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Biomedical subjects

R B Weiss

Publications and source records attributed to R B Weiss.

At least 37 records · Page 2Linked to original sources
PubMed1998

A Southwest Oncology Group and Cancer and Leukemia Group B phase II study of doxorubicin, dacarbazine, ifosfamide, and mesna in adults with advanced osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma.

BACKGROUND: Ewing's sarcomas, osteosarcomas, and rhabdomyosarcomas are significantly more responsive to chemotherapy than other sarcomas. Adjuvant chemotherapy is used routinely based on data from randomized trials. Although a percentage of children with locally advanced or metastatic tumors remain curable, few data exist regarding the tumor's natural history or response and survival in adults. METHODS: This Phase II study evaluated doxorubicin, dacarbazine, ifosfamide, and mesna (MAID) in adults with inoperable or metastatic Ewing's sarcoma, rhabdomyosarcoma, or osteosarcoma. RESULTS: Between 1987-1991, 81 patients were entered; 69 patients were eligible. One patient died of neutropenic infection. Ten patients (14%) responded completely and 34 patients (49%) had a complete or partial response. Response rates were significantly higher for patients with Ewing's sarcoma and rhabdomyosarcoma than for those with osteosarcoma (77%, 64%, and 26%, respectively; P < 0.005). Although there were no significant differences in progression free survival by histology, survival for patients with Ewing's sarcoma was significantly longer than for patients with osteosarcoma (P = 0.004.) At the time of last follow-up, 7 patients (10%) were alive without progression: 3 with Ewing's sarcoma, 1 with osteosarcoma, and 3 with rhabdomyosarcoma. CONCLUSIONS: MAID chemotherapy is an active regimen in adults with advanced or metastatic Ewing's sarcoma and rhabdomyosarcoma. Although there was no direct comparison with a doxorubicin and cisplatin-based regimen, the response rate and survival in patients with osteosarcoma suggest that doxorubicin and cisplatin-based chemotherapy would remain the accepted initial chemotherapy regimen. For patients with rhabdomyosarcoma and Ewing's sarcoma, 10-20% of patients remained disease free at 5 years.

Adolescent↗
PubMed1998

Systems of protocol review, quality assurance, and data audit.

The US National Cancer Institute (NCI) is the world's largest sponsor of clinical trials in cancer treatment and biology, and it is responsible for the reliability of data generated by means of its funding. The cooperative groups supported by the NCI consist of main academic institutions and smaller affiliates of these institutions. The size of these groups, their geographical dispersion, and the number of studies accruing patients at any one time make it a challenge to ensure that all requirements of institutional oversight, patient consent, protocol compliance, and data submission and quality are met. Each cooperative group has established various procedures for quality assurance. These include data coordinators at the data management center of the group, study chairs, and statisticians. In addition, each group has a committee of physician-investigators and clinical research associates who make periodic site visits to all member institutions to audit the on-site medical records of a sample of patients entered at that institution. The study records are compared with the medical records for all aspects of protocol management and data generation. In addition, adherence to requirements for consent-form signing and oversight by an institutional review board is assessed. Deviations from the study requirements are evaluated as being minor or major. A written report of the audit result is provided to both the NCI and the relevant administrative components of the cooperative group. The audit process has uncovered rare instances of scientific improprieties in these NCI-funded clinical trials, but more importantly it has educated investigators and support staff to improve adherence to research and data-collection requirements, which has resulted in greater reliability of study results.

Data Collection↗
PubMed1998

Comparison of psychosocial adaptation of advanced stage Hodgkin's disease and acute leukemia survivors. Cancer and Leukemia Group B.

