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Biomedical subjects

Robert Pirker

Publications and source records attributed to Robert Pirker.

18 recordsLinked to original sources
PubMed2007

Safety considerations for erythropoietin treatment in patients with cancer.

Cancer-related anaemia, which affects many patients with cancer, can effectively be treated by erythropoietic proteins. Erythropoietic proteins increase haemoglobin levels, reduce the risk for transfusions and also improve the quality of life of patients. When used according to published practice guidelines, these proteins benefit many patients and are generally well tolerated. Important side effects are hypertension and thromboembolic events, either of which occurs in < 10% of the patients. Administration only in anaemic patients, avoidance of target haemoglobin levels > 130 g/l, proper dose adjustments and close monitoring during treatment will ensure the clinical safety of these proteins. However, the association between erythropoietic proteins and outcome of anticancer therapy, including survival, requires further study.

Erythropoietin↗
PubMed2006

Once-weekly epoetin beta (30,000 IU) in anemic patients with lung cancer receiving chemotherapy.

Anemia occurs frequently in patients with lung cancer receiving chemotherapy and has a negative impact on quality of life (QoL). Erythropoietic proteins effectively increase hemoglobin (Hb) levels, reduce transfusion requirements and improve QoL in anemic patients with a range of malignancies. This prospective, observational study evaluated epoetin beta 30,000 IU once weekly in patients with lung cancer in a real-life, clinical-practice setting. Forty patients (72.5% with NSCLC and 27.5% with SCLC) were treated with epoetin beta during any cycle of chemotherapy when Hb decreased to <12 g/dL. Hb levels were assessed at regular intervals and transfusion needs were monitored throughout the study. In total, 72.5% of patients required epoetin treatment by the second cycle of chemotherapy. Epoetin beta treatment duration ranged from 1 to >9 (median 4) weeks. Mean (+/-S.D.) baseline Hb was 10.4+/-1.2 g/dL. Epoetin beta was associated with a rapid increase in Hb levels, with a mean increase of 1.3 g/dL by week 4. Most patients (95%) remained transfusion-free throughout the study. Epoetin beta was well tolerated. This early intervention strategy with epoetin beta 30,000 IU once weekly is an effective and well-tolerated therapy for anemia in patients with lung cancer.

Adult↗
PubMed2006

DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy.

BACKGROUND: Adjuvant cisplatin-based chemotherapy improves survival among patients with completely resected non-small-cell lung cancer, but there is no validated clinical or biologic predictor of the benefit of chemotherapy. METHODS: We used immunohistochemical analysis to determine the expression of the excision repair cross-complementation group 1 (ERCC1) protein in operative specimens of non-small-cell lung cancer. The patients had been enrolled in the International Adjuvant Lung Cancer Trial, thereby allowing a comparison of the effect of adjuvant cisplatin-based chemotherapy on survival, according to ERCC1 expression. Overall survival was analyzed with a Cox model adjusted for clinical and pathological factors. RESULTS: Among 761 tumors, ERCC1 expression was positive in 335 (44%) and negative in 426 (56%). A benefit from cisplatin-based adjuvant chemotherapy was associated with the absence of ERCC1 (test for interaction, P=0.009). Adjuvant chemotherapy, as compared with observation, significantly prolonged survival among patients with ERCC1-negative tumors (adjusted hazard ratio for death, 0.65; 95% confidence interval [CI], 0.50 to 0.86; P=0.002) but not among patients with ERCC1-positive tumors (adjusted hazard ratio for death, 1.14; 95% CI, 0.84 to 1.55; P=0.40). Among patients who did not receive adjuvant chemotherapy, those with ERCC1-positive tumors survived longer than those with ERCC1-negative tumors (adjusted hazard ratio for death, 0.66; 95% CI, 0.49 to 0.90; P=0.009). CONCLUSIONS: Patients with completely resected non-small-cell lung cancer and ERCC1-negative tumors appear to benefit from adjuvant cisplatin-based chemotherapy, whereas patients with ERCC1-positive tumors do not.

Adult↗
PubMed2006

Induction chemotherapy with the TIP regimen (paclitaxel/ifosfamide/cisplatin) in stage III non-small cell lung cancer.

