Biomedical subjects

R Ramlau

Publications and source records attributed to R Ramlau.

13 recordsLinked to original sources

PubMed2006

Docetaxel-based induction therapy prior to radiotherapy with or without docetaxel for non-small-cell lung cancer.

This trial aimed to assess the feasibility and tumour control of concurrent chemoradiotherapy or radiotherapy alone after docetaxel-based induction chemotherapy in locally advanced non-small-cell lung cancer (NSCLC). Patients with stage IIIA/IIIB NSCLC received two 21-day cycles of induction chemotherapy with docetaxel (85 mg m(-2), day 1) plus cisplatin (40 mg m(-2), days 1 and 2). Patients without disease progression on day 43 were randomised to radiotherapy (2 Gy for 5 days week(-1); total 60 Gy) alone or with docetaxel 20 mg m(-2) once weekly every 6 weeks. Of 108 patients who received induction chemotherapy, 104 were evaluable for response. After induction chemotherapy, the overall response rate (ORR) was 44%; 91 (88%) patients had no disease progression and 89 were subsequently randomised to local treatment. After randomised therapy, the ORR was 53% (chemoradiotherapy 58%; radiotherapy 48%). Median survival and time to progression were 14.9 and 7.8 months, respectively, for chemoradiotherapy and 14.0 and 7.5 months, respectively, for radiotherapy. The most common toxicities during induction chemotherapy and randomised therapy were grades 3-4 neutropenia and grade 3 lymphocytopenia, respectively. Docetaxel-cisplatin induction therapy followed by concurrent docetaxel and thoracic radiotherapy is a feasible treatment option, showing good clinical activity and tolerability, for locally advanced NSCLC.

Adolescent↗

PubMed2004

Phase II trial of oral vinorelbine in combination with cisplatin followed by consolidation therapy with oral vinorelbine in advanced NSCLC.

BACKGROUND: Among the cytotoxic agents commonly combined with cisplatin in the treatment of advanced NSCLC, vinorelbine has led to significant outcome improvements. Adding more than four cycles of the combination regimen increase toxicities. The availability of an oral form of vinorelbine appeared as a particularly convenient way to provide a consolidation treatment to patients who have achieved an objective response or stable disease. PATIENTS AND METHODS: This multi-centre phase II open-label, non-comparative study was designed to evaluate the treatment with four cycles of the combination chemotherapy with oral vinorelbine at the dose of 60 mg/m2 on day 1 and day 8 for the first cycle and then 80 mg/m2 plus cisplatin 80 mg/m2 on day 1 every 3 weeks followed for patients with objective response or stable disease by consolidation therapy with oral vinorelbine at 80 mg/m2 weekly on patients with unresectable localised or metastatic non-small-cell lung cancer (NSCLC). The primary endpoint was tumor response. The secondary objectives were progression free-survival, overall survival and toxicity assessment. Visual analogue scales (VAS) filled by the patients were also used to evaluate subjective changes under treatment, reflecting patients' clinical benefit. RESULTS: Fifty-six patients enrolled into the study from April 2001 to April 2002 received the combination regimen. Twenty-five patients (43.9%) also received the subsequent consolidation treatment. Partial tumor responses were obtained in 13 patients (26.5%, 95% CI 15.0-41.1) of 49 evaluable patients. Stable disease was observed in 22 (44.9%) of patients. The median duration of response was 6 months (95% CI 4.3-8.2). The median progression free-survival was 4.2 months (95% CI 2.8-6). The median overall survival time was 10 months (95% CI 7.4-14) and the 1 year survival was 42.6%. The main toxicities recorded were haematological. Grade 3 and 4 neutropenia were observed in 16 patients (29.1%). Nausea, vomiting and fatigue were the major non-haematological toxicities reported. Among the symptoms recorded by the patients on VAS scales (appetite, fatigue, pain, cough, dyspnea, haemoptysis), except anorexia, all symptoms were improved during the combination therapy and in the consolidation phase. CONCLUSION: This study confirms that the efficacy of the cisplatin/oral vinorelbine combination in NSCLC is comparable to cisplatin/I.V. vinorelbine. This study also suggests that consolidation therapy with vinorelbine alone may probably prolong the efficacy of the combination regimen. The convenience offered to patients by an oral form of vinorelbine is a definite asset for consolidation therapy.

Administration, Oral↗

PubMed2004

Extended pneumonectomy for non small cell lung cancer--should we still do it?