BACKGROUND: The purpose of this study was to compare the long-term psychosocial adaptation of Hodgkin's disease and adult acute leukemia survivors. PATIENTS AND METHODS: Two hundred seventy-three Hodgkin's disease (HD) and 206 adult acute leukemia (AL) survivors were interviewed by telephone concerning their psychosocial adjustment and problems they attributed to having been treated for cancer, using identical research procedures and a common set of instruments. The following measures were used: Psychosocial Adjustment to Illness Scale (PAIS); Brief Symptom Inventory (BSI); current Conditioned Nausea and Vomiting triggered by treatment-related stimuli (CNVI); Indices of Employment, Insurance and Sexual Problems Attributed to Cancer; Negative Socioeconomic Impact of Cancer Index (NSI). All participants had been treated on one of nine Hodgkin's disease or 13 acute leukemia Cancer and Leukemia Group B (CALGB) clinical trials from 1966-1988, and had been off treatment for one year or more (mean years: HD = 5.9; AL = 5.6). RESULTS: HD survivors' risk of having a high distress score on the BSI was almost twice that found for AL survivors (odds ratio = 1.90), with 21% of HD vs. 14% of AL survivors (P < 0.05) having scores that were 1.5 standard deviations above the norm, suggestive of a possible psychiatric disorder. HD survivors reported greater fatigue (POMS Fatigue, P = 0.01; Vigor Subscales, P = 0.001), greater conditioned nausea (CNVI, P < 0.05), greater impact of cancer on their family life (PAIS Domestic Environment, P = 0.004) and poorer sexual functioning (PAIS Sexual Relationships, P = 0.0001), than AL survivors. CONCLUSIONS: Treatment-related issues may have placed HD survivors at a greater risk for problems in long-term adaptation than AL survivors.

Adaptation, Psychological↗
PubMed1998

Heterologous in vitro fertilization and sperm capacitation in an endangered African antelope, the scimitar-horned oryx (Oryx dammah).

Scimitar-horned oryx sperm function was studied using protocols developed for domestic cattle. Objectives were to assess sperm 1) viability and motility in vitro over time, 2) capacitation in heparin- or calcium-supplemented medium, and 3) function in an in vitro fertilization system using heterologous (domestic cow) oocytes. Seminal aliquots were washed, and sperm were resuspended in 1) Talp with 5% fetal calf serum (TALP), 2) TALP + 10 microM heparin, 3) TALP + 20 microM heparin, and 4) TALP + 10 mM CaCl. At 0, 3, and 6 h, aliquots were evaluated for sperm motility, viability (using Hoechst 33258), and ability to acrosome-react when exposed to lysophosphatidylcholine (LC). Sperm function was assessed by evaluating fertilization and embryo development after coculture of in vitro-matured domestic cow oocytes with oryx sperm. Overall mean percentages of motile and viable sperm remained high at 6 h (> 60% and > 70%, respectively). Fewer (p < 0.05) sperm incubated in TALP + 10 microM heparin for 6 h contained intact acrosomes after exposure to LC, but there were no differences between LC and control samples after incubation in TALP without heparin. LC-treated sperm in TALP + 10 mM CaCl contained fewer (p < 0.05) intact acrosomes at 3 and 6 h (52.6% and 31.2%, respectively) than paired controls (83.6% and 70.0%, respectively). Oryx sperm from all males were capable of fertilizing cow oocytes (range 17 of 26 [65.4%] to 25 of 26 [96.2%]). Of the 55 2-cell embryos produced, 34 (61.8%) developed to > or = 8 cells. Of the 24 uncleaved oocytes, 7 (29.2%) were polyspermic. These data demonstrate that processed sperm from the endangered scimitar-horned oryx remain vigorous in vitro for at least 6 h. Capacitation can be induced using cattle sperm-processing techniques, with sperm appearing most responsive to elevated CaCl concentrations. Most interesting was the successful production and development of hybrid embryos after coincubation of oryx sperm with cow oocytes, suggesting that the two bovid species have similar fertilization mechanisms.

Acrosome↗
PubMed1998

Hemolytic anemia after fludarabine therapy for chronic lymphocytic leukemia.

PURPOSE: A report of the clinical features, treatment, and outcome of patients who developed hemolytic anemia (HA) temporally associated with fludarabine (Fludara; Berlex Laboratories, Richmond, CA) therapy for chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Data on 24 patients who developed HA related to fludarabine therapy were collected from the Spontaneous Reporting System of the Food and Drug Administration (FDA) and the Walter Reed Army Medical Center (Washington, DC). RESULTS: Seventeen (71%) patients developed HA after either the first, second, or third cycle of this drug. The longest duration of fludarabine therapy before HA occurred was six cycles. The median decline in hematocrit from baseline during the hemolytic episode was 14.1 (range, 8.0 to 28.9) for the 18 patients for whom this information was available. For the 11 patients for whom transfusion requirements were known, the number of transfusions administered ranged between three and 36. Seven (29%) patients died of medical complications associated with the HA. Seven of eight patients who were re-challenged with fludarabine after an episode of HA developed recurrent HA, and three of these patients died. CONCLUSION: HA associated with fludarabine therapy appears to be uncommon, but it can be severe and fatal, especially if a patient is re-treated with this drug after a previous episode of HA. The mechanism of this toxicity is unknown, but it may be caused by the release of a suppressed auto-antibody to a native red cell antigen.