Induction chemotherapy may improve clinical outcome of locally advanced non-small cell lung cancer (NSCLC). To further pursue this, the Austrian Association for the Study of Lung Cancer (AASLC) performed a multi-center phase II trial with TIP induction chemotherapy (Taxol 175 mg/m2 over 3h on day 1, ifosfamide 1000 mg/m2 daily on days 1-3, cisplatin 60 mg/m2 on day 1, and prophylactic filgrastim 5 microg/kg daily on days 4-13). Treatment cycles were repeated every 3 weeks for 3 cycles. Then patients were re-staged and selected for local treatment. Forty-seven patients (33 male, 14 female; median age 58 years, range 36-78; 22 cIIIA, 25 cIIIB; 26 adenocarcinomas, 14 squamous cell carcinomas, 4 large cell carcinomas, 3 undifferentiated carcinomas) were included in this trial. Forty-five patients were evaluable for response and toxicity. An overall response rate of 43% (complete remission 4.5% and partial remission 38%) was achieved. Stable disease and progressive disease were seen in 38 and 15% of the patients, respectively. Down-staging occurred in 36% of the patients. The toxicities of the chemotherapy were mild and, in particular, no severe hematotoxicity was observed. Surgery was performed in 24 (51%) patients and resulted in complete tumor resection in 19 patients. Twenty-four patients received thoracic radiotherapy, 10 patients after surgery. Median survival was 10.3 months for the total population, 13.5 months for patients with cIIIA and 10 months for patients with clinical cIIIB. Survival was longer for patients with down-staging as compared to those without (median not reached versus 10 months, p=0.005) and for patients with complete tumor resection as compared to the remaining patients (27 months versus 10 months, p=0.05). In conclusion, the TIP regimen shows activity and good tolerance as induction chemotherapy in patients with locally advanced NSCLC.

Adult↗
PubMed2005

Clinical role of multidrug resistance protein 1 expression in chemotherapy resistance in early-stage breast cancer: the Austrian Breast and Colorectal Cancer Study Group.

PURPOSE: The multidrug resistance protein 1 (MRP1) is expressed in human breast cancer cells and may contribute to the clinical drug resistance of breast cancer patients. Therefore, we determined the impact of MRP1 expression on the clinical outcome of adjuvant therapy in patients with early-stage breast cancer. PATIENTS AND METHODS: Immunostaining for MRP1 was performed on tissue sections from 516 premenopausal, hormone receptor-positive breast cancer patients with stage I and II disease. Statistical analyses were performed to assess the effect of MRP1 expression on survival and to test for interaction between MRP1 expression and treatment. RESULTS: MRP1 expression independently predicted shorter relapse-free survival (RFS) and overall survival (OS) in patients treated with cyclophosphamide, methotrexate, and fluorouracil (CMF; RFS: hazard ratio [HR] = 1.48; 95% CI, 1.16 to 1.88; P = .002; OS: HR = 1.82; 95% CI, 1.10 to 3.01; P = .02), but it did not predict shorter RFS and OS in patients who received tamoxifen plus goserelin (RFS: HR = 0.99; 95% CI, 0.74 to 1.31; P = .9; OS: HR = 0.68; 95% CI, 0.40 to 1.15; P = .1). Tests for interaction between MRP1 expression and treatment were statistically significant for both RFS (P = .04) and OS (P = .006). CONCLUSION: Our data suggest that MRP1 expression plays an important role in the clinical resistance to adjuvant CMF chemotherapy but does not seem to affect response to adjuvant endocrine treatment with tamoxifen plus goserelin. Thus, MRP1 may be a useful marker for the selection of patients with early-stage breast cancer for the appropriate adjuvant therapy after prospective confirmatory evaluation.

Adult↗
PubMed2005

Randomized phase II evaluation of aprinocarsen in combination with gemcitabine and cisplatin for patients with advanced/metastatic non-small cell lung cancer.

Aprinocarsen is a specific antisense oligonucleotide inhibitor of protein kinase C-alpha. This study aimed to evaluate the response rate to combination therapy with aprinocarsen, gemcitabine and cisplatin, in chemonaive patients with advanced/metastatic NSCLC. Secondary objectives included comparison of response rate, time to event efficacy parameters, and toxicities on the 2 treatment arms. Patients with stage IV, or stage IIIB disease (N3 and/or pleural/pericardial effusion), were randomized to either control or experimental arm. Patients on both arms received gemcitabine 1250 mg/m2 on days 1 and 8, and cisplatin 80 mg/m2 on day 1 of a 3-week cycle. Additionally, on the experimental arm, aprinocarsen was administered as 2 mg/kg continuous iv infusion on days 1-14, every 21 days. A total of 18 enrolled patients were randomized on the 2 arms. Further enrollment was terminated in March 2003 as a result of a phase III trial suggesting that aprinocarsen did not have an added survival benefit when combined with paclitaxel and carboplatin therapy in patients with NSCLC. Patients received a median of 4 cycles on control arm and 2.5 cycles on experimental arm. The response rate was 16.7% in the experimental arm and 44.4% in the control arm. Most frequent grade 3/4 toxicities were hematologic, with a higher incidence of thrombocytopenia in the experimental arm (87.5% vs. 33.3%). Despite the 14-day continuous infusion schedule, infection rate was not increased in the experimental arm. The present study did not show any advantage, in response rate or secondary endpoints, with aprinocarsen; however, the toxicity was not unduly increased, and aprinocarsen regimen was safely administered.

