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Biomedical subjects

S B Kahn

Publications and source records attributed to S B Kahn.

At least 19 recordsLinked to original sources

N-Methylformamide in advanced squamous cancer of the uterine cervix: an Eastern Cooperative Oncology Group phase II trial.

PURPOSE: Preclinical and clinical data support the study of polar-planar compounds such as N-Methylformamide (NMF) in advanced squamous cell carcinoma of the uterine cervix (SCC). This phase II trial sought to determine the efficacy and toxicities of NMF in patients with advanced SCC. PATIENTS AND METHODS: Eligibility for this trial required bidimensionally measurable squamous or adenosquamous cell cancer of the uterine cervix incurable by surgery or radiation therapy, ECOG performance status of < or = 2, no prior NMF and no more than one prior chemotherapy regimen. Patients received NMF at 2000 mg/m2 intravenously over 15-30 minutes days 1, 8 and 15. The cycle was repeated every 42 days. A single dose escalation of 25%, 500 mg/m2 was made after the first cycle if the toxicities did not exceed grade I for hepatic toxicity and grade II for nausea and vomiting. RESULTS: From July 1987 through September 1998, 21 patients with advanced squamous cell carcinoma of the uterine cervix were entered on study. Two patients were ineligible because there was no pretreatment SGOT on one and the other deteriorated prior to drug approval. Therefore, 19 patients were include in the analysis of response and survival. Four were inevaluable, three due to inappropriate tumor evaluation and one secondary to grade III vomiting, who went off study. These patients were included in the denominator while computing the results. There were 2 deaths, one due to pulmonary hemorrhage from perforation during central venous insertion and one due to disease. 30% (6/19) patients had toxicities, Eastern Cooperative Oncology Group (ECOG) grade III or higher and 2 of these patients suffered multiple grade III toxicities. There were no complete or partial responses. CONCLUSION: In this population, NMF in the dose and schedule employed exhibited no clinical activity.

Aged↗

Use of granulocyte colony-stimulating factor after high-dose chemotherapy and autologous peripheral blood stem cell transplantation: what is the optimal timing?

Administration of granulocyte colony-stimulating factor to patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation accelerates neutrophil recovery and decreases hospitalization time. The optimal timing for granulocyte colony-stimulating factor infusion remains unknown. In this retrospective, case-controlled, two-armed study, we reviewed our experience at Hahnemann University Hospital to determine whether initiating granulocyte colony-stimulating factor infusions on posttransplant day 0 versus day 8 affects neutrophil recovery time, posttransplant discharge date, total hospital days after high-dose chemotherapy, and autologous peripheral blood stem cell transplantation. All patients hospitalized between 1994 and 1998 at Hahnemann University Hospital, Bone Marrow Transplantation Unit with breast cancer or non-Hodgkin's lymphoma, who underwent high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation and received granulocyte colony-stimulating factor either on posttransplant day 0 (16 patients) or day 8 (16 patients). The day 0 and day 8 groups had no statistically significant differences in age, sex, weight, height, body surface area, disease characteristics, pretransplant harvesting or conditioning regimens, or transplant CD34+ cell counts. Our main outcome measure was the mean time to reach absolute neutrophil count greater than or equal to 0.5 x 10(9)/l, the number of hospital days after transplant, and the total hospital days. The mean days to neutrophil recovery (10.56 versus 9.68, p = 0.48), posttransplant hospital days (13.62 versus 12.81, p = 0.39), and total hospital days (20.25 versus 20.25, p = 1.00) were not significantly different between day 8 and day 0 groups, respectively. No significant effects on neutrophil recovery time, posttransplant hospital days, or total hospital days were observed with the initial granulocyte colony-stimulating factor infusion on day 0 versus day 8 after transplant. Delayed administration may allow substantial cost savings (US$200 x 8 approximately equal to US $1,600 per patient) without affecting clinical outcome. More studies are needed to determine whether greater delay is feasible.

Adult↗

Quality of life and patients with cancer: a comparative study of patient versus physician perceptions and its implications for cancer education.

A group of 300 matched pairs of adult patients with cancer (PWC) and their physicians were interviewed concerning the effects of disease and treatment on the patients' quality of life (QL). Patients were asked to rate specific QL factors that concerned them personally, while physicians were asked to evaluate the QL concerns of a hypothetical patient population exhibiting characteristics and diagnoses similar to those of their matched patients. The results indicated that physicians failed to recognize age as a factor having a direct impact upon the QL of their patients. Specifically, physicians estimated that elderly PWC, rather than young PWC, experienced more problems in four out of five QL categories, while in actuality younger patients reported more difficulties in all five categories when compared to their older counterparts. These data suggest that physicians should become more sensitive to the individualized, personal nature of their patients' QL and the factors that may shape or modify it. Implications for cancer education suggest a focus upon determining specific PWC needs as opposed to teaching general QL problems. Students should also be taught not to assume that all PWC experience the same QL concerns; rather, students should be taught to develop a specific history seeking to determine these needs. Finally, educators and students should recognize that young PWC apparently have more difficulty with their disease and its therapy than older PWC.

