Biomedical subjects

G J Locker

Publications and source records attributed to G J Locker.

At least 19 recordsLinked to original sources

PubMed2005

Fulvestrant ('Faslodex') in pre-treated patients with advanced breast cancer: a single-centre experience.

Fulvestrant ('Faslodex') is a new oestrogen receptor (ER) antagonist with no agonist effects. This report describes the experience of a single centre including 126 postmenopausal women with advanced breast cancer (ABC) in a fulvestrant Compassionate Use Programme. All patients had previously received endocrine treatment for early or ABC. Patients received fulvestrant as first- (n=7), second- (n=51), third- (n=50) or fourth-line endocrine therapy (n=18) for ABC (median duration of treatment: 4 months [range 3-27(+) months], follow-up: 13 months [range 1-38(+) months]). Twelve patients had partial responses (PR) and 43 patients experienced stable disease (SD) > or = 6 months (objective response rate: 9.5%; clinical benefit [CB] rate: 43.6%). Ten of 12 patients with a PR had HER2-negative tumours, and 9/12 had ER-positive and progesterone receptor (PgR)-positive disease (two patients had unknown HER2 status and one had unknown ER and PgR status). Nine of the 18 patients with HER2-positive tumours experienced CB with fulvestrant. Although CB rates were similar when fulvestrant was given as first- to fourth-line endocrine treatment, the proportion of those experiencing CB who had a PR appeared to decrease when fulvestrant was used later in the sequence. Fulvestrant was well tolerated; six patients experienced adverse events (all grade I/II). These data demonstrate that fulvestrant is an effective and well-tolerated therapy for patients with ABC progressing on prior therapies.

Adult↗

PubMed2004

Pharmacokinetics of teicoplanin during continuous hemofiltration with a new and a 24-h used highly permeable membrane: rationale for therapeutic drug monitoring-guided dosage.

OBJECTIVE: Continuous venovenous hemofiltration (CVVH) is widely used in the management of critically ill patients, but only few administration guidelines for antimicrobial drugs are available. It is unclear whether the use of a filter for more than 24 hours might lead to less efficient extraction. This study describes the pharmacokinetics of teicoplanin during CVVH using a highly permeable membrane. METHODS: Pharmacokinetics of teicoplanin during continuous hemofiltration with a new (group 1) and a 24-h used (group 2), highly permeable polyamide membrane were assessed in 3 patients. RESULTS: The teicoplanin serum concentrations (44.0 +/- 18.5 mg/l vs 109.5 +/- 34.5 mg/l) and half-life of teicoplanin (4.6 +/- 1.1 h vs 5.2 +/- 0.7 h) differed significantly between the 2 groups indicating a smaller elimination of the drug on the second day. Substantial binding of teicoplanin to filter membranes could explain this observation. CONCLUSION: The results suggest that daily adjustment of the dosage is necessary to achieve sufficient teicoplanin concentrations and a fixed dosage recommendation is not suitable for this drug.

Anti-Bacterial Agents↗

PubMed2002

[Sepsis in hemato-oncologic patients].

The general approach regarding the treatment of sepsis in patients with oncological or haematological malignancies does not differ significantly from that in immunocompetent individuals, however, there are several specialities. The main causes of severe infections in cancer patients include deranged cellular or humoral immunity due to the underlying disease, severe neutropenia as a consequence of cytostatic regimens, lesions of the mucosal barriers due to adverse effects of antineoplastic agents, and violations of the integument by therapeutic interventions. Due to the impaired host defense, life threatening infections can occur more often in these patients, thereby limiting the benefits of antineoplastic therapy. On this account precise and intensive therapy has to be initiated in the early stages of sepsis. In the following, we will not primarily focus on sepsis specific treatment modalities, but merely try to elucidate in more detail the pathomechanisms and special features with regard to infectious complications and specific treatment.

Antineoplastic Agents↗

PubMed2001

Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma.