The aim of the study was to assess the early and late results of extended pneumonectomies in lung cancer patients with T3 and T4 disease. Between Jan. 1995 and Dec. 1999--445 pneumonectomies were performed in patients with lung cancer. In 37 patients without preoperative N2 involvement a standard pneumonectomy was extended to include the following additional resections: chest wall (10), pericardium (9), diaphragm (5), VCS (3), descending aorta (2), left atrium (5), esophagus (1) and tracheal bifurcation (2). The effect of various factors on general mortality and morbidity was analyzed with the use of binary logistic regression. There were two early postoperative deaths (6.8%). Major complications occurred in 10 patients (29%). Overall survival rates at 1, 2, and 3 years were 43, 30 and 24%, respectively. The survival rates for the subgroup with chest involvement only were 50, 42 and 30%, respectively. Eight patients survived beyond the 36 month follow-up. The only factor significantly affecting mortality was incomplete resection, as revealed by postoperative microscopic examination (R1, p<0.05). Extended operations are justified by a relatively low mortality rate and low number of severe postoperative complications, specially in patients with chest wall involvement only. The result of this treatment predominantly depends upon the completeness of the resection.

Aged↗

PubMed2004

Advanced tracheal carcinoma--a therapeutic significance of HDR brachytherapy in palliative treatment.

The purpose of this study was to determine the benefit of high dose rate endotracheal brachytherapy as an exclusive palliative treatment of obstructive tracheal cancer. Thirty-five patients with advanced tracheal carcinoma were treated between May 1999 and March 2001 in Greatpoland Cancer Center. They were qualified for brachytherapy due to life-threatening situations. Fourteen patients were irradiated using three fractions 7.5 Gy each one every week, six patients received three fractions 10 Gy each one every week and fifteen patients received one fraction of 10 Gy. Survival time was compared with chosen clinical factors (age, sex, Karnofsky status, tumor location, lymph nodes involvement and percent of obturation) and prescribed dose. The median survival (Kaplan-Meier) for all patients was 6.6 months. Patients with an endoscopically controlled complete remission 4 weeks after the treatment had a significantly better survival in comparison to patients with a partial remission or no change of tumor size (p=0.0003). Univariate analysis revealed significant difference between patients with Karnofsky score equal with 60 or lower (28/35, 80%) and higher than 60 (7/35, 20.0%) (p=0.005). Difference between the grade of tumor obturation (more than 60% of tracheal lumen (27/35, 77.1%), 60% or lower (8/35, 22.9%) was found in univariate analysis (p=0.04). In multivariate analysis statistically important prognostic factor for survival was Karnofsky score (p=0.04). Statistical analysis revealed no differences in survival according to sex and age (p=0.43 for age, p=0.19 for sex), tumor localization (p=0.13), lymph node involvement (p=0.48) or fractionation scheme (p=0.62). Exclusive HDR brachytherapy of advanced tracheal carcinoma was a safe palliative method of treatment and caused in many patients prolonged survival and improved quality of life. Most important prognostic factor for survival, confirmed in both univariate and multivariate analysis, was Karnofsky score.

Adult↗

PubMed2003

Oral vinorelbine in combination with cisplatin: a novel active regimen in advanced non-small-cell lung cancer.

BACKGROUND: A phase II trial of alternating i.v. and oral vinorelbine in combination with cisplatin was designed to determine the response rate, safety profile, progression-free survival, overall survival and quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-six chemotherapy-naïve patients received cisplatin 100 mg/m(2) and i.v. vinorelbine 25 mg/m(2) on day 1, followed by oral vinorelbine 60 mg/m(2) on days 8, 15 and 22, every 28 days. RESULTS: After an independent review, the response rate was 33% [95% confidence interval (CI) 20% to 46%]. Median progression-free and overall survival were 5.5 months (95% CI 3.7-6.4) and 8.9 months (95% CI 8.8-11.7), respectively. The most frequent hematological toxicities were neutropenia (grade 3-4 in 73% of patients) and anemia (grade 3-4 in 11% of patients). Grade 3-4 infections and non-hematological toxicities occurred occasionally. QoL for lung cancer related symptoms was stable or improved. CONCLUSIONS: The efficacy and safety of the alternating vinorelbine schedule (i.v. on day 1, oral on days 8, 15 and 22) in combination with cisplatin in advanced NSCLC are similar to those of the standard regimen using exclusively i.v. vinorelbine, whereas ease of administration and patient comfort may favor the novel approach.

Administration, Oral↗

PubMed2003

Serum thrombopoietin levels in patients with reactive thrombocytosis due to lung cancer and in patients with essential thrombocythemia.