Adult↗

RBC improved survival due to recombinant human erythropoietin explains effectiveness of less frequent, low dose subcutaneous therapy.

Effectiveness of less frequent, once weekly, low dose subcutaneous recombinant human erythropoietin (rHuEPO) in maintaining 35% hematocrit in patients with chronic renal failure, predialysis and ESRD receiving dialysis, is dependent on rHuEPO induced prolonged RBC survival. One year of weekly rHuEPO doses to 7 patients originally part of the National Cooperative Protocol were evaluated for a total of 372 weeks for an average of 53 weeks per patient. The original 8 to 12 week dosage was directed by protocol for units per dose at 3 doses per week (4 IV, 3 subcutaneous). Thereafter, all doses were subcutaneous. Units/dose and doses/week were titrated to keep hematocrit at 35-38%. Dosage reduction of rHuEPO was determined by two investigators at the time of each examination. Statistical correlation was performed on effect of rHuEPO on 51Cr T1/2 RBC survival changes and changes of rHuEPO weekly doses. Patients evaluated at specific time points in the study were compared to themselves as their own controls by paired t-test analysis. The long-term increased RBC count correlated with prolonged RBC survival by 51Cr T1/2 rather than reticulocytosis. A relatively increased ease of sustaining the target hematocrit of 35% was demonstrated from the 8th week to 1 year. Thirty-two percent of the expanded RBC mass was older at 12 weeks and 22% was older at 1 year. rHuEPO dosage was reduced to 27% at weeks 8-12, to 21% at weeks 20-24, and to 38% at 1 year corresponding to prolonged RBC survival. 51Cr T1/2 increased from 21.6 days control to 28.6 days at 12 weeks and 26.3 days at 1 year.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

High-dose cytosine arabinoside and etoposide in the treatment of relapsed or refractory adult leukemia.

Thirteen patients with leukemia were treated with a combination of cytosine arabinoside (ara-C) (3 g/m2 by 1-h infusion every 12 h for 12 doses) and etoposide (100 mg/m2 daily over 1 h for 3 doses). Toxicity of the regimen consisted of severe hematologic suppression, moderate abdominal colic with vomiting and diarrhea, and occasionally severe central nervous system (CNS) toxicity. Two patients received the regimen as consolidation for acute myelogenous leukemia in remission. Of the remaining 11 patients with chronic myeloid leukemia (CML)-blast crises or relapsed/refractory acute myeloid leukemia (AML), nine patients (82%) obtained CR (or chronic phase) and two patients obtained partial remission (PR). High-dose ara-C and etoposide is an effective but toxic regiment for the treatment of relapsed or refractory myeloid leukemias.

Adult↗

Cardiovascular hemodynamic effects of correction of anemia of chronic renal failure with recombinant-human erythropoietin.

The results of 8 to 12 weeks of treatment of the anemia of uremia with rHuEPO in patients with chronic renal failure and uremia are: a sustained increased hematocrit; increased RBC mass, and subsequent increased MAP; and increased TPRI. The observed trends of decreased LVEF, and echo Doppler evidence of a trend toward LV systolic and diastolic dysfunction, although not individually statistically significant, represent 3 separate evaluation techniques coupled with hypertension and TPRI increase during administration of rHuEPO to increase the hematocrit and packed red blood cell volume in patients with chronic renal failure and anemia. Increased TPRI and hypertension associated with correction of uremic anemia vasodilation and the increased blood viscosity have been noted in earlier investigations with transfusions. The hypertension and elevated TPRI demonstrated during rHuEPO therapy in patients with progressive chronic renal failure associated with increased hematocrit, and the trends toward systolic and diastolic cardiac dysfunction are noted herein. These changes were associated with the combined increase of packed RBC mass and plasma volume in this study. The natural progressive course of worsening of renal function exhibited by these patients could have limited their ability to regulate plasma volume, making them vulnerable to volume-dependent hypertension and a significant preload adding to potential cardiac dysfunction in addition to the increased TPRI.

Anemia↗

An unusual extramedullary relapse of acute nonlymphocytic leukemia after allogeneic bone marrow transplantation.

