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Biomedical subjects

J Weick

Publications and source records attributed to J Weick.

11 recordsLinked to original sources
PubMed2005

A randomized, multicenter study of subcutaneous and intravenous darbepoetin alfa for the treatment of chemotherapy-induced anemia.

BACKGROUND: This randomized, open-label study evaluated the efficacy, safety and pharmacokinetics of darbepoetin alfa administered intravenously (i.v.) or subcutaneously (s.c.) in chemotherapy-induced anemia. PATIENTS AND METHODS: Patients received darbepoetin alfa i.v. (n=59) or s.c. (n=59) at a dose of 4.5 mug/kg once weekly for 6 weeks (correction phase) followed by 4.5 mug/kg once every 3 weeks for the remainder of the 18-week treatment period (maintenance phase). RESULTS: During the correction phase, the mean [95% confidence interval (CI)] change in hemoglobin (intention-to-treat) was 1.1 (0.6-1.5) g/dl in the i.v. group and 1.3 (0.9-1.7) g/dl in the s.c. group; using available data, the mean change was 1.4 (1-1.9) g/dl and 1.6 (1.2-2) g/dl, respectively. The percentage (95% CI) of patients maintaining hemoglobin (i.e. average decrease < or =0.5 g/dl) during the maintenance phase was similar between the i.v. (82%; 95% CI 66% to 92%) and s.c. (80%; 95% CI 66% to 90%) groups. Thirty-five per cent (95% CI 20% to 50%) of patients in the i.v. group and 32% of patients in the s.c. group (95% CI 18% to 45%) received red blood cell transfusions during week 5 to the end of the treatment period. Darbepoetin alfa was well tolerated in both groups. No significant difference (P=0.36) in weekly darbepoetin alfa serum concentrations was observed between groups. CONCLUSIONS: Darbepoetin alfa can be administered i.v. or s.c. at equal doses for the treatment of anemia in this setting.

Aged↗
PubMed2002

Assessment of psychological distress in prospective bone marrow transplant patients.

Patient psychological distress is associated with many aspects of the bone marrow transplantation (BMT) process and has been linked with poor treatment outcomes. We assessed psychological distress in potential BMT candidates, and compared patient and nurse coordinator ratings of emotional distress at the time of initial BMT consultation. Fifty patients self-reported psychological distress using both the NCCN Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). Coordinators rated patient emotional distress using the DT and Coordinator Rating Scales that measure anxiety and depression. Fifty and 51% of patients self-reported clinically significant levels of emotional distress and anxiety, respectively, but only 20% self-reported clinically significant levels of depression. There was good correlation between ratings using the brief DT and the more comprehensive HADS. There was significant but only moderate agreement between patient and coordinator ratings of emotional distress and anxiety, with coordinators underestimating the number of patients with high levels of emotional distress. In addition, coordinator ratings of patient emotional distress primarily reflected anxiety, whereas anxiety and depression together only minimally accounted for patient self-reports of psychological distress. These findings suggest that: (1) the DT can be a useful screening device; (2) approximately half of patients at the time of initial consultation for BMT already experience significant levels of psychological distress; and (3) coordinators observe emotional distress primarily as anxiety, but patients experience psychological distress as something more than anxiety and depression.

Adult↗
PubMed1999

Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study.

Therapeutic resistance is a major obstacle in the treatment of acute myeloid leukemia (AML). Such resistance has been associated with rapid drug efflux mediated by the multidrug resistance gene 1 (MDR1; encoding P-glycoprotein) and more recently with expression of other novel proteins conferring multidrug resistance such as MRP1 (multidrug resistance-associated protein 1) and LRP (lung resistance protein). To determine the frequency and clinical significance of MDR1, MRP1, and LRP in younger AML patients, we developed multiparameter flow cytometric assays to quantify expression of these proteins in pretreatment leukemic blasts from 352 newly diagnosed AML patients (median age, 44 years) registered to a single clinical trial (SWOG 8600). Protein expression was further correlated with functional efflux by leukemic blasts [assessed using two substrates: Di(OC)(2) and Rhodamine 123] and with the ability of MDR-reversing agents to inhibit efflux in vitro. MDR1/P-glycoprotein expression, which was highly correlated with cyclosporine-inhibited efflux, was noted in only 35% of these younger AML patients, distinctly lower than the frequency of 71% we previously reported in AML in the elderly (Blood 89:3323, 1997). Interestingly, MDR1 expression and functional drug efflux increased with patient age, from a frequency of only 17% in patients less than 35 years old to 39% in patients aged 50 years (P =.010). In contrast, MRP1 was expressed in only 10% of cases and decreased with patient age (P =. 024). LRP was detected in 43% of cases and increased significantly with increasing white blood cell counts (P =.0015). LRP was also marginally associated with favorable cytogenetics (P =.012) and French-American-British (FAB) AML FAB subtypes (P =.013), being particularly frequent in M4/M5 cases. Only MDR1/P-glycoprotein expression and cyclosporine-inhibited efflux were significantly associated with complete remission (CR) rate (P(MDR1) =.012; P(efflux) =.039) and resistant disease (RD; P(MDR1) =.0007; P(efflux) =.0092). No such correlations were observed for MRP1 (P(CR) =.93; P(RD) =.55) or LRP (P(CR) =.50; P(RD) =.53). None of these parameters were associated with overall or relapse-free survival. Unexpectedly, a distinct and nonoverlapping phenotype was detected in 18% of these cases: cyclosporine-resistant efflux not associated with MDR1, MRP1, or LRP expression, implying the existence of other as yet undefined efflux mechanisms in AML. In summary, MDR1 is less frequent in younger AML patients, which may in part explain their better response to therapy. Neither MRP1 nor LRP are significant predictors of outcome in this patient group. Thus, inclusion of MDR1-modulators alone may benefit younger AML patients with MDR1(+) disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Effect of aggressive daunomycin therapy on survival in acute promyelocytic leukemia.