Adult↗
PubMed1997

Quality of life for adult leukemia survivors treated on clinical trials of Cancer and Leukemia Group B during the period 1971-1988: predictors for later psychologic distress.

BACKGROUND: To identify predictors of psychosocial adjustment for survivors of adult acute leukemia, the adaptation of 206 survivors (77% with acute myelogenous leukemia, and 23% with acute lymphocytic leukemia) treated on any of 13 Cancer and Leukemia Group B trials during the period 1971-1988 was examined. METHODS: Survivors (median age, 41 years) who were at least 1 year from completion of all treatment (median, 5 years) were interviewed by telephone about psychologic symptoms; social, sexual, and vocational function; and beliefs about control over health. Standardized psychologic instruments were used to evaluate survivors' responses. RESULTS: Most survivors adapted well; however, 14% were 1.5 standard deviations above normal on the Global Severity Index of the Brief Symptom Inventory. Predictors of greater psychologic distress included less education, younger age, anticipatory distress during chemotherapy treatment, and the combination of more medical problems after treatment with poorer family function. Anticipatory nausea and distress during chemotherapy predicted persistent visceral distress later, which occurred with reminders of treatment. Anticipatory vomiting predicted a greater tendency toward cancer-related intrusive thoughts and avoidance of reminders. CONCLUSIONS: Patients experiencing anticipatory distress during treatment who are younger and less educated should be monitored for depressive syndromes later.

Adaptation, Psychological↗
PubMed1997

Leukemic thyroiditis as the initial relapsing sign in a patient with acute lymphocytic leukemia and blast expression of the neural cell adhesion molecule.

We report a patient with a history of T-cell ALL in remission who presented with symptoms and laboratory values consistent with subacute thyroiditis but was found to have leukemic thyroiditis as the first clinical manifestation of leukemic relapse. Bone marrow examination at this time demonstrated recurrent ALL. After successful re-induction with chemotherapy and an allogeneic bone marrow transplant this patient developed an isolated recurrence of her ALL manifested by symptomatic thyromegaly and a new mediastinal mass that was treated with irradiation. Despite no medullary recurrence of ALL, the patient developed pleuritic chest pain and shortness of breath and succumbed to pericardial extramedullary leukemia 9 months later. This to our knowledge is the third reported case of symptomatic ALL involvement of the thyroid gland and the first to be confirmed histologically. Furthermore, this patient had blast expression of the neural cell adhesion molecule (CD56), a cell surface marker that has not been studied in ALL but has previously been identified as a risk factor for extramedullary leukemia (EML) in acute non-lymphocytic leukemia. The authors hypothesize that CD56 expression in this patient might have contributed to her predisposition to EML.

Adult↗
PubMed1997

Pharmacokinetics of elemental platinum (ultrafiltrate and total) after a thirty minute intravenous infusion of ormaplatin.