We performed a pilot-study on pegylated liposomal doxorubicin (PLD) for advanced hepatocellular carcinoma. Seventeen patients received 40 mg/m(2) PLD intravenously every 4 weeks. A clinical benefit response was achieved in 50% (complete remission 7%, minor remission 7%, stable disease 36%). Toxicities were moderate. In view of these encouraging findings, further studies appear warranted.

Adult↗

PubMed2001

Docetaxel monotherapy in heavily pretreated metastatic breast cancer: a multicenter, community-based feasibility trial.

PURPOSE: To evaluate the efficacy and safety of docetaxel in heavily pretreated and anthracycline-resistant patients with metastatic breast cancer in an outpatient setting. PATIENTS AND METHODS: Between February 1996 and June 1998, 98 consecutive patients who had progressed during or relapsed following prior anthracycline-containing chemotherapy were enrolled into the trial. Docetaxel was administered at a dose of 100 mg/m2 by intravenous infusion every 3 weeks. The administration of colony-stimulating factors was at the discretion of the attending physician. Premedication with dexamethasone was mandatory for all patients. RESULTS: Of the 98 patients, 93 were evaluable for toxicity and response. Patients had received two palliative regimens (median, range 1-5) prior to docetaxel treatment. The most frequent toxicity observed was leukopenia grade III and IV (WHO grading system) which occurred in 47% of patients (grade IV only in 14%). Except for alopecia grade III (64% of patients), nonhematologic side effects grade III-IV were rare (1-7% of patients) and included nausea, stomatitis, diarrhea, peripheral neuropathy, fluid retention and pulmonary toxicities. There were no treatment-related deaths. Objective responses occurred in 40% of patients (CR 6%, PR 34%), and stable disease in 38% of patients. The median duration of response was 5.3 months (range 0.7-18.1 months) while the median survival was 15 months (range 2 36 months). CONCLUSION: Docetaxel is a highly active agent in patients with anthracycline-resistant metastatic breast cancer, even in heavily pretreated patients, with moderate toxicity.

Adolescent↗

PubMed2001

Single-dose pharmacokinetics of levofloxacin during continuous veno-venous haemofiltration in critically ill patients.

The present study was performed to analyse the pharmacokinetics of levofloxacin during continuous veno-venous haemofiltration (CVVH) with a high-flux polyamide membrane. Twelve patients received 500 mg levofloxacin intravenously. The mean levofloxacin concentration peak was 1.9 +/- 1.0 mg/L. The elimination half-life, haemofiltration clearance and total removal were 8.3 +/- 2.6 h, 27.6 +/- 8.4 mL/min and 56 +/- 19%, respectively. Further multiple-dose studies are required to enable dosage recommendations to be made for patients receiving renal replacement therapy with CVVH.

Anti-Infective Agents↗

PubMed2001

Unexpected severe myelotoxicity of gemcitabine in pretreated breast cancer patients.

Gemcitabine is a chemotherapeutic agent with proven antitumor effects in pancreatic and non-small cell lung cancer; however, studies establishing the definite significance in other solid tumors are still in progress. We herein present three female patients with advanced breast cancer who received gemcitabine as salvage chemotherapy. Gemcitabine at a dose of 1250 mg/m2 was scheduled for days 1, 8 and 15 with a subsequent rest for 1 week. However, within 1 week after the very first administration of gemcitabine myelotoxicity WHO grade IV occurred in all patients, leading to discontinuation of therapy. In two patients this gemcitabine-induced hematotoxicity could be overcome by means of vigorous supportive care, but one patient died after cerebral bleeding due to severe thrombocytopenia. We conclude that gemcitabine in heavily pretreated breast cancer patients should only be used with extreme caution with special focus on platelet counts until solid data from clinical studies for doses and schedules are available.

Adult↗

PubMed2001

Comparison of prone positioning and continuous rotation of patients with adult respiratory distress syndrome: results of a pilot study.

