proportionally with dosage. Total body clearance of 7-OMEN was 28.18 +/- 3.33 liter/m2/h, Vc was 224 +/- 30.8 liter/m2, and Vss was 370 +/- 25.7 liter/m2. Plasma pharmacokinetics of 7-OMEN studied on multiple days of a given course were similar. Urinary excretion of 7-OMEN and fluorescent metabolites accounted for 5.4 +/- 0.4% of the daily dose. Parent compound still represented greater than or equal to 80% of urinary drug fluorescence after 24 h. N-demethyl menogaril was the only other fluorescent drug species detected in urine. In two patients with biliary tract drains, biliary excretion of drug fluorescence accounted for 2.2-4.2% of the daily dose. Only 7-OMEN and N-demethyl menogaril were detected in bile by high performance liquid chromatography and thin layer chromatography. 7-OMEN was the major fluorescent biliary species, but, by 24 h, N-demethyl menogaril accounted for approximately 40% of biliary drug fluorescence. When considered in light of each patient's observed toxicities, excellent relationships were observed between the plasma area under the curve of 7-OMEN and the percentage of decreases in WBC and absolute neutrophil count. These latter findings should be useful in developing more precise and intelligent dosing schemes for 7-OMEN.

Antineoplastic Agents↗
PubMed1986

Phase I trial of menogaril administered as an intermittent daily infusion for 5 days.

Menogaril, a semisynthetic derivative of nogalomycin, was brought to phase I clinical testing in patients with refractory solid tumors. Twenty-seven patients received 50 evaluable courses. Menogaril was given as a 1-2-hour iv infusion on 5 consecutive days, with courses repeated every 4 weeks, provided there was reversal of all drug-related toxic effects. The starting dose was 3.5 mg/m2/day X 5, with escalations in subsequent cohorts of patients to 56 mg/m2/day X 5. Neutropenia was dose dependent and dose limiting. At 56 mg/m2/day X 5, the median wbc count nadir was 1100/microliter, and two of four patients were hospitalized for fever and suspected bacteremia. At 50 mg/m2/day X 5, the wbc count nadir was 2300/microliter. Platelet toxicity was less severe. Nonhematologic toxicity consisted primarily of local urticaria and moderate to severe phlebitis at the infusion site, which were dose dependent and lasted up to 6 weeks. For phase II studies, the recommended dose of menogaril is 50 mg/m2/day for 5 consecutive days administered as a 2-hour intermittent infusion, repeated every 28 days.

Adult↗
PubMed1986

Doxorubicin, cyclophosphamide, etoposide and platinum, doxorubicin, cyclophosphamide and etoposide for small-cell carcinoma of the lung.

Small-cell lung cancer (SCLC) is a disseminated disease regardless of our ability to document all sites. Chemotherapy is thus the cornerstone of treatment. There are multiple active single agents, resulting in many combination chemotherapy regimens. Optimal combinations are probably derived from the use of synergistic drug interactions. A three drug combination of doxorubicin (Adriamycin), cyclophosphamide, and etoposide (ACE) has been used at the University of Maryland Cancer Center (UMCC) for more than a decade in sequential studies. Two hundred four patients, 143 men and 61 women, were treated on these studies. Eighty-five had limited disease (LD) and 119 had extensive disease (ED). The complete response (CR) frequencies were 65% and 43% for LD and ED, respectively, and the median survivals were 15 and 9.5 months, respectively. Twenty-two percent of the LD patients were alive at 2 years. To improve upon response or survival, and because of synergy, cisplatin was added to ACE (PACE). PACE chemotherapy was administered in two studies--study 1 at UMCC for both LD and ED, and study 2 by Cancer and Acute Leukemia Group B (CALGB) for ED only. Preliminary review suggests that CR frequencies for LD (53%, study 1) and ED (44%, study 1; 37%, study 2) were similar to prior studies, but median survivals (LD, 18+ months, study 1; ED, 15 months, study 1, 10.5 months, study 2) appears superior to previous studies. However, PACE is more toxic than ACE. Further studies of PACE are needed to assess if the additional toxicities are warranted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Performance status assessment among oncology patients: a review.

Performance status is a global assessment of a patient's ability for self-care and ambulation. It is an important and widely used prognostic variable for patients with cancer. Several different scales to assess performance status are in use, and scale scores are used for a variety of purposes, including patient selection and stratification for cancer clinical trials. New uses for life quality evaluations have also been proposed. Despite the widespread use of the scales, little information is available about the reliability and validity of these measures. Improved and extended application of these scales requires that several types of data about measurement properties of the scales be collected and analyzed. Various issues related to the measurement properties of the scales and their implications for oncology need to be understood to best develop their use.

Clinical Trials as Topic↗
PubMed1986

Antiemetic studies: a methodological discussion.

Methodological issues encountered in reviewing the antiemetic literature are discussed. Variables affecting antiemetic assessment include those relating to the patient, the emetic stimulus, and the differences in action of the antiemetic drugs. Study design questions including the desirability of randomization, double blinding, use of controls, and stratifications for factors such as previous exposure to chemotherapy and strength of the emetic stimulus are discussed. From a statistical viewpoint a parallel subject design with adequate sample size is recommended. The problems of standardizing the evaluation of nausea and vomiting are considered and simple ordinal scales grading severity are suggested. The patient's overall assessment of tolerance of therapy is of primary importance.