Preclinical data suggest that ormaplatin (tetrachloro-(dl-trans)-1, 2-diamminocyclohexaneplatinum) has substantial activity in cisplatin-resistant tumor models and may be less nephrotoxic than cisplatin. Based on these data we initiated a phase I clinical trial in patients with refractory metastatic cancer. This report characterizes the pharmacokinetic profile of both the total plasma concentrations of elemental platinum and the unbound ultrafiltrate concentrations of elemental platinum, following a 30 min intravenous infusion of ormaplatin. Platinum concentrations were determined by AAS, and pharmacokinetic parameters for both the total plasma concentration and the ultrafiltrate concentration of elemental platinum were determined using both compartmental and noncompartmental methods. Twenty-eight patients (14 males and 14 females; median age, 58) received ormaplatin. There was a linear relationship between Cmax and dose (r2 = 0.945) and AUC and dose (r2 = 0.976). Ormaplatin is more accurately described by a two-compartment model than by a one-compartment model. The distribution half-life (t1/2 alpha) was 0.3 h and the terminal half-life (t1/2 beta) was 39.1 h. The volume of the central compartment (V) was 68.6 L and the volume of distribution at steady state (Vdss) was 183 L. Like total plasma platinum, unbound platinum is also best characterized by a two-compartment model. The elimination of free platinum is also biphasic with a distribution half-life (t1/2 alpha) of 0.3 h and a terminal half-life (t1/2 beta) of 19.3 h. The mean volume of the central compartment (V) was 200.5 L, and the mean volume of distribution at steady state (Vdss) was 560.5 L. Clinical development of ormaplatin has been terminated due to increased frequency of neurological complications noted over other platinum agents; however, the pharmacokinetics are, in general, similar to those of other clinically used platinum compounds.

Adult↗
PubMed1997

Bovine aortic endothelial cells contain an angiotensin-(1-7) receptor.

Angiotensin-(1-7) is a novel peptide of the renin-angiotensin system that counteracts the pressor and proliferative responses to angiotensin II. We now report that cultured bovine aortic endothelial cells contain a saturable, high-affinity [125I]angiotensin-(1-7) binding site with an affinity of 19.3 +/- 10.7 nmol/L and a density of 1351 +/- 710 fmol/mg protein. Angiotensin-(1-7) competed at a second lower-affinity site, with an IC50 of 2.9 mumol/L. The high-affinity angiotensin II receptor antagonist sarcosine1-isoleucine8-angiotensin II blocked [125I]angiotensin-(1-7) binding to bovine aortic endothelial cells at both a high- (IC50 = 1.3 nmol/L) and a low-affinity (IC50 = 6.2 mumol/L) binding site. In contrast, D-alanine7-angiotensin-(1-7) completely blocked [125I]angiotensin-(1-7) binding, with an IC50 of 19.8 nmol/L, suggesting that D-alanine7-angiotensin-(1-7) may selectively block responses to angiotensin-(1-7) in endothelial cells. Neither the AT1 antagonist losartan nor the AT2 antagonist PD 123319 exhibited significant competition for [125I]angiotensin-(1-7) binding to endothelial cells isolated from bovine aorta, in agreement with the absence of detectable mRNAs encoding typical angiotensin receptor subtypes 1 or 2 (AT1 or AT2). Angiotensin II also competed for [125I]angiotensin-(1-7) binding to bovine aortic endothelial cells; however, the relative affinity was 13-fold lower than angiotensin-(1-7), suggesting a preference for angiotensin-(1-7) over angiotensin II. These results demonstrate that bovine aortic endothelial cells contain a unique non-AT1, non-AT2 angiotensin receptor that preferentially binds angiotensin-(1-7).

Angiotensin I↗
PubMed1997

Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461.

PURPOSE: To examine the prognostic significance of extramedullary leukemia (EML) at presentation in patients with t(8;21)(q22;q22) karyotype. PATIENTS AND METHODS: Consecutive patients with t(8;21) treated on Cancer and Leukemia Group B de novo acute myeloid leukemia (AML) treatment studies were examined for the presence of EML (granulocytic sarcoma, subcutaneous nodules, leukemia cutis, or meningeal leukemia) at initial presentation. Clinical features and outcome of t(8;21) patients with and without EML were compared. RESULTS: Of 84 patients with t(8;21), eight (9.5%) had EML manifesting as granulocytic sarcoma (five paraspinal, one breast, and one subcutaneous) or symptomatic meningeal leukemia (n = 1). The pretreatment prognostic variables of t(8;21) patients with and without EML were similar. The hematologic complete remission (CR) rate for t(8;21) patients with EML was 50% versus 92% for those without EML (P=.006). The median CR duration for EML patients was 14.7 months. Patients with EML had a shorter survival (P = 0.002, median 5.4 months versus 59.5 months). This poor outcome may relate to inadequate local (radiation or intrathecal) therapy for patients with spinal or meningeal EML, resulting in residual/recurrent EML following induction chemotherapy (n = 2) or at relapse (n = 1) and permanent neurologic deficits (n = 4). Only one of the EML patients received high-dose cytarabine (HDAC) intensification; this is the only EML patient remaining alive in CR. CONCLUSION: Patients with t(8;21) and EML have a low CR rate and overall survival. An aggressive local and systemic induction therapy should be considered for this patient subset. The effectiveness of HDAC intensification in t(8;21) patients with EML is uncertain and warrants further study.