Adult↗
PubMed2004

Highly refractory acute myeloid leukemia.

In this study we evaluated 103 patients suffering from acute myeloid leukemia (AML) who did not respond to induction chemotherapy and defined a sub-group of patients with highly refractory disease characterized by a persistence of more than 1 G/L blast cells in the peripheral blood between days 12 and 16 of the first induction cycle. Only seven patients (one female, six males) met these criteria. Their median age was 65 years (range 41-82 years). Four had de novo AML and three secondary AML. Cytogenetic analysis was performed in six patients: complex aberrations were detected in four patients and, unexpectedly, normal karyotypes were found in the other two. Analysis of multidrug-resistance factors revealed high co-expression of P-glycoprotein (P-gp) and lung resistance protein (LRP) in all four patients with highly refractory disease tested a finding in only 6% of patients with refractory disease and 3% of patients who achieved complete remission (CR) of disease. Furthermore, patients with highly refractory AML had substantially higher leukocyte counts than patients with refractory AML or CR, although this was not significant statistically. Overall, patients with highly refractory AML are characterized by a high incidence of complex cytogenetic aberrations and marked expression of drug transporters.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2004

Therapy of advanced non-small-cell lung cancer (take home message).

Palliative therapy of advanced NSCLC aims at symptom relief, improvement of quality of life and prolongation of survival. This goal is usually achieved by one or more of the following treatment modalities: chemotherapy, radiotherapy, special palliative interventions and general supportive care measures.

Brain Neoplasms↗
PubMed2004

Darbepoetin alfa for the treatment of cancer-related anemia: an update.

Anemia is a common and potentially debilitating complication of cancer. Darbepoetin alfa (Aranesp, Amgen) has been in routine clinical use for the treatment of chemotherapy-induced anemia since 2002. The extended half-life of darbepoetin alfa permits less frequent and consequently more flexible dosing than other erythropoietic therapies. Data suggest that hemoglobin levels can be effectively and safely increased with darbepoetin alfa in cancer patients who are receiving chemotherapy (patients with treatment-induced anemia), and in those who are not receiving chemotherapy (patients with tumor-induced anemia). This review provides an overview of clinical trial results, particularly those exploring flexible, extended dosing schedules.

Anemia↗
PubMed2003

High p27Kip1 expression predicts superior relapse-free and overall survival for premenopausal women with early-stage breast cancer receiving adjuvant treatment with tamoxifen plus goserelin.

PURPOSE: To determine the predictive value of p27Kip1 in premenopausal women with early-stage hormone receptor-positive breast cancer. PATIENTS AND METHODS: We retrospectively examined tumor specimens from 512 patients with breast cancer who were enrolled onto Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 5. In this trial, premenopausal, hormone receptor-positive breast cancer patients with stage I and II disease were randomly assigned to receive either 5 years of tamoxifen plus 3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil. p27Kip1 expression was assessed by immunohistochemistry, and its association with clinical outcome was determined. Statistical analyses were performed to test for interaction between p27Kip1 status and treatment. RESULTS: High p27Kip1 expression (nuclear p27Kip1 staining in >/= 50% of tumor cells) independently predicted superior relapse-free survival (RFS) and overall survival (OS) in both the total study population (RFS: relative risk [RR], 0.53; 95% CI, 0.34 to 0.82; P =.004; OS: RR, 0.29; 95% CI, 0.15 to 0.58; P <.001) and patients treated with combination endocrine therapy (RFS: RR, 0.32; 95% CI, 0.16 to 0.63; P =.001; OS: RR, 0.16; 95% CI, 0.05 to 0.53; P =.003). The interaction between p27Kip1 expression and treatment was statistically significant for RFS (P =.04) but not for OS (P =.27). CONCLUSION: High p27Kip1 expression was an independent predictor of responsiveness to hormonal therapy and thus may be useful for the selection of premenopausal women with early-stage hormone receptor-positive breast cancer for adjuvant combination endocrine therapy.

