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Biomedical subjects

C Manegold

Publications and source records attributed to C Manegold.

At least 37 records · Page 2Linked to original sources
PubMed2003

Economic evaluation of antibiotic prophylaxis in small-cell lung cancer patients receiving chemotherapy: an EORTC double-blind placebo-controlled phase III study (08923).

BACKGROUND: To determine whether the cost of prophylactic antibiotics during chemotherapy is offset by cost savings due to a decreased incidence of febrile leukopenia (FL). PATIENTS AND METHODS: Small-cell lung cancer (SCLC) patients were randomised to standard or intensified chemotherapy with granulocyte colony-stimulating factor to assess the impact on survival (n = 244). In addition, patients were randomised to prophylactic ciprofloxacin and roxithromycin or placebo to assess the impact on FL (n = 161). The economic evaluation examined the costs and effects of patients taking antibiotics versus placebo. Medical resource utilisation was documented prospectively, including 33 patients from one centre in The Netherlands (NL) and 49 patients from one centre in Germany (GE). The evaluation takes the perspective of the health insurance systems and of the hospitals. Sensitivity analyses were performed. RESULTS: In the main trial, prophylactic antibiotics reduced the incidence of FL, hospitalisation due to FL and use of therapeutic antibiotics by 50%. In GE, the incidence of FL was not reduced by prophylaxis. This resulted in an average cost difference of only 35 Euros [95% confidence interval (CI) (-)1.713-2.263] in favour of prophylaxis (not significant). In NL, prophylaxis reduced the incidence of FL by nearly 50%, comparable with the results of the main trial, resulting in a cost difference of 2706 Euros [95% CI 810-5948], demonstrating savings in favour of prophylactic antibiotics of nearly 45%. Sensitivity analyses indicate that with an efficacy of prophylaxis of 50%, and with expected costs of antibiotic prophylaxis of 500 Euros or less, cost savings will incur over a broad range of baseline risks for FL; that is, a risk >10-20% for FL per cycle. CONCLUSIONS: Giving oral prophylactic antibiotics to SCLC patients undergoing chemotherapy is the dominant strategy in both GE and NL, demonstrating both cost-savings and superior efficacy. The sensitivity analyses demonstrate that, due to the efficacy of prophylactic antibiotics and their low unit cost, cost savings will incur over a broad range of baseline risks for FL. We recommend the use of prophylactic antibiotics in patients at risk for FL during chemotherapy.

Administration, Oral↗
PubMed2003

ALIMTA (pemetrexed disodium) as second-line treatment of non-small-cell lung cancer: a phase II study.

BACKGROUND: The purpose of this study was to evaluate ALIMTA (pemetrexed disodium, LY231514), a multi-targeted antifolate with first-line activity against non-small-cell lung cancer (NSCLC), in a second-line setting. PATIENTS AND METHODS: Patients with NSCLC were eligible for this phase II study if they had progressive disease within 3 months after first-line chemotherapy or progression while being treated with first-line chemotherapy. In 81 patients studied, two cohorts of patients were assigned based on whether the first-line therapy had included a platinum regimen. ALIMTA was administered at 500 mg/m2 by 10-min intravenous infusion once every 21 days. RESULTS: The response rate in the 79 evaluable patients with poor prognostic features was 8.9% [95% confidence interval (CI) 2.6% to 15.1%]. The response rate in the platinum-pretreated group was 4.5% and 14.1% in the non-platinum-pretreated group. The median duration of response was 6.8 months (95% CI 3.4-7.8 months, 0% censoring). The median survival time was 5.7 months (95% CI 4.0-8.3 months, 7.6% censoring). The probability of survival for at least 6 months was estimated to be 48%. The median time to disease progression was 2 months (95% CI 1.4-2.8 months, 0% censoring). The principal toxicity was myelosuppression, which was reversible. CONCLUSIONS: ALIMTA is active in a second-line setting in non-platinum-pretreated NSCLC patients progressing within 3 months of first-line chemotherapy. This study demonstrates that it is possible to evaluate new drugs against NSCLC in a second-line setting.