OBJECTIVE: To compare prone positioning and continuous rotational therapy with respect to oxygenation and hemodynamics in patients suffering from adult respiratory distress syndrome (ARDS). DESIGN: Randomized, prospective pilot study. SETTING: Intensive care unit at a university hospital. PATIENTS: Twenty-six mechanically ventilated patients with ARDS from nontraumatic causes. INTERVENTIONS: Twelve patients were turned prone (group 1), 14 patients underwent continuous axial rotation from one lateral position to the other with a maximum angle of 124 degrees in specially designed beds (group 2). All patients had received inhaled nitric oxide (NO) therapy before positioning. MEASUREMENTS AND MAIN RESULTS: Gas exchange and hemodynamics were assessed using a pulmonary artery catheter. In both groups, an improvement in PaO2/RFIO2-ratio and intrapulmonary shunt fraction occurred after initiation of NO as well as during the first 72 hrs of positioning therapy. During the study period, seven patients died in group 1 and nine patients in group 2 (p = NS). Comparing the areas under the curve during the first 72 hrs, no significant differences with respect to PaO2/FIO2-ratio, PaCO2, positive end-expiratory and peak inspiratory pressure levels, intrapulmonary shunt fraction, the alveolar-arterial oxygen difference, and oxygen delivery and consumption, as well as cardiac index, pulmonary and arterial blood pressures, and pulmonary arterial occlusion pressure could be detected between the groups. Prone positioning was tolerated well, continuous rotational therapy had to be modified according to hemodynamic instability in three patients. CONCLUSIONS: In severe lung injury, continuous rotational therapy seems to exert effects comparable to prone positioning and could serve as alternative when prone positioning seems inadvisable.

Adult↗

PubMed2000

Glutathione in the prevention of cisplatin induced toxicities. A prospectively randomized pilot trial in patients with head and neck cancer and non small cell lung cancer.

PURPOSE: Glutathione has been shown to be an effective chemoprotector against cisplatin-induced side effects in patients with ovarian cancer. In view of this fact, we performed a randomized clinical pilot-trial in the management of other solid tumors in order to compare application of Glutathione to intensive hydration in patients undergoing chemotherapy with a regimen including cisplatin. PATIENTS AND METHODS: Twenty patients suffering from advanced non small cell lung cancer (n = 6) or head- and neck cancer (n = 14) were enrolled in the study. All patients received 80 mg/m2 cisplatin along with etoposide or 5-fluorouracil every 4 weeks. Patients randomized to application of Glutathione (n = 11) received 5 g of Glutathione immediately before application of cisplatin followed by 2000 ml of normal saline. Patients in the control group (n = 9) received 2000 ml electrolyte infusion before and 2000 ml of normal saline with forced diuresis after cisplatin. RESULTS: The intensity of hematologic toxicity was significantly less pronounced in patients treated with Glutathione than in the control group (hemoglobin: 10.7 vs 9.5 mg% respectively, p = 0.039; white blood cell count 3.3 vs 2.2 x 103/microliter respectively, p = 0.004; platelets 167 vs 95 x 103/microliter respectively, p = 0.02), whereas in terms of non-hematologic toxicity no difference was observed. Objective remission occurred in 6 out of 11 evaluable patients from the group receiving Glutathione (55%; complete remission: 9%; partial remission: 46%), and in 4 out of 8 evaluable patients from the control group (partial remission: 50%). However, there was no statistical difference in terms of response and overall survival (13.5 months vs. 10.5 months) between the two groups. CONCLUSIONS: Application of Cisplatin and Glutathione seems to be safe and feasible and the antitumoral efficacy of cisplatin is apparently not impaired by the concomitant use of Glutathione in patients with solid tumors.

Adult↗

PubMed2000

Sequential administration of interferon gamma and interleukin-2 in metastatic renal cell carcinoma: results of a phase II trial. Austrian Renal Cell Carcinoma Study Group.