In patients with thrombocytosis normal to increased serum thrombopoietin (TPO) levels have been reported. The aim of this study was to investigate the relationship between serum TPO concentration, platelet number and plasma levels of fibrinogen in patients with reactive thrombocytosis (RT) due to lung cancer and in patients with essential (primary) thrombocythemia (ET). A total of 70 newly diagnosed patients with RT or ET (platelet counts >600 G/l) were studied: 45 with RT due to lung cancer (25 with non-small cell lung cancer, NSCLC and 20 with small cell lung cancer, SCLC), and 25 with ET. Twenty normal volunteers were used as controls. TPO was measured by immunoassay technique (ELISA). Mean serum TPO values in patients with RT due to lung cancer were statistically significantly higher than those in patients with ET or in controls. The highest platelet count was seen in patients with ET, and mean plasma fibrinogen levels were the highest in RT patients. In NSCLC patients mean serum TPO concentrations were higher (not statistically significant) than in SCLC, and a statistically significant relationship between TPO serum concentration and fibrinogen level was observed. No correlations between platelet counts and TPO serum concentrations were found. Our results indicate increased serum TPO levels in patients with thrombocytosis in lung cancer which may be related to the activity of neoplasms. In addition, it is postulated that the relatively low TPO values in patients with ET may result from a dysregulation of the feedback loop involved in platelet production.

Adult↗

PubMed2002

ZD0473 treatment in lung cancer: an overview of the clinical trial results.

Three open-label, non-comparative, multicentre Phase II trials have examined the efficacy and tolerability of ZD0473 as first-and second-line therapy in non-small-cell lung cancer (NSCLC) patients and second-line therapy in small-cell lung cancer (SCLC) patients. Patients with second-line NSCLC or SCLC were evaluated as either platinum-sensitive or -resistant, based upon their time to relapse/progression after platinum-based therapy. First-line NSCLC patients (n = 18) received a total of 60 treatment cycles (median number per patient 2.5) whilst second-line NSCLC (n = 50) and SCLC (n = 48) patients both received a total of 127 treatment cycles (median number per patient 2.0). Grade 3/4 anaemia, neutropenia and thrombocytopenia was observed in: 38.8%, 22.2% and 27.7% of first-line NSCLC patients; 12.0%, 24.0% and 50% of second-line NSCLC patients; and 10.4%, 25.0% and 47.9% of second-line SCLC patients, respectively. The most common grade 3/4 non-haematological toxicities in all three trials were lethargy and dyspnoea. No clinically significant oto-, nephro- or neurotoxicity was observed. The first-line treatment of NSCLC produced an overall response rate (OR) of 6.3%. No OR was seen after second-line treatment of NSCLC, while ORs of 15.4% and 8.3% were seen in the platinum-resistant and -sensitive second-line SCLC patients, respectively.

Adult↗

PubMed2001

A multicenter randomized phase II study of oral vs. intravenous vinorelbine in advanced non-small-cell lung cancer patients.

PURPOSE: A randomized phase II trial of oral vs. intravenous (i.v.) vinorelbine was designed to determine the efficacy and safety of oral vinorelbine with an intrapatient dose escalation in previously untreated patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between December 1997 and April 1999, 115 patients with stage IIIB or IV NSCLC were randomized (2 to 1) to receive either oral vinorelbine at a dose of 60 mg/m2/week for the first three administrations and then increased to 80 mg/m2/week in the absence of severe neutropenia, or i.v. vinorelbine at 30 mg/m2/week. RESULTS: One hundred and fourteen patients (76 in the oral arm and 38 in the i.v. arm) were treated. Ninety-eight patients (86%) were eligible and assessable. The two treatment arms were well-balanced for demographic and prognostic features. After external panel review, the response rates in evaluable patients were 14%, in the oral arm and 12% in the i.v. arm. The median progression-free survival with oral and i.v. vinorelbine was 3.2 months and 2.1 months, respectively, and the median survival 9.3 and 7.9 months, respectively. The most common hematological toxicity was neutropenia, which was severe (grade 3-4) in 46% of patients and for 7% of administrations in the oral arm, and in 62% of patients and for 25% of administrations in the i.v. arm. Non-hematological toxicities including nausea, vomiting, anorexia, weight loss, diarrhea .and constipation were generally mild to moderate. CONCLUSION: The activity of oral and i.v. vinorelbine in advanced NSCLC appears to be comparable. The safety profiles of both formulations look qualitatively similar. Oral vinorelbine can therefore be considered a good alternative to i.v. administration.

Administration, Oral↗

PubMed2001

Oral vinorelbine: feasibility and safety profile.