Adult↗
PubMed2003

Expression of cell cycle regulatory proteins in breast carcinomas before and after preoperative chemotherapy.

Molecular markers predicting response to preoperative chemotherapy would be of major clinical relevance in breast cancer. Therefore, we studied the relationship between the expression of cell cycle regulatory proteins and clinical outcome in breast cancer patients receiving preoperative chemotherapy. Expression of p2lWaf1, p27KiP1, p53, cyclin D3 and Ki-67 was determined in breast carcinomas by means of immunohistochemistry both prior and after preoperative chemotherapy. Expression data were compared with both clinical parameters and response to preoperative chemotherapy with either cyclophosphamide/methotrexate/5-fluorouracil (CMF, n = 29) or epirubicin/docetaxel (ED, n = 36). In paired samples before and after preoperative chemotherapy, the percentage of p21Waf1, p27Kip1, p53 and cyclin D3 positive nuclei of tumor cells in postchemotherapy specimens was significantly higher than the percentage in prechemotherapy samples but no change in Ki-67 expression was observed. High Ki-67 expression (p = 0.02), negative estrogen receptor status (p = 0.01) and negative progesterone receptor status (p = 0.04) were associated with complete pathologic response to chemotherapy, whereas the other markers did not predict response. In conclusion, expression levels of p21Waf1, p27Kip1, p53 and cyclin D3 significantly increased after preoperative chemotherapy in breast carcinomas but only high Ki-67 expression, negative estrogen receptor status and negative progesterone receptor status were associated with complete pathologic response to preoperative chemotherapy.

Adult↗
PubMed2003

Expression of MRP1, LRP and Pgp in breast carcinoma patients treated with preoperative chemotherapy.

Our purpose was to determine the expression of the drug resistance factors multidrug resistance protein (MRP1), lung resistance protein (LRP) and P-glycoprotein (Pgp) in breast carcinoma patients treated with preoperative chemotherapy. We have studied the expression of these proteins in breast carcinomas by immunohistochemistry both prior (n = 80) and after (n = 68) preoperative chemotherapy and compared their expression with response to preoperative chemotherapy. In paired samples prior and after chemotherapy expression of drug resistance factors was significantly lower in prechemotherapy samples as compared with postchemotherapy specimens. This was observed for MRP1 (62% vs. 88%, P < 0.001), LRP (65% vs. 97%, P < 0.001) and Pgp (55% vs. 100%, P < 0.001). Prechemotherapy expression of MRP1 was more frequently observed in patients with distant metastases than in those without (50% vs. 8%, P = 0.02). No associations were observed between LRP expression and clinical parameters. Pgp expression was more frequently detected in lobular carcinomas than in ductal carcinomas (93% vs. 46%, P = 0.001) and in patients with positive lymph nodes than in patients with negative lymph nodes (65% vs. 31%, P = 0.008) but was independent of other clinical parameters. No significant associations were found between the prechemotherapy or postchemotherapy expression of either of these three proteins and response to preoperative chemotherapy. However, prechemotherapy MRP1 expression was significantly associated with shorter progression-free survival of the patients (P = 0.02), whereas no such associations were observed for either LRP or Pgp. In conclusion, preoperative chemotherapy increases the expression of MRP1, LRP and Pgp. Response to chemotherapy is not associated with pre- or postchemotherapy expression levels of these drug resistance proteins but time to progression may be influenced by prechemotherapy MRP1 expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Anemia in lung cancer: clinical impact and management.

Anemia has a high prevalence in patients with lung cancer. Its frequency and severity depend on tumor stage, duration of disease, and previous and current treatment. Anemia affects the health-related quality of life and impacts prognosis and outcome of therapy. Despite this clinical relevance, anemia is often underrecognized and undertreated. Treatment options include the administration of hematopoietic growth factors and red blood cell transfusions. Blood transfusions result in rapid but often transient improvement of anemia. Administration of epoetin or darbepoetin alfa increases hemoglobin levels, decreases blood transfusions, and improves quality of life in patients with lung cancer. Trials determining the exact association of anemia with response to chemotherapy/radiation therapy and survival are ongoing. Oncologists must be aware of the clinical relevance of anemia and offer adequate treatment options to their patients.

Anemia↗
PubMed2002

Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy.