The Southwest Oncology Group analyzed outcome with cytotoxic chemotherapy for previously untreated acute myeloblastic leukemia (AML) from 1982 through 1986. Results with acute promyelocytic leukemia (APL) prompted comparison with patients from 1986 through 1991 and analysis of factors contributing to APL results. Patient and disease characteristics and treatment outcome were compared for all evaluable patients, with more detailed analysis of factors affecting APL treatment outcome. From 1982 through 1986, median survival and disease-free survival in 45 APL patients were 106 months and greater than 105 months, respectively, versus 6 and 14 months for 417 other AML patients. Such differences were not seen from 1986 through 1991. In the 141 APL patients from 1982 through 1991, after adjusting for significant patient and disease characteristics, higher daunomycin (DNR) doses during induction were significantly associated with higher complete remission rates (P < .0001), longer survival (P < .0001), and longer DFS (P < .0001). Cytosine arabinoside (Ara-C) induction dose, the inclusion of other chemotherapy agents in induction, postremission therapy (consolidation, maintenance, or bone marrow transplantation) other than DNR, APL subtype, and patient age did not appear to significantly affect outcome of APL, except for a significant detrimental effect of high-dose Ara-C in consolidation (P = .0042). Morphologic AML subtypes other than APL did not affect outcome. We conclude that high-dose DNR selectively increases survival in APL. This good survival is important for evaluation of combined all-trans retinoic acid (ATRA)/chemotherapy protocols and for planning future combinations of chemotherapy and ATRA. These results illustrate the need to individualize chemotherapy for subtypes of AML. Therapeutic response of APL is independent of age. Except for APL, morphologic subclassification of AML contributed little prognostic information.

Adolescent↗
PubMed1993

Phase I study of WR-2721 and carboplatin.

Because WR-2721 reduces the toxicity of cisplatin and carboplatin in preclinical systems, we have treated 35 patients in a phase I study of WR-2721 and carboplatin. As the plasma half-life of WR-2721 is short relative to that of carboplatin, WR-2721 was administered in two divided doses. This schedule produced acceptable toxicity in 24 patients treated with carboplatin 400 mg/m2 and escalating doses of WR-2721. In the subsequent 11 patients, WR-2721 was fixed at 740 mg/m2/dose and the dose of carboplatin was escalated. With WR-2721, grade 3-4 thrombopenia (platelets < 50 x 10(9)/l) was produced in 4/5 patients treated with carboplatin 625 mg/m2 and in 1/6 patients treated with carboplatin 500 mg/m2. Carboplatin pharmacokinetic parameters in 4 patients were similar to those reported for carboplatin alone. These results suggest that WR-2721 might increase the maximum tolerated dose of carboplatin from 400 to 500 mg/m2.

Adult↗
PubMed1991

Current dermatologic laser applications in patient care.

Laser is an acronym for Light Amplification by Stimulated Emission of Radiation. Current clinical applications of lasers are changing the practice of dermatology. Research and the changing practice significantly impact dermatologic nursing practice.

Humans↗
PubMed1990

Phase I trial of dipyridamole with 5-fluorouracil and folinic acid.