BACKGROUND: Because of the known efficacy of several cytokines in the treatment of advanced renal cell cancer (RCC), we have conducted a phase II trial of the efficacy and toxicity of subcutaneous interferon gamma (IFNgamma) and interleukin-2 (IL-2). METHODS: 63 patients with progressive metastatic RCC were treated with 100 microg recombinant IFNgamma1b administered three times weekly during weeks 1 and 2 and with 4.5 MU recombinant IL-2 administered on 4 consecutive days during weeks 3 and 4, every 6 weeks. RESULTS: 11% of patients had an objective response (CR: 3%, PR: 8%), 33% had SD. Toxicity was generally mild. The median duration of remissions (CR + PR) was 9.6 months; the median duration of SD 8 months. A significant survival benefit was evident at a median observation time of 51 months for patients (44%) responding to therapy (P < 0.0001). CONCLUSIONS: we conclude that sequential treatment with IFNgamma and IL-2 may prolong survival in patients with metastatic RCC responding to therapy.

Adult↗

PubMed2000

Prostaglandin E(1) does not influence plasmatic coagulation, hepatic synthesis, or postoperative blood loss in patients after coronary-artery bypass grafting.

STUDY OBJECTIVE: To assess whether postoperatively administered prostaglandin E1 (PGE1) might prevent bleeding in patients after coronary artery bypass grafting (CABG). DESIGN: Prospective, randomized, placebo-controlled trial. SETTING: University-affiliated hospital. PATIENTS: 49 patients scheduled for elective CABG surgery. INTERVENTIONS: The PGE1 group received intravenous PGE(1) up to 15 ng/kg/min for 72 hours after surgery, whereas the placebo group received isotonic saline for the same time period. MEASUREMENTS AND MAIN RESULTS: Nine patients (4 in the PGE1 group vs. 5 in the placebo group) had to be excluded because of hemodynamic instability, and 1 in the placebo group because of gastric bleeding. In the remaining 39 patients (20 vs. 19), no significant differences with regard to hemoglobin levels or platelet count could be observed. There was no significant difference between the groups concerning the amount of packed red blood cells, platelet concentrates, or fresh frozen plasma transfused. No significant differences could be observed regarding laboratory markers of coagulation activation or hepatic synthesis either. CONCLUSIONS: PGE1 did not prevent coagulation disturbances and blood loss when administered postoperatively in patients undergoing CABG. The absence of these expected effects might be explained by the concomitant administration of acetylsalicylic acid, whose antiaggregatory acivity seems to exceed the effects of PGE1.

Aged↗

PubMed2000

Vinorelbine and interferon-alpha2c as second-line therapy in metastatic renal cell carcinoma.

Second-line treatment of patients with metastatic renal cell carcinoma (MRCC) progressing under therapy with biological response modifiers (BRM) is an unresolved issue. Thirty-seven patients with MRCC progressing under treatment with BRM received vinorelbine i.v. at a dose of 30 mg/m2 q 22 days and 4,800,000 IU interferon (IFN)-alpha2c s.c. thrice weekly. Partial remission (PR) occurred in 8% of patients, stable disease (SD) (median duration 8, range 3-35+ months) was observed in 46% of patients. Median overall survival was 15 (range 1-49) months. No major toxicities occurred. Patients with MRCC who failed first-line treatment with BRM had a high chance to enter PR or SD under combined, low-toxic therapy with vinorelbine and IFN-alpha2c.

Adult↗

PubMed2000

Outcome and prognostic factors in critically ill cancer patients admitted to the intensive care unit.