Adult↗
PubMed1997

Coral reefs, forests, and thermal vents: the worldwide exploration of nature for novel antitumor agents.

Nature has been a source of medicinal treatments for thousands of years, and plant-based systems continue to play an essential role in the primary health care of 80% of the world's population. Nature has provided many of the effective anticancer agents in current use, such as the microbially derived drugs, dactinomycin, bleomycin, and doxorubicin, and the plant-derived drugs vinblastine, irinotecan, topotecan, etoposide, and paclitaxel. The search for novel antitumor agents from natural sources continues with botanists, marine biologists, and microbiologists teaming up with chemists, pharmacologists, toxicologists, and clinicians in the investigation of coral reefs, rainforests, and deep subsurface thermal vents for novel bioactive compounds. The wealth of anticancer drugs of natural origin and critical aspects of the ongoing discovery and development process are discussed.

Animals↗
PubMed1997

A phase I study of topotecan followed sequentially by doxorubicin in patients with advanced malignancies.

Inhibitors of topoisomerase I and topoisomerase II have demonstrated synergy when administered sequentially in several tumor models while having a diminished antitumor effect when given concurrently. To explore the potential for clinical sequence-dependent synergy, we instituted a Phase I study of topotecan (a topoisomerase I inhibitor) followed by doxorubicin (a topoisomerase II inhibitor) in patients with advanced malignancies. Thirty-three patients with advanced malignancies or malignancies for whom no standard therapy exists were entered into the study. Topotecan was administered in escalating doses by 72-h continuous infusion on days 1, 2, and 3, followed by a bolus of doxorubicin given on day 5. To explore the hematological toxicity associated with this sequence, bone marrow aspirates were obtained both prior to the topotecan infusion and immediately prior to the doxorubicin in 10 patients to determine by fluorescence-activated cell sorting analysis whether CD34+ cell synchronization was occurring using this sequential schedule. Dose-limiting hematological toxicity occurred at the first dose-level in three of six patients. Therefore, we defined the maximum-tolerated dose (MTD) below our starting dose-level. Further dose-escalation and a new MTD were defined with the addition of granulocyte-colony stimulating factor (G-CSF). The MTD was, therefore, topotecan 0.35 mg/m2/day continuous i.v. infusion on days 1, 2, and 3, followed by doxorubicin 45 mg/m2 on day 5 without G-CSF, whereas the MTD with G-CSF was topotecan 0.75 mg/m2/day by 72-h continuous i.v. infusion, followed by doxorubicin 45 mg/m2 i.v. bolus on day 5. Ten patients with paired bone marrow aspirates obtained before topotecan and before doxorubicin administrations were available for evaluation. In 7 of 10 patients, there was an increase (16.6 +/- 2.9% to 25.0 +/- 3.5%; P < 0.02) in the proportion of CD34+ cells in S-phase 24 h after the topotecan infusion and prior to doxorubicin compared to the pretreatment values, whereas 1 patient had a decrease in the proportion of CD34+ cells in S phase and 2 patients had no change. Topotecan and doxorubicin with this sequence and schedule can be given safely; the dose-limiting toxicity is hematological toxicity. Alterations in the fraction of hematopoietic progenitor CD34+ cells in S-phase may account for the increased granulocytopenia and thrombocytopenia observed at relatively low dose levels of the combination with and without G-CSF.

Adult↗
PubMed1996

Renal medullary carcinoma: clinical and therapeutic aspects of a newly described tumor.