Antiemetics↗
PubMed1986

High-dose megestrol acetate in the treatment of postmenopausal women with advanced breast cancer.

The optimal dose of progesterone compounds for the treatment of breast cancer is unknown, but there is evidence to suggest a dose-response curve. We are testing the tolerability and efficacy of megestrol acetate administered orally and continuously in doses three to ten times higher than the standard dose of 160 mg/d. We have so far treated 33 patients with metastatic breast cancer and positive or unknown tumor hormone receptor status. Thirty patients had had documented disease progression with previous hormonal therapy, and 22 had failed with previous chemotherapy. Twenty-five patients had objectively measurable metastases. In this heavily pretreated group, the objective response rate was 40%; in addition, 32% of patients had stabilization of disease. Interestingly, ten of 12 patients who had developed disease progression while on standard-dose megestrol acetate therapy had objective response or stabilization on the higher dose. Toxicity was acceptable and reversible and included mild elevations of blood pressure and weight gain. Our results indicate that high-dose megestrol acetate is well-tolerated and highly active in advanced refractory breast cancer, and suggest a dose-response curve for the drug in the treatment of breast cancer.

Adult↗
PubMed1986

Appetite stimulation with megestrol acetate in cachectic cancer patients.

Cachexia is often a severe problem in the management of cancer and other illnesses because it adds to the morbidity of the underlying disease and complicates its treatment. Megestrol acetate has been observed anecdotally to produce weight gain. A review of our experience, and our ongoing phase I/II study of high-dose megestrol acetate for breast cancer, revealed that weight gain occurred in nearly one third (27%) of patients at conventional doses (160 mg/d), and that a marked weight gain (median, 5.1 kg; range, 0.9 to 20.1 kg) occurred in 27 of 28 patients with breast cancer during treatment with high doses of megestrol acetate. Subjective improvement in appetite occurred in most patients at low doses and in most patients at high doses. Further, nearly one half (48%) of patients at conventional doses and virtually all patients at high doses experienced an increased sense of well-being. Our data suggest that megestrol acetate has a potential role in producing subjective improvement, sense of well-being, and increase in appetite and weight, and that the effect may be dose related. Further research is necessary to understand the mechanism of appetite stimulation and/or anabolic effect.

Adult↗
PubMed1985

Vindesine and high-dose cisplatin in the treatment of advanced non-small-cell lung cancer.

Seventeen patients with advanced non-small-cell lung cancer (NSCLC) were entered on a combination chemotherapy protocol including vindesine and high-dose cisplatin. All patients had measurable disease and had not previously received chemotherapy. All patients entered were evaluable for toxicity and response. Tumor regression was limited to one complete and one partial response (response rate, 11.7%; 95% confidence limits, 0 to 27%). The complete and partial response lasted 260 + and 82 days, respectively. For the 15 nonresponding patients, the median time to disease progression was 76 days. Median survival was 141 days for the whole group. Significant toxic effects were vindesine-related peripheral neuropathy and cisplatin-induced emesis. Myelosuppression was mild and manageable. The response for the vindesine-cisplatin combination observed in our study is inferior to that seen in a previous vindesine-cisplatin trial reported by others. Thus, the true value of this two-drug regimen in the treatment of NSCLC remains to be established.

Adenocarcinoma↗
PubMed1985

Training and oncologists' changing attitudes toward their own cancer therapy.

Oncologists' attitudes toward therapy for his or her own hypothetical cancer have not been studied, and they may influence therapeutic decisions for patients. This study compared attitudes of oncologists at different levels of training toward therapy for their own hypothetical cancer. Those with limited oncology experience had high expectations for treatment, as expressed in their acceptance of all therapeutic modalities for their own disease. Early intensive inpatient oncology experience (first year of training) led to disenchantment, and rejection of various therapies. Further outpatient experience led to an increased acceptance of therapy again, and those finishing second and third year of oncology training, and senior medical staff in oncology, had high expectations for treatment. These results suggest an evolution of attitudes toward therapy with training and experience.

Attitude of Health Personnel↗
PubMed1985

A case report and description of the pharmacokinetic behavior of intrapleurally instilled etoposide.

Etoposide, at a dosage of 100 mg/m2 (156 mg in 250 ml 0.154 M NaCl), was instilled through a thoracostomy tube into the left pleural cavity of a 60-year-old woman with diffuse histiocytic lymphoma and a refractory, recurrent, malignant left pleural effusion. Etoposide concentrations in plasma and pleural cavity fluid were measured by a reverse-phase HPLC system with a C18-reverse phase column, a mobile phase of methanol: H2O (55:45) pumped at 1.2 ml/min, and detection by absorbance at 254 nm. Pleurodesis was successfully accomplished by this maneuver and there were no adverse clinical consequences. Absorption of etoposide from the pleural cavity was slow (approximately 0.2 ml/min). The pleural cavity exposure to etoposide, as measured by the area under the curve, was 46 times greater than if a similar dose had been given IV. Conversely, systemic exposure to etoposide, as assessed by plasma AUC, was less than 50% that associated with IV injection of a similar dose.

Absorption↗