Adult↗
PubMed2003

[Docetaxel (Taxotere) as first-line therapy of advanced non-small cell lung cancer (NSCLC)].

Taxotere as a 'stabilizing antitubuline' and a second-generation Taxan has anti-tumor activity in a variety of solid neoplasms. In NSCLC Taxotere has shown encouraging response rates across a range of phase-II studies, and phase-III trials have confirmed its effectiveness in pretreated and chemotherapy-naive patients. Single agent Taxotere has shown that it can significantly improve both survival and quality of life when compared to either best supportive care or standard chemotherapy in previously treated patients. Therefore, it is considered standard for NSCLC second-line chemotherapy. Taxotere has also been evaluated in combination with platinum-compounds and non-platinum-based drugs for first-line treatment of NSCLC. The results recently published from a phase-III registration trial (TAX 326) have shown that the overall survival among patients randomized to receive Taxotere/Cisplatin was better than that among patients treated with Vinorelbin/Cisplatin and similar compared to Vinorelbin/Cisplatin for those patients who received Taxotere/Carboplatin. Given concomitantly or sequentially with non-platinum-based compounds (i.e. Gemcitabine, Vinorelbine) Taxotere has also shown promising activity in randomized studies and may offer advantages for patients not eligible to receive platinum-based compounds.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Calcification in coronary arteries as quantified by CT scans correlated with tobacco consumption in patients with inoperable non-small cell lung cancer treated with three-dimensional radiotherapy.

It has been shown that radiological manifestations of coronary artery sclerosis are an indirect measure of co-morbidity and predictive of survival. The aim of the present study is to evaluate the outcome and side effects after three-dimensional (3D) radiotherapy in patients with unresectable non-small cell lung cancer (NSCLC) stage I, II and IIIA, depending on coronary artery calcification, Karnofsky performance index (KI) and co-morbidity. Between 1993 and 1999, 89 patients with unresectable NSCLC were treated with 3D-radiotherapy. The median age was 66.6 years and median KI 80%. All patients had 3D-treatment planning, based on CT scans. The median total dose was 60 Gy in 2 Gy fractions five times a week. The mean follow-up period was 13.2 months and mean survival time 12.2 months. Significant prognostic factors for improved survival were KI and tumour stage. Patients with a KI<90% had a median survival of 6.5 months compared with 14 months, in patients with KI>/==" BORDER="0">90% (p<0.001). NSCLC stage I+II showed a significantly longer median survival than patients with NSCLC stage IIIA (16.5 months versus 7 months, p<0.004). A significant correlation was seen between pack-years and coronary artery calcification (p<0.05) and between age and marked coronary artery calcification. The incidence of calcification was 67% in smokers (>/==" BORDER="0">20 pack-years) and 43/58 in patients >60 years (p<0.007). Side effects, e.g. pneumonitis, did not correlate with coronary artery calcification but correlated with chronic obstructive lung disease in 19/89 patients. Conventional CT scans for 3D-treatment planning are able to detect coronary artery calcification. There is a significant correlation between age, KI, tobacco consumption and vascular calcification. Although there was a trend to worse overall survival, coronary artery calcification was not a significant predictor of progression-free and overall survival.

Adult↗
PubMed2002

Scorecard endoscopy: a pilot study to assess basic skills in trainees for upper gastrointestinal endoscopy.