OBJECTIVE: To assess survival in cancer patients admitted to an intensive care unit (ICU) with respect to the nature of malignancy, cause of ICU admittance, and course during ICU stay as well as to evaluate the prognostic value of the Acute Physiology and Chronic Health Evaluation (APACHE) III score. DESIGN: Retrospective cohort study. SETTING: ICU at a university cancer referral center. PATIENTS: A total of 414 cancer patients admitted to the ICU during a period of 66 months. INTERVENTIONS: None. MEASUREMENTS: Charts of the patients were analyzed with respect to underlying disease, cause of admission, APACHE III score, need and duration of mechanical ventilation, neutropenia and development of septic shock, as well as ICU survival and survival after discharge. Mortality data were compared with two control groups: 1362 patients admitted to our ICU suffering from diseases other than cancer and 2,776 cancer patients not admitted to the ICU. MAIN RESULTS: ICU survival was 53%, and 1-yr survival was 23%. The 1-yr mortality rate was significantly lower in both control groups. Patients admitted after bone marrow transplantation had the highest mortality. In a multivariate analysis, prognosis was negatively influenced by respiratory insufficiency, the need of mechanical ventilation, and development of septic shock during the ICU stay. Admission after cardiopulmonary resuscitation yielded high ICU mortality but a relatively good long-term prognosis. Admission after surgery and as a result of acute hemorrhage was associated with a good prognosis. Age, neutropenia, and underlying disease did not influence outcome significantly. Admission APACHE III scores were significantly higher in nonsurvivors but failed to predict individual outcome satisfactorily. All patients with APACHE III scores of >80 died at the ICU. CONCLUSION: A combination of factors must be taken into account to estimate a critically ill cancer patient's prognosis in the ICU. The APACHE III scoring system alone should not be used to make decisions about therapy prolongation. Admission to the ICU worsens the prognosis of a cancer patient substantially; however, as ICU mortality is 47%, comparable with severely ill noncancer patients, general reluctance to admit cancer patients to an ICU does not seem to be justified.

APACHE↗

PubMed2000

Benefit of interferon-alpha2b in a patient with unresectable hepatoma and chronic infection with hepatitis C virus.

Only in a small proportion of patients is advanced hepatocellular carcinoma (HCC) resectable, so the need for effective non-surgical treatments is obvious. We present details of a 72-year-old woman with inoperable HCC and chronic infection with hepatitis C virus, proved by the presence of antibodies directed against hepatitis C virus and positive polymerase chain reaction. The patient was treated with subcutaneous recombinant human interferon-alpha-2b. Within a few weeks, a partial tumour remission, paralleled by a decrease in serum levels of tumour markers and liver enzymes, was observed. In addition, polymerase chain reaction became negative. This observation facilitates the hypothesis that the anti-viral effects of interferon might have been jointly responsible for the anti-tumour activity observed. Interferon-alpha might serve as a treatment option in patients with unresectable hepatoma and chronic active viral hepatitis, but prospective studies are warranted.

Aged↗

PubMed2000

Homocysteine and laminin are not prognostic markers in patients with septic inflammatory response syndrome.

The aim of this study was to measure plasma homocysteine and laminin concentrations in patients with nonbacteremic systemic inflammatory response syndrome (SIRS) and to compare them with those of a healthy control group. Concerning laminin, significant increased concentrations could be observed in the SIRS group compared to the control group, but for homocysteine, no significance could be observed. In summary, homocysteine and laminin levels are not useful in the prediction of a patient's outcome.

Adult↗

PubMed2000

Decrease of circulating hematopoietic progenitor cells During interleukin-2 treatment is associated with an increase of vascular cell adhesion molecule-1, a critical molecule for progenitor cell adhesion.

Administration of interleukin-2 (IL-2) to cancer patients has been shown to transiently decrease the number of circulating hematopoietic progenitor cells, but the mechanism of this phenomenon is unknown. Recently, the interaction of vascular adhesion molecule-1 (VCAM-1) with leukocyte very late antigen-4 (VLA-4) has been demonstrated to play a crucial role in the adhesion of progenitor cells to bone marrow stromal elements. Cytokine induced upregulation of VCAM-1 leads to increased binding of progenitor cells to stromal cells in vitro, and inhibition of this interaction by monoclonal antibodies is associated with marked progenitor cell mobilisation in vivo. In the present study we serially determined peripheral blood progenitor cell numbers during IL-2 treatment (10 courses) in 6 cancer patients and determined in parallel levels of soluble VCAM-1 as a surrogate marker for the in vivo activation of this molecule. Our data indicate that continuous intravenous administration of IL-2 for 5 days leads to a marked decrease of circulating progenitor cells associated with a substantial increase of circulating VCAM-1. Circulating myeloid progenitor cells (CFU-GM) dropped from a mean value of 167 +/- 187 / ml pre IL-2 to 16 +/- 15 / ml on day 3 (p < 0.01). Similarily, mean erythroid progenitors (BFU-E) decreased from 282 +/- 204 / ml before IL-2 administration to 86 +/- 61 / ml on day 3 (p < 0.005). In contrast, soluble VCAM-1 rose from a mean value of 1814 +/- 451 ng/ml before to 4607 +/- 736 ng/ml at the end of IL-2 therapy (p < 0.0001). Sera from IL-2 treated patients did not inhibit hematopoietic colony formation from normal bone marrow. These results suggest redistribution and increased adhesion of progenitor cells to stromal and/or endothelial elements during IL-2 via the VCAM-1/VLA-4 interaction as a possible mechanism for the decrease of circulating progenitor cells during IL-2 therapy.