BACKGROUND: Renal medullary carcinoma is a newly described, aggressive kidney tumor. All patients with the disease have been African-American with sickle cell (SC) trait or hemoglobin SC disease. METHODS: Patient information was obtained from individual patient records and from the Department of Defense national data bank, The Defense Enrollment and Eligibility Reporting System. Data were obtained from either personal review of the patient's records or from discussion with the patient's physician. Cytogenetic studies were performed on one patient. RESULTS: Six patients are presented. All had SC trait. Median age was 24.5 years and 1 patient was female. Time from diagnosis to death averaged 3 months (range 1-7 mos). No objective responses were reported to a wide variety of chemo and immunotherapies: cyclophosphamide, doxorubicin, cisplatin; methotrexate, vinblastine, doxorubicin, and cisplatin; single agent interferon; single agent paclitaxel; or single agent vinblastine. Investigational regimens included topotecan, doxorubicin, and filgrastim; alpha-interferon, interleukin-2, and 5-fluorouracil; and single agent paclitaxel. Cytogenetic studies revealed numerous structural, as well as numerical anomalies. Of the cells successfully karyotyped (n=4), 2 contained abnormalities of chromosome 3 and all contained monosomy 11. CONCLUSIONS: Renal medullary carcinoma is an aggressive, chemoresistant tumor. Time from discovery of tumor to patient death is very short and has been altered by a wide variety of chemotherapies and immunotherapies. An unidentified genetic component is likely present.

Adult↗
PubMed1996

Anaphylactoid reactions to methotrexate.

BACKGROUND: Methotrexate is a chemotherapeutic agent frequently utilized for the treatment of malignant, rheumatic, and pulmonary diseases. Although this agent has been extensively used for more than 45 years, there are few reports of immediate systemic hypersensitivity reactions. The reported immediate reactions include anaphylaxis, urticaria, and hepatitis. However, these reactions have been reported to occur only after some prior exposure to methotrexate. No immediate hypersensitivity reactions to methotrexate have been reported during the initial exposure. We describe two patients who developed immediate systemic hypersensitivity reactions during the initial administration of methotrexate. METHODS: The clinical outcomes of two patients treated by the Hematology/Oncology department at a tertiary care military medical center are described. The National Library of Medicine in Bethesda, Maryland, was electronically searched for the literature review. RESULTS: Patient 1, a 30-year-old male with localized high grade osteosarcoma of the left distal femur, developed generalized pruritus, urticaria, angioedema, and pharyngeal edema within 10 minutes of receiving the initial administration of intravenous high-dose methotrexate. No other pharmaceutical agents, such as antiemetics, were found to cause symptoms on rechallenge. The severity of this reaction precluded continuation of methotrexate therapy. Patient 2, a 23-year-old male with localized high grade osteosarcoma of the right distal tibia, developed pruritus and urticaria within 30 minutes of receiving the initial administration of intravenous high dose methotrexate. This patient, like most patients with immediate hypersensitivity reactions to methotrexate, developed recurrent symptoms during rechallenge of this agent despite prophylactic premedication. CONCLUSIONS: Unlike prior reports in our literature, our cases demonstrate that anaphylactoid reactions can occur during the initial exposure to methotrexate. Clinicians must be prepared to treat potentially life-threatening reactions with both the initial and subsequent doses of methotrexate.

Adult↗
PubMed1996

Immediate hypersensitivity to human recombinant granulocyte-macrophage colony-stimulating factor associated with a positive prick skin test reaction.

BACKGROUND: Recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF), also known as sargramostim, is used to accelerate myeloid recovery following bone marrow transplantation or cytotoxic chemotherapy. "Anaphylactic" reactions to sargramostim have been reported on a limited basis and are poorly characterized. OBJECTIVE: It is the purpose of this report to describe an adverse reaction to sargramostim treatment involving palmar itching, urticaria, angioedema, and throat tightness and to demonstrate the utility of prick skin testing to determine type I sensitization. METHODS: Prick skin testing with 100 and 250 micrograms/mL sargramostim and 300 micrograms/mL rhu G-CSF (filgrastim) was performed in the patient and four control subjects. RESULTS: The patient experienced an immediate wheal and flare reaction with both concentrations of sargramostim while the control subjects demonstrated no reaction. There was also no reaction with filgrastim (rhu G-CSF) in either group and the patient subsequently tolerated filgrastim therapy. CONCLUSION: Prick skin testing with rhu GM-CSF and rhu G-CSF may be useful to demonstrate type I sensitization. Additional studies are needed to determine the incidence and prevalence of skin test reactions in larger numbers of patients with cytokine therapy exposure.

Adult↗