BACKGROUND: The development of training models and structured training courses for endoscopic techniques provides practical experience. To assess individual performance and progress in this training we developed and tested a scorecard system. METHODS: Three test groups were compared: group 1, ten physicians without previous endoscopic experience; group 2, ten students, without endoscopic experience; group 3, a control group of experienced endoscopists. Groups 1 and 2 underwent 1 week of training with a theoretical introduction and practical demonstrations. They were assessed by the scorecard daily by an experienced tutor. The individual scores and learning curves of the two beginner groups were compared with those of the expert group using a biosimulation model was used. RESULTS: Each participant improved significantly during the 1-week course. Mean scores on the first day in groups 1-3 were, respectively, 26.7+/-10.7, 33.4+/-5.3, and 72.0+/-5.8, and on day 6 they were 62.2+/-6.6, 63.4+/-7.6, and 86.6+/-4.3. The difference between group 3 and the other two groups was significant but not that between groups 1 and 2. CONCLUSIONS: Training in endoscopy can be assessed using our training model and our scorecard protocol, which distinguishes between various levels of experience. In physicians beginning in the field of gastrointestinal endoscopy this approach could help to reduce risks to patients, shorten learning curves, and exclude unskilled individuals from further fruitless interventions.

Animals↗
PubMed2002

[The effectiveness of HAART. Good planning assures long-term success].

Highly active antiretroviral therapy (HAART) leads to a reduction in the risk of HIV-associated disorders within a matter of months. Response to treatment and the permanency of optimal viral suppression, however, are clearly limited. In the meantime, the major factors responsible for the therapeutic effect have been identified. If appropriate consideration is given to these factors, effective and truly long-term treatment becomes possible. With foresighted treatment planning, an estimated 80% of the patients will experience optimal viral suppression over a period of at least 6 years with the currently available drugs.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Phase I dose-escalating study of raltitrexed ('Tomudex') and cisplatin in metastatic non-small cell lung cancer.

BACKGROUND: The aim of this Phase I, dose-escalation study was to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicity (DLT) of a raltitrexed ('Tomudex') and cisplatin combination in patients with previously untreated, metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received raltitrexed (15-min intravenous infusion), followed by cisplatin (1-h intravenous infusion), every 3 weeks at escalating dose levels. RESULTS: In total, 21 patients entered the study. No DLT was observed up to dose level 4 (raltitrexed 3.0 mg/m(2) plus cisplatin 80 mg/m(2)), or in the first 3 patients who received dose level 5 (raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2)). However, 1 patient, entered at dose level 6 (raltitrexed 4.0 mg/m(2) plus cisplatin 80 mg/m(2)) experienced severe toxicity (including grade 3 diarrhea), and no further patients were recruited at this level. Of 4 additional patients who received raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2), 3 also experienced DLTs. The most common adverse events included nausea/vomiting, asthenia, diarrhea, and hematologic toxicities. Of 19 patients evaluated for response, 3 achieved a partial response, 13 had stable disease, and 3 progressed. CONCLUSIONS: The MTD is raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2), and the RD for future studies is raltitrexed 3.0 mg/m(2) plus cisplatin 80 mg/m(2); DLTs were diarrhea and asthenia. The combination of raltitrexed and cisplatin shows clinical activity in patients with metastatic NSCLC.

Aged↗
PubMed2002

A phase II EORTC study of temozolomide in patients with malignant pleural mesothelioma.

The aim of this study was to investigate the anti-tumour activity of temozolomide in patients with malignant pleural mesothelioma. 27 chemotherapy-naïve patients with histologically-proven malignant mesothelioma were treated with temozolomide 200 mg/m2/day, given orally on days 1-5 of each 28-day cycle. Therapy continued up to 10 cycles unless disease progression or excessive toxicity mandated discontinuation. Toxicity, symptom improvement and pain intensity were regularly assessed. With a median relative dose intensity of 97%, toxicity was moderate with grade 3 or more nausea, vomiting, thrombocytopenia, leucocytopenia, neutropenia, febrile leucocytopenia, arthralgia, infection and fever with infection occurring in 13, 13, 10, 3, 7 and 3% of patients for the remaining events, respectively. Overall, 1 objective response was observed (response rate 4%, 95% Confidence Interval (CI): 0.1-19). Median survival was 8.2 months. Symptom assessment showed no improvement and an increase of pain was observed during the study. Thus, oral temozolomide is an inactive agent in malignant mesothelioma.