BACKGROUND: Patients receiving chemotherapy often develop anemia. Darbepoetin alfa (Aranesp(TM)) is an erythropoiesis-stimulating glycoprotein that has been shown, in dose-finding studies, to be safe and clinically active when administered to patients with cancer every 1, 2, or 3 weeks. This phase III study compared the safety and efficacy of darbepoetin alfa with placebo in patients with lung cancer receiving chemotherapy. METHODS: In this multicenter, double-blind, placebo-controlled study, 320 anemic patients (hemoglobin or=25% improvement; mean difference = 13%; 95% CI = 2% to 23%, P =.019) than patients receiving placebo. Patients receiving darbepoetin alfa did not appear to have any untoward effect in disease outcome and did not develop antibodies to the drug. Adverse events were similar between the groups. CONCLUSIONS: Patients with chemotherapy-associated anemia can safely and effectively be treated with weekly darbepoetin alfa therapy. Darbepoetin alfa decreased blood transfusion requirements, increased hemoglobin concentration, and decreased fatigue. Although no conclusions can be drawn about survival from this study, the potential salutary effect on disease outcome warrants further investigation in a prospectively designed study.

Adult↗
PubMed2002

Two- versus three-drug combinations in the chemotherapy of advanced non-small-cell lung cancer.

Palliative chemotherapy with three-drug combinations might result in higher efficacy but also enhanced toxicity when compared with two-drug combinations. Italian trials suggested the superiority of cisplatin/gemcitabine/vinorelbine and cisplatin/gemcitabine/paclitaxel over corresponding two-drug combinations. However, a Spanish trial failed to demonstrate an advantage of cisplatin/gemcitabine/vinorelbine over cisplatin/gemcitabine and another multicenter phase III trial did not find differences in response rates and survival between cisplatin/vinorelbine/ifosfamide and cisplatin/vinorelbine. Thus three-drug combinations have not convincingly been demonstrated to be superior to two-drug combinations and should not be considered as standard protocols in advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Darbepoetin alfa: potential role in managing anemia in cancer patients.

Anemia in cancer patients is frequent but often under-recognized and under-treated. This may be related to misconceptions about the impact of anemia on cancer patients and ill-defined guidelines for treatment, as well as the inadequacies of current therapy. Darbepoetin alfa, a novel erythropoiesis-stimulating protein with a longer serum half-life than epoetin (alpha and beta), is approved to treat anemia in patients with chronic kidney disease. Most recently darbepoetin alfa has received approval by the FDA in USA for the treatment of anemia associated with myelosuppressive chemotherapy and approval in the EU is expected soon. Clinical trials in cancer patients indicate that darbepoetin alfa effectively and safely alleviates anemia in patients receiving chemotherapy. A Phase II trial also indicates that darbepoetin alfa is effective in patients who are not receiving chemotherapy. Thus, darbepoetin alfa has the potential to improve supportive care and thereby, cancer patients' quality of life, and might also impact on treatment outcome.

Anemia↗
PubMed2002

Cyclin D3 is a predictive and prognostic factor in diffuse large B-cell lymphoma.

Cyclin D3 is an important regulator for transition from G(1) to the S phase of the cell cycle. Cyclin D3 expression is associated with cell proliferation in lymphoid tissues, but its impact on clinical outcome in non-Hodgkin's lymphomas has not been studied. Therefore, we determined the clinical relevance of cyclin D3 expression in patients with diffuse large B-cell lymphoma. We examined the relation between cyclin D3 expression at diagnosis and response to conventional polychemotherapy and overall survival in 81 previously untreated patients with diffuse large B-cell lymphoma. Cyclin D3 expression was assessed by immunohistochemistry. Cyclin D3 immunostaining ranged from 0-100% (median, 30%) of the lymphoma cells. Patients with high (>or=50% cyclin D3-positive lymphoma cells) cyclin D3 expression had a more advanced clinical stage (P = 0.003) and more often had extranodal disease in more than one site (P = 0.007) than patients with low cyclin D3 expression. Patients with high cyclin D3 expression had a significantly lower complete response rate (17% versus 74%; P < 0.001) and a shorter overall survival (3-year survival rate, 18% versus 74%; P < 0.001) than those with low cyclin D3 expression. Multivariate analyses that included cyclin D3 and the International Prognostic Index demonstrated that cyclin D3 expression had independent effects on the complete response rates and overall survival of the patients. In conclusion, high cyclin D3 expression is an independent predictive and prognostic factor associated with poor clinical outcome in patients with diffuse large B-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