We have performed two Phase I trials of the combination of dipyridamole, 5-fluorouracil (5-FU), and folinic acid in patients with advanced refractory malignancy, based upon in vitro evidence that dipyridamole can modulate the cytotoxicity of 5-FU. In the first trial, patients were treated every 4 wk with dipyridamole (50 mg/m2) p.o. every 6 h on Days 0 to 6, beginning 24 h prior to the i.v. administration of folinic acid (200 mg/m2) and escalating doses of i.v. 5-FU on Days 1 to 5. The maximum tolerated daily dose of 5-FU that could be given with this combination was 375 mg/m2. Because dipyridamole is extensively bound to plasma proteins, it was hypothesized that the concentrations of free dipyridamole achieved with a dose of 50 mg/m2 were inadequate to modulate the cytotoxicity of 5-FU and folinic acid. Therefore, a second Phase I trial of escalating dose of p.o. dipyridamole was performed. Folinic acid (200 mg/m2) and 5-FU (375 mg/m2) were given i.v. on Days 1 to 5 every 4 wk, beginning 24 h after the start of therapy with dipyridamole; dipyridamole was administered p.o. on Days 0 to 6 at doses of 75, 100, 125, 150, 175, or 200 mg/m2/dose to successive cohorts of patients. Dose-limiting neutropenia, mucositis, and nausea were produced at a dose of 200 mg/m2/dose; the recommended dose of dipyridamole for use in Phase II studies is 175 mg/m2 p.o. every 6 h, or 700 mg/m2/day. At this dose, a mean peak plasma concentration of total dipyridamole of 16.32 mumol and a mean peak plasma concentration of free dipyridamole of 38.30 nmol were observed. Trough concentrations of free dipyridamole averaged 60% of the peak concentrations. Objective antitumor responses were seen in a number of tumor types; five of 13 patients with breast cancer treated with high-dose p.o. dipyridamole, 5-FU, and folinic acid responded. High-dose p.o. dipyridamole can produce plasma concentrations of free dipyridamole within the range shown to modulate the cytotoxicity of 5-FU and other agents. Phase II trials of this combination are justified.

Adult↗
PubMed1990

N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance.

Point mutations of the N-ras proto-oncogenes have been previously detected in 20% to 60% of samples of acute myelogenous leukemia (AML), but the clinical significance of these mutations is presently unclear. We directly sequenced polymerase chain reaction (PCR) amplified N-ras fragments to determine the frequency of N-ras point mutations in 55 adult patients with de novo AML. Mutations were present in 8 of 55 (15%) patients. These mutations were usually in codon 12, 13, or 61, but one patient had mutations in both codons 13 and 61, and another had an unusual point mutation in N-ras codon 60. A comparison of patients with and without N-ras mutations showed no statistically significant differences in pretreatment clinical variables, response to induction therapy, or survival, except for a possibly higher percentage of FAB M4 subtypes in patients with the N-ras mutation. These data together with previous reports suggest that the presence of N-ras point mutations do not clearly define a unique clinical or biologic subset of AML patients.

Adolescent↗
PubMed1978

Unmaintained remissions in multiple myeloma.

Twenty-eight patients with multiple myeloma responding to prior melphalan-prednisone combinations, but without additional chemotherapy, were followed until relapse. Patients receiving no further treatment had a median survival time similar to that of those receiving indefinite courses of melphalan-prednisone or carmustine-prednisone. Prolonged periods of unmaintained remission occurred primarily in patients without extensive disease at the time of diagnosis or in whom the abnormal protein disappeared from the electrophoresis strip. The initial relapse after an unmaintained remission was controlled in 80% of patients with the resumption of melphalan-prednisone, but second remissions were usually less marked in degree and shorter in duration. Results supported the long-term evaluation without chemotherapy of selected patients with low numbers of plasma cells after treatment who were likely to experience long durations of disease stability and respond again to retreatment with melphalan-prednisone.

Cell Transformation, Neoplastic↗
PubMed1977

Combination therapy for multiple myeloma.

The effect of six different chemotherapy regimens were evaluated in 462 previously untreated patients with multiple myeloma. In comparison with other treatments, drug combinations that included vincristine and were given at 3-week intervals were associated with higher response rates and longer survival times. No gain was noted from the use of Adriamycin or from combinations of alkylating agents unless vincristine was given and the treatment intervals were short. Seventy-one responding patients were allocated at random to maintenance treatment with intermittent courses of either azathioprine--prednisone or a combination of melphalan--cyclophosphamide--carmustine (BCNU)--prednisone. The survival time was not prolonged with either maintenance treatment in comparison with that for responding patients continued on other therapies or on no therapy in previous studies. Attempts to reduce tumor was maximally with a change in the therapeutic modality, such as with immunotherapy or radiotherapy, remain to be evaluated.

Antineoplastic Agents↗