Adult↗
PubMed2001

[Resistance in HIV therapy. Which cases profit from resistance testing].

Although resistance tests are widely recommended, definitive and convincing data on the indication for, and the potential benefits of, such tests are not available. In the present article, the major basics and data of importance for the use of such tests in the clinical setting are presented and discussed. Resistance is not a routine investigation, but in specific cases it could lead to an improvement in the selection of the (optimal) antiretroviral drug. In the majority of cases, however, in particular in the case of multiple pretreated patients, little benefit is to be expected. In any case, a specialist should be available prior to and following such testing. Many questions will be answered only after further prospective studies.

Anti-HIV Agents↗
PubMed2001

Procalcitonin as a parameter of disease severity and risk of mortality in patients with Plasmodium falciparum malaria.

The serum levels of procalcitonin (PCT) in Plasmodium falciparum malaria were evaluated for clinical significance in 66 nonimmune and semi-immune patients. Of the 66 patients, 36 had uncomplicated malaria, 24 had severe and complicated malaria, and 6 had fatal malaria (5 from previous studies). Pretreatment PCT concentrations were closely correlated with parasitemia. Concentrations were lowest in semi-immune patients with uncomplicated malaria, compared with those in nonimmune patients (geometric mean concentrations [GMCs], 1.07 and 2.37 ng/mL, respectively), and were highest in severe and complicated cases (GMC, 10.67 ng/mL; P<.001 among all subgroups). Six of 7 patients with PCT concentrations >25 ng/mL died. PCT concentrations decreased on day 2 of treatment in survivors but not in patients with fatal outcome. Thus, repeated PCT measurements may provide useful prognostic information, especially in medical centers that are not experienced in parasite density determination.

Biomarkers↗
PubMed2001

Chemotherapy for advanced non-small cell lung cancer.

The role of chemotherapy in the treatment of non-small cell lung cancer has increased greatly over the past few years. One of the main reasons for the increased acceptance of chemotherapy has been the development of new agents with unique mechanisms of action and high single-agent activity, combined with favorable toxicity. Cytotoxic drugs currently are not only used as single agents or in combination for first- and second-line therapy to achieve palliation in locally advanced and metastatic disease, but also have been incorporated into multimodality treatment strategies for early stage non-small cell lung cancer. This report, however, focuses on the use of chemotherapy in advanced disease. Semin Oncol 28 (suppl 7):1-6.

Antineoplastic Agents↗
PubMed2001

Challenging the platinum combinations: docetaxel (Taxotere) combined with gemcitabine or vinorelbine in non-small cell lung cancer.

The limited single-agent activity of cisplatin, its toxicity profile, and the inconvenience involved in hydrating patients has compelled researchers to investigate other treatments as possible alternative therapies in non-small cell lung cancer. More recently, interest has focused on the potential of nonplatinum combinations. Phase II studies show that the combination of docetaxel (Taxotere; Aventis, Antony, France) and gemcitabine is active in stage IIIB/IV non-small cell lung cancer not previously treated by chemotherapy. Response rates of up to 54% and a median survival time of 13 months have been reported. These data are comparable with the achievements of cisplatin-based combinations. A randomized phase II trial of docetaxel plus gemcitabine versus docetaxel plus cisplatin found that the two regimens were equally active in terms of response rate, median, and 1-year survival. However, the combination of docetaxel with gemcitabine produced significantly less neutropenia and nonhematologic toxicities. In combination, from 80% to 100% of the full single-agent gemcitabine and docetaxel doses can safely be administered once every 3 weeks. The combination of docetaxel plus vinorelbine is also active in non-small cell lung cancer and preliminary data suggest that this schedule with prophylactic filgrastim may optimize tolerability and dose intensity. In a phase II study using this approach, a confirmed response rate of 51% was obtained in 35 patients. At 12 months, the predicted median survival is 14 months and the predicted 1-year survival rate is 60%. Excessive lacrimation, fatigue, and onycholysis were cumulative toxicities. However, the incidence of mucositis and neuropathy was low with the combination of docetaxel and vinorelbine. Docetaxel combined with other new agents, particularly gemcitabine, may offer another useful alternative to cisplatin-based chemotherapy in patients with good performance status.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Chemotherapy for advanced non-small cell lung cancer: standards.