Recurrent leukemia following allogeneic bone marrow transplantation (BMT) for acute nonlymphocytic leukemia (ANLL) continues to be a cause of morbidity and mortality. Most relapses occur within the first 6-12 months, although disease-free survival curves do not begin to plateau until 24 months posttransplant. The majority of relapses occur in the bone marrow. Extramedullary relapses usually occur in "sequestered sites," i.e., the testis and central nervous system. Although the true incidence of extramedullary relapse in "nonsequestered" sites after allogeneic BMT for ANLL is unknown, it appears that this type of relapse is distinctly unusual. The authors present a case of an unusual extramedullary relapse of ANLL in the breast at day +613 after allogeneic BMT for ANLL. In addition, we briefly review the English BMT literature and discuss the differential diagnosis of breast masses in women who survive allogeneic BMT for ANLL.

Adult↗

Attenuated high-dose cytosine arabinoside in the treatment of the elderly patient with acute nonlymphocytic leukemia. An Eastern Cooperative Oncology Group Pilot Study.

Seventeen elderly patients with acute nonlymphocytic leukemia (EP-ANLL) were treated with cytarabine, either 1.5 g/m2 or 2.0 g/m2 q 12 h for 4 days [attenuated high-dose ARA-C (HDARAC)]. One complete and one partial response was seen in 15 evaluable cases. Toxicity, evaluated in all 17 patients, was severe, with 47% showing a variety of Eastern Cooperative Oncology Group grade 3, 4, or 5 toxicities. Forty-one percent of all patients died within 33 days of initiating treatment. We conclude that attenuated HDARAC is ineffective in inducing remission and is very toxic in the EP-ANLL.

Aged↗

Unmet needs of persons with cancer in Pennsylvania during the period of terminal care.

A stratified random sample of recent cancer deaths was drawn from the Pennsylvania death registry, and 433 family members or close friends were interviewed concerning unmet needs during the last month of life. It was estimated that 72% of persons who died of cancer in Pennsylvania experienced at least one unmet service need during this period. The most frequently reported was help with activities of daily living, estimated at 42% of cancer deaths, involving over 11,000 persons each year in the state. There were significantly more unmet needs during the terminal period, compared with just after diagnosis, in activities of daily living, obtaining health care, transportation, and problems with medical staff. Our findings indicate a need to increase a broad range of support programs during the terminal period, especially of home-care services.

Activities of Daily Living↗

A comparison of problems reported by persons with cancer and their same sex siblings.

Problem reporting rates of 180 persons with cancer (PWC) were compared with those of their closest in age same sex cancer-free siblings living outside their households for the same time periods. PWC had significantly higher reporting rates for physical, activities of daily living, nutrition, and emotional problems and a significantly lower rate for family problems. Sibling problem reporting rates, which indicate the likelihood that PWC would have experienced similar problems without a diagnosis of cancer, were highest for physical, emotional, employment, and family problems suggesting that noncancer factors are especially likely to play a role in those types of problems. Regression analyses showed that female and younger PWCs tended to report more problems than their siblings suggesting that they were more affected by cancer and its treatments than were other types of PWC.

Activities of Daily Living↗

Amsacrine [4'-(9-acridinylamino)-methanesulfon-m-anisidide] (m-AMSA) and 5-azacytidine (AZA) for remission reinduction in patients with relapsed adult acute nonlymphocytic leukemia. An ECOG pilot study. Eastern Cooperative Oncology Group.

Twenty-two evaluable adult patients with relapsed, acute nonlymphocytic leukemia (ANLL) were treated with the combination of amsacrine (m-AMSA) and 5-azacytidine (AZA) as part of an Eastern Cooperative Oncology Group (ECOG) pilot study to evaluate efficacy and toxicity. Each drug was given in a dosage of 150 mg/m2 i.v. daily for 5 consecutive days. A complete response (CR) was obtained in 8 of 22 patients (36%) and a partial response was seen in two others, yielding an overall response rate of 45%. Median survival for all 22 patients was 2.5 months, but medium survival was 7.2 months (range 4.3-13 months) for those with a CR. Twelve of 22 died during the first 3 months, seven of these during the period of drug-induced aplasia. Moderate to severe toxicity included serious infection (16 of 22); nausea, vomiting, and diarrhea (19 of 22); and mucositis (10 of 22). There were four instances each of cardiac abnormalities and hepatic abnormalities but all reversed spontaneously. We conclude that this combination therapy cannot be recommended for further investigation in relapsed patients with ANLL since there was no notable increase in long-term survival and since there were 10 treatment-related deaths out of 22 patients.

Acute Disease↗

Unmet psychological, social, and economic needs of persons with cancer in Pennsylvania.