Adult↗

PubMed2000

Relation of pro- and anti-inflammatory cytokines and the production of nitric oxide in patients receiving high-dose immunotherapy with interleukin-2.

Immunotherapy with intravenous recombinant human interleukin-2 (rh IL-2) may be accompanied by hypotension and the emergence of capillary leak syndrome. Nitric oxide (NO) is supposed to be responsible for both side effects. The aim of the current investigation was to elucidate the relationship between pro- and anti-inflammatory cytokines and the production of NO in eight tumor patients receiving intravenous rh IL-2 continuously over a time period of 120 hours. Markers of systemic inflammation, as well as nitrate plasma levels, were consecutively determined. Significant changes in the levels of pro-inflammatory cytokines IL-6 and IL-8 were observed (p < 0.05). In contrast to the anti-inflammatory cytokine IL-10, which did not increase significantly, the serum concentrations of the soluble tumor necrosis factor receptors (sTNFr) I and II rose continuously and significantly during the observation period (p < 0.05). In parallel, a significant rise in nitrate plasma levels was observed (p < 0.05). Moreover, there were highly significant correlations between nitrate and IL-6 serum levels (p < 0.05), nitrate and sTNFr-I (p < 0.05), nitrate and sTNFr-II (p < 0.05), and between IL-6 and IL-10 (p < 0.05), respectively. We conclude that immunotherapy with IL-2 promotes a pro-inflammatory state, parallelled by an increased production of nitric oxide. Although anti-inflammatory responses accompany this process, they are not able to diminish the production of nitric oxide.

Adult↗

PubMed1999

[Clinical phase II-evaluation of neoadjuvant, cytostatic combination chemotherapy with docetaxel and epidoxorubicin in female breast cancer patients (T1-4, N0-2, M0)].

BACKGROUND: Preoperative (neo-adjuvant) chemotherapy is very effective in downstaging primary tumors and moreover is able to prevent advancing metastatic growth early in the course of the disease. METHODS: We report on 38 patients with a median age of 54 years (range, 33-70 years) suffering from biopsy-proven breast cancer (T1-T4). Mastectomy had been considered the treatment of choice in all cases. The patients received 194 cycles of chemotherapy with docetaxel (75 mg/m2) and epidoxorubicin (75 mg/m2) on day 1, every 21 days, together with 30 million IU of G-CSF from days 3 to 10. Three to 8 cycles (median 5 cycles) of the treatment were administered until best response was achieved on mammography and clinical assessment. RESULTS: The neo-adjuvant chemotherapy was well tolerated and all patients completed the treatment regimen on an out-patient basis. During 194 cycles we observed leukopenia WHO grade IV only at one occasion (0.5%). WHO-grade III toxicity consisted of leukopenia (0.5%), diarrhoea (2%), and stomatitis (0.5%). Response to treatment was present in 85%, with 4 patients (11%) experiencing a pathological complete response (pCR) of the invasive tumor (T0: n = 2, DCIS: n = 2) and 28 patients (74%) showing a partial pathological response. In 21 patients (52%) a breast-conserving surgical procedure was possible. SUMMARY: We conclude that neo-adjuvant treatment of primary breast cancer with docetaxel and epidoxorubicin is safe and effective. By applying more chemotherapy cycles preoperatively it might even be possible to raise the rate of pCR and prolong survival.

Adult↗