For non-small cell lung Cancer (NSCLC) patients in good clinical condition (PS 0-1), Platin-based combination chemotherapy is currently recommended to prolong survival, prevent or reduce tumor-related symptoms, and maintain the quality of life. Nonetheless, the clinical availability of newer cytotoxic drugs has considerably increased the chemotherapeutic options for Platin-based chemotherapy and, at the same time, increased the difficulties in choosing the most appropriate regimen. These difficulties became especially clear when oncologists were confronted with the disappointing results from ECOG 1594, a study which tested four popular Platin-based combinations. Since no survival advantages could be shown by any of the four combinations used in ECOG 1594, one of the pertinent question seems to be whether, and in what form, a Platin-free combination regimen with newer agents should replace the currently recommended Platin-based therapy? A strong indication that non-Platin-containing regimens are not inferior came from at least two randomized trials. However, first results from EORTC 08975 -trial, did not confirm these observations, since the trend seems to be towards better results for the patients on Platin-containing regimens. A number of trials have shown that patients with PS >1 do not benefit from combination regimens. For these and for elderly patients, single agent therapy with newer cytotoxic agents may be for various reasons an attractive chemotherapeutic alternative for palliation. Several cooperative studies have proven that single agent therapy is superior to best supportive care. Vinorelbine was the first new agent tested in randomized, controlled trials in the elderly population, and was found to give statistically significant survival advantages in comparison to best supportive care only. As chemotherapy gains wider acceptance for advanced and early stage NSCLC, the need for an effective second-line chemotherapy is also growing. On the basis of two randomized, phase III studies, Docetaxel has recently become the first cytotoxic agent to be registered for second-line therapy in NSCLC. Both studies demonstrated that Docetaxel 75 mg/m2 given every 3 weeks significantly prolongs survival, and offers clinically meaningful benefits to patients who have an acceptable performance status.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Chemotherapy in Stage I/II NSCLC and projects of the EORTC-Lung Cancer Group for Early Stage Lung Cancer.

The utilization of systemic chemotherapy within multi-modality treatment concepts in early stage NSCLC would seem to be a very promising concept, which potentially could lead to increased survival rates. It must be noted, however, that application of multi-modality treatment strategies in Stage I and II NSCLC is still experimental and should only be applied within clinical trials. Caution is thus advisable because the existing data are not conclusive and there still are a great number of questions to be answered concerning at least: (1) the regimen, the intensity, the duration of therapy and the most appropriate schedule to be used for chemotherapy, (2) the most appropriate time for surgery and its extensiveness, and (3) the time, dose, and best application modus for radiotherapy. The Lung Cancer Group of the EORTC has been active in the clinical development of multi-modality treatment strategies to improve treatment results for patients with localized, early NSCLC and presently offers its members several attractive studies dealing with induction preoperative chemotherapy, induction preoperative chemo-radiotherapy, and sequential/concomitant chemo-radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Gemcitabine plus etoposide in chemonaive extensive disease small-cell lung cancer: a multi-centre phase II study.