Six hundred twenty-nine persons with cancer (PWC) selected from the Pennsylvania Cancer Registry plus 397 nonprofessional (support) persons involved in their care (SP) were interviewed to determine their views of the unmet psychological, social and economic needs of PWC. The most frequently mentioned unmet need was for help in dealing with emotional problems (estimated at 25% of PWC state-wide). Other unmet need estimates ranged from 14% for financial to 4% for transportation, with 59% of PWC reporting at least one unmet need. Characteristics of PWC reporting unmet needs included being younger, a history of emotional problems, a chronic illness in addition to cancer, more advanced stage at diagnosis, and a diagnosis of lung cancer. The percent of PWC and CP reporting unmet needs were very similar. These findings indicate that more effective screening for psychosocial problems and referral to supportive services is needed.

Emotions↗

Full dose versus attenuated dose daunorubicin, cytosine arabinoside, and 6-thioguanine in the treatment of acute nonlymphocytic leukemia in the elderly.

Between July 1, 1981 and November 1, 1982, 45 patients with acute nonlymphocytic leukemia (age, greater than or equal to 70 years) were randomly assigned to receive induction chemotherapy using either daunorubicin, cytosine arabinoside, and 6-thioguanine in full dosage (F DAT) or an attenuated schedule of the same drugs (At DAT) as part of an Eastern Cooperative Oncology Group controlled trial. Forty patients were deemed evaluable, 20 on each arm. The overall complete remission (CR) rate for all patients in both arms was 28% (11/40). There was no significant difference in CR rates between the two arms. There were 12 early deaths (less than 60 days) in the F DAT arm compared with only five early deaths on the At DAT arm (P = .05). Due primarily to this early death rate, the median survival for the F DAT group was 29 days v 159 days for the At DAT groups (P = .02). The range of survival of the patients in CR for the At DAT group given either one or two cycles of induction therapy was 121 to 414 days, while the survival range for the F DAT CR patients was 121-186 + days. The median survival for those not achieving CR was 14 days for the F DAT group v 80 days for the At DAT (P less than .02). Fifty-nine percent of the At DAT patients spent greater than 100 days out of the hospital v 12% for the F DAT group. Attenuated chemotherapy with lower doses of DAT is the preferred induction regimen for elderly patients with acute nonlymphocytic leukemia since it causes fewer early deaths, allows a better quality of life, and yields survival times as durable as intensive therapy.

Acute Disease↗

A randomized study of the efficacy of consolidation therapy in adult acute nonlymphocytic leukemia.

The Eastern Cooperative Oncology Group conducted a randomized study to determine the efficacy of consolidation therapy in prolonging the duration of complete remission (CR) in adults with acute nonlymphocytic leukemia (ANLL). Induction chemotherapy with daunorubicin, cytosine arabinoside, and 6-thioguanine (DAT) yielded CR in 65% of 283 patients with ANLL, aged 16-69. For patients aged 60-69, the CR rate was 58%. Of 184 patients in CR, 146 patients were then randomized to receive either maintenance therapy with weekly cytosine arabinoside and 6-thioguanine alone (69 patients) or two courses of reduced doses of DAT 1 mo apart, before commencing the same maintenance program (77 patients). Consolidation therapy resulted in hematologic toxicity, but was not lethal in any of the eligible patients. Patients receiving consolidation plus maintenance therapy experienced a longer CR duration (40 wk) and disease-free survival at 2 yr (28%) than did those patients receiving maintenance therapy alone (34 wk and 14%, respectively). These differences are not statistically significant. These results suggest that approaches to consolidation therapy employing reduced doses of the induction therapy regimen can have, at best, only a small benefit. For consolidation therapy to provide substantial improvement in CR duration, intensive regimens with non-cross-resistant drugs will be required.

Acute Disease↗

Effects of oxaprozin alone or in combination with aspirin on hemostasis and plasma protein binding.

Oxaprozin, a new nonsteroidal antiinflammatory agent, was studied alone and in combination with aspirin for its effects on hemostasis and protein binding in 10 healthy adults. When both oxaprozin and aspirin were given separately for seven days and in combination for five days, both drugs prolonged bleeding time and inhibited collagen- and epinephrine-induced platelet aggregation to a similar degree. The effects of the combination of oxaprozin and aspirin were not additive. The data from the protein binding study showed that oxaprozin was more than 99 per cent bound to plasma proteins. Aspirin displaced oxaprozin from its binding sites. As a result, the rate of plasma clearance of oxaprozin significantly increased from 20 to 26 ml/min/kg (P less than 0.05), and the plasma half-life decreased from 45 to 40 hours. Platelet count and the humoral clotting mechanism were not affected by either drug alone or in combination. There was no clinical evidence of bleeding. One subject who received oxaprozin for 12 days and, in addition, aspirin for the last five days developed a rash that subsided after both drugs were discontinued; one subject treated with aspirin experienced tinnitus. These data suggest that oxaprozin, like aspirin and other nonsteroidal antiinflammatory drugs, should be used with caution when administered to patients who have suffered trauma, who undergo surgery, or who have known defects in hemostasis.

Adult↗