BACKGROUND: Patient preference as well as concerns and difficulties with intravenous access and pharmaco-economic issues have driven the development of oral vinorelbine. PATIENTS AND METHODS: Four phase II studies were conducted in chemotherapy-naive non-small-cell lung cancer (NSCLC) and as first-line chemotherapy of advanced breast cancer (ABC). As recommended in the phase I dose-finding study, the first step used a weekly dose of 80 mg/m2. This regimen was associated with an excessive rate of early deaths (10%) due to complicated neutropenia and led to discontinuation of the first two studies. In a second step, the dose of 60 mg/m2/week was given for the first three courses and subsequently increased to 80 mg/m2/week, in the absence of severe neutropenia. RESULTS: One hundred and thirty eight patients (76 with NSCLC and 62 with ABC) received this regimen, of whom only five were unable to undergo dose escalation. The incidence of febrile neutropenia and neutropenic sepsis were low (2.9 and 3.6%, respectively). Although severe events were uncommon, nausea/vomiting and diarrhoea were frequent and primary prophylaxis with antiemetics should be recommended. CONCLUSIONS: Overall, the safety profile of oral vinorelbine at 60 mg/m2/week for the first three courses with escalation to 80 mg/m2 is qualitatively comparable to that of i.v. vinorelbine at standard doses. Similarly to i.v. chemotherapy, close haematological monitoring is necessary.

Administration, Oral↗

PubMed2000

The prognostic value of DNA content analysis in patients with squamous cell lung cancer treated surgically.

The aims of the study were to assess the degree of ploidy and determine whether it had any influence on the remission time and survival of surgically treated patients with squamous cell lung cancer. The results were then related to the clinical staging, grading, size and location of the tumor. Tissue samples of squamous cell lung carcinoma (n=80) resected between 1995 and 1996 in the Department of Thoracic Surgery at University of Medical Sciences in Poznan were prepared using the modified Hedley's method. The measurements were made by means of a Cytoron Absolute flow cytometer. Abnormal (aneuploid) DNA was found in 45% of the tumors. In the 2-year observation period significantly more patients with aneuploid tumors died (75%) than those with diploid tumors (43.2%), P<0.05. No significant correlation was found between the ploidy and frequency of metastasis to regional lymph nodes, tumor size, location or grading. Estimation of the DNA content in cancer cells appears to be a significant prognostic factor. Furthermore measurement of the DNA content can be useful after surgery to estimate the risk of recurrence.

Adult↗

PubMed2000

Structures of nanometre-size crystals determined from selected-area electron diffraction data.

The structure of a new modification of Ti2Se, the beta-phase, and several related inorganic crystal structures containing elements with atomic numbers between 16 and 40 have been solved by quasi-automatic direct methods from single-crystal electron diffraction patterns of nanometre-size crystals, using the kinematical approximation. The crystals were several thousand times smaller than the minimum size required for single-crystal X-ray diffraction. Atomic coordinates were found with an average accuracy of 0.2 A or better. Experimental data were obtained by standardized techniques for recording and quantifying electron diffraction patterns. The SIR97 program for solving crystal structures from three-dimensional X-ray diffraction data by direct methods was modified to work also with two-dimensional electron diffraction data.

Journal Article↗

PubMed2000

Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.

PURPOSE: To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m(2) (49 patients) or 75 mg/m(2) (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks. RESULTS: One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7. 1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P <.001), as was median survival (7.0 v 4.6 months; log-rank test, P =.047). The difference was more significant for docetaxel 75 mg/m(2) patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P =.010; 1-year survival, 37% v 11%; chi(2) test, P =.003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2), three of whom died, and in one patient treated with docetaxel 75 mg/m(2). Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. CONCLUSION: Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m(2), the benefits of docetaxel therapy outweigh the risks.

Adult↗

PubMed1993

A feasibility study on weight reduction in obese postmenopausal breast cancer patients.

An attempt was made to undertake a randomized clinical trial of weight reduction in obese postmenopausal breast cancer patients as an adjuvant to primary surgical and radiotherapeutic treatment. The rationale was to improve prognosis which has been shown to be worse in the obese (probably because of its effect on extra-ovarian oestrogen production). Difficulties in recruiting a sufficient number of patients and the introduction of tamoxifen as anti-oestrogenic adjuvant therapy led to the decision to modify the aim of the study by limiting it to a feasibility study in 102 patients. In three hospitals in The Netherlands and in two hospitals in Poznan, Poland these patients were randomized in intervention and control groups according to a 3:2 ratio. Weight reduction in the intervention group was achieved by dietary means, ie caloric restriction was adapted to personal needs and behaviour of the patients. After 1 year a median weight loss of 6 kg was reached in both countries. In the Netherlands further follow-up indicated that this result could be maintained for another 2 years.

Aged↗