BACKGROUND: Both gemcitabine and etoposide are active in the treatment of small-cell lung cancer (SCLC), and are characterised by mild toxicity profiles. The combination of both drugs was found to be feasible and active in a phase I dose-finding study in solid tumours. Therefore, a phase II trial was initiated to examine the activity and toxicity of this schedule in extensive disease SCLC. PATIENTS AND METHODS: Forty-two chemo-naïve extensive disease SCLC patients were enrolled to receive gemcitabine 1000 mg/m2, days 1, 8 and 15, and etoposide 80 mg/m2, days 8, 9 and 10 of a 28-day cycle. RESULTS: Thirty-seven patients were evaluable for efficacy (five received less than one cycle). No complete responses were observed, but partial responses were seen in 17 patients, yielding an overall response rate of 46%. The median duration of response was 5.8 months. Disease stabilisation was obtained in another 10 patients (27%). The median survival of the 37 protocol-qualified patients was 10.5 months (95% confidence interval (CI): 7.5-12.0). The levels of WHO grade 3 and 4 toxicities were low and clinically manageable. CONCLUSION: In comparison with standard platinum-based regimens, this combination of gemcitabine and etoposide resulted in a somewhat lower response rate, but a similar median survival time. Haematological toxicity was more pronounced than expected from the toxicity data of each agent individually. However, because of its mild non-haematological toxicity, and its ability to be administered in an outpatient setting, this combination provides a reasonable palliative option for patients with extensive disease SCLC.

Adult↗
PubMed2001

[Usefulness of stress echocardiography for early diagnosis of anthracycline-induced cardiomyopathy].

BACKGROUND: Early evidence of drug induced cardiomyopathy is of great importance in oncological treatment, especially for application of Anthrazyklines. Stress echocar-diography (SE) has been proven to be of value in determining left ventricular function at rest and under stress. This study was performed to investigate the cardiac function under Anthrazykline-chemotherapy (aCT). PATIENTS AND METHODS: Patients with malignant thoracic tumors and indication for aCT underwent pharmacological SE (infusion of increasing dobutamin-doses, 5 microgram/kg/bw in 3 minute-steps) before starting aCT. Left ventricular ejection fraction (LVEF) and wall motion were measured. If the tumor decreased and the patients underwent 4 or more cycles of CT, at the end of the last CT another SE investigation was performed. RESULTS: 30 patients (20 men, 15 women; mean age 52, range 28 - 71) were included and the data were compared. Before aCT the mean LVEF was 59 % at rest and 71 % at maximum load, no disturbances of wall motion could be observed. After the end of aCT (mean dose 408 mg, range 256 - 549; mean 4.4 cycles, range 4 - 7) the LVEF was 58 at rest and 68 at maximum load (not significant) and there were also no disturbances of motion. CONCLUSION: SE is an alternative to echocardiography at rest in assessment of left ventricular function in patients receiving Anthrazykline-CT. With the doses applied no patient developed cardiomyopathy. So we consider SE a cost-effective method and safe for patients.

Adult↗
PubMed2001

Endobronchial ultrasound (EBUS)--assessment of a new diagnostic tool in bronchoscopy for staging of lung cancer.

BACKGROUND AND OBJECTIVE: Conventional imaging procedures proved to be insufficient for staging of lung cancer, especially with respect to N-stage, infiltration of mediastinal structures, and early lung cancer. As also the view of the endoscopist is restricted, we developed the new method of endobronchial ultrasonography (EBUS) as an adjunct to conventional bronchoscopy. The initial technical problems were solved by development of a balloon catheter for application of miniaturized 20-MHz probes. PATIENTS AND METHODS: Between January and December, 1999 all patients with an indication for bronchoscopy and additional EBUS were documented prospectively. RESULTS: In 648 patients we used additional EBUS. Of these, 242 (37%) were female and 406 (63%) were male. The mean age was 49.2 (range 0-83) years. The mean procedure time for the bronchoscopies was 18.9 (range 5.7-38.9) min, and the mean time for EBUS was 6.3 (range 3.1-14.4) min. Side effects were comparatively rare. 34 patients (5%) needed supplementary oxygen during the examination, the others tolerated EBUS without any desaturation. CONCLUSION: EBUS is a new technology that can be easily applied and is well tolerated. It improves the results of bronchoscopy in addition to conventional diagnostic procedures. Further developments will be made in future to improve the application of ultrasound in chest medicine.

Adolescent↗