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Biomedical subjects

C Manegold

Publications and source records attributed to C Manegold.

At least 55 records · Page 3Linked to original sources
PubMed2001

Treatment of elderly patients with non-small-cell lung cancer.

One of the main reasons for the increased acceptance of chemotherapy for both early and advanced non-small-cell lung cancer is the clinical availability of several new cytotoxic drugs. These less toxic, yet highly effective, new drugs not only benefit younger patients, but also offer new treatment opportunities for the elderly; advanced age alone should not preclude appropriate cytotoxic therapy. Vinorelbine (Navelbine) was the first new agent tested in randomized trials with elderly patients having advanced non-small-cell lung cancer. Results proved that vinorelbine does indeed have a survival advantage over best supportive care for these patients. Gemcitabine (Gemzar) is probably the most effective cytotoxic agent in the treatment of non-small-cell lung cancer today, showing high antitumor activity as a single agent and in combination. Moreover, it has a favorable toxicity profile. Since it can be effectively used for the palliation of tumor-related symptoms and can thus positively influence performance status, gemcitabine may be of great clinical importance in the treatment of elderly and unfit patients. Docetaxel (Taxotere) has recently become the first agent to be registered for second-line chemotherapy in non-small-cell lung cancer. This decision was based on survival advantages and clinical benefit data stemming from two randomized phase III studies. Nonetheless, chemotherapy for elderly patients continues to be a major unresolved oncologic problem. Clinical research with the new cytotoxic agents should be intensified to further define the most appropriate use for these drugs as single agents or in combination for the treatment of elderly patients.

Age Factors↗
PubMed2000

Reactivation of hepatitis B virus replication accompanied by acute hepatitis in patients receiving highly active antiretroviral therapy.

We describe 2 patients who were initially positive for antibodies to hepatitis B surface antigen and who experienced a strong and sudden increase of hepatitis B virus (HBV) replication during highly active antiretroviral therapy (HAART). We found that reactivation of HBV replication during HAART can occur independently of lamivudine resistance or withdrawal of lamivudine, and in spite of increasing CD4(+) cell counts.

AIDS-Related Opportunistic Infections↗
PubMed2000

[Pathogenesis of HIV infection as the key to eradication? New therapeutic approaches].

While the effectiveness of conventional antiviral treatment is well proven, its limitations are becoming more and more evident. New approaches are resulting from the "decoding" of the pathogenesis of HIV infection. Thus, for example, experimental studies are looking at drug-induced blockade of the co-receptors necessary for the infection of the target cells. Treatment can be applied at all stages of viral replication. So far, reverse transcriptase and protease inhibitors have been employed. Other strategies are aimed at immunostimulation (e.g. with interleukin 2) and immunosuppression (cortisone, hydroxyurea). The development of therapeutic vaccines is difficult, but prophylactic vaccines hold out greater promise; field trials are underway.

AIDS Vaccines↗
PubMed2000

[Differential indications for induction therapy of non-small-cell lung tumors].

Induction chemotherapy and induction chemo-radiotherapy have shown their efficiency and feasibility in many phase-II studies and have profen superior to operation alone in stage IIIa of NSCLC in several phase-III studies. Therefore it is justified to recommend this multimodal therapy in stage IIIa N2 disease within clinical studies. However, it is currently not justified to present this multimodal treatment modality as a generally agreed standard.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Gemcitabine in non-small cell lung cancer (NSCLC).

The role of chemotherapy in the treatment of non-small cell lung cancer (NSCLC) has increased greatly in the past few years. While cytotoxic drugs are currently used both as single agents and in combination for palliation in locally advanced and metastatic disease, they have also been incorporated into multi-modality treatment strategies of Stage I to Stage III NSCLC. One of the main reasons for the increased acceptance of chemotherapy is the development of new substances. Among the most promising of these new drugs is the antimetabolite gemcitabine. Several single-arm gemcitabine Phase II studies involving more than 400 patients show validated response rates in more than 20% of the patients. These positive results have also been confirmed in randomized Phase II studies. Gemcitabine's unique mechanism of action, its lack of overlapping toxicity with other agents, and its favorable toxicity profile also define it as an ideal candidate for combination therapy. The activity seen with single-agent gemcitabine therapy can be compared with that of cisplatin-etoposide combination therapy. Gemcitabine-cisplatin combination response rates range from 31% to 54%, with a median survival time between 8.4 and 15.4 months and a 1-year survival rate between 30% and 59%. In addition to the clinical research of gemcitabine-cisplatin combinations, gemcitabine has also been tested in various double and triple combinations with carboplatin, paclitaxel, docetaxel, vinorelbine, and ifosfamide. Investigations combining gemcitabine with radiation therapy are on-going. The following review will summarize results from representative Phase I/II and III studies using gemcitabine for NSCLC patients.

Animals↗
PubMed2000

Front-line treatment of advanced non-small-cell lung cancer with MTA (LY231514, pemetrexed disodium, ALIMTA) and cisplatin: a multicenter phase II trial.

BACKGROUND: To evaluate the activity of MTA plus cisplatin in chemotherapy-naive patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-six chemotherapy-naïve patients with NSCLC received 500 mg/m2 MTA plus 75 mg/m2 cisplatin every 21 days, with 4 mg dexamethasone orally twice daily on the day before, of, and after MTA administration. RESULTS: Median age was 58 years. WHO performance status was 0-2. Eighteen patients each had stage IIIB and IV disease. Seventeen patients each had squamous-cell and adenocarcinoma; two had undifferentiated disease. Fourteen patients (39%; 95% confidence interval: 23%-57%) showed partial response; seventeen (47%) had stable disease. Median survival was 10.9 months. Twenty-one patients (59%) experienced grade 3 or 4 granulocytopenia without fever or infection. Five (14%) and six (17%) patients experienced grade 3 anemia and grade 3 or 4 thrombocytopenia, respectively. Nonhematological toxicities included grade 3 nausea in two patients (6%), and grade 3 and 4 diarrhea in one patient (3%) each. One patient each experienced grade 4 ALT and grade 3 bilirubin and AST elevations. CONCLUSIONS: MTA plus cisplatin is well tolerated and active against NSCLC. Further studies of this combination are warranted.

Adult↗
PubMed2000

Comparative evaluation of two branched-DNA human immunodeficiency virus type 1 RNA quantification assays with lower detection limits of 50 and 500 copies per milliliter.

We have comparatively evaluated Quantiplex version 3.0 and version 2. 0 on 133 plasma samples and a repetitive dilution series. Version 3. 0 yielded higher human immunodeficiency virus RNA values, and the ratio of version 3.0 results to version 2.0 results decreased from 3. 47 below 1,000 copies/ml to 1.97 above 50,000 copies/ml [linear regression, log (version 3.0) = 0.915 + 0.871 x log (version 2.0); r(2) = 0.952].

DNA Probes↗
PubMed2000

Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer.

PURPOSE: The Hoosier Oncology Group has previously reported the results of its phase II trial of the combination of cisplatin plus gemcitabine. In that study of 27 assessable patients with advanced or metastatic non-small-cell lung cancer (NSCLC), the response rate was 33%, with a median survival of 8.4 months. Based on such favorable results, the Hoosier Oncology Group designed this randomized phase III study of gemcitabine plus cisplatin compared with cisplatin alone in chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Patients were randomized to receive either cisplatin (100 mg/m(2) intravenously on day 1 of a 28-day cycle) or the combination of cisplatin (100 mg/m(2) intravenously on day 1) plus gemcitabine (1,000 mg/m(2) administered intravenously on days 1, 8, and 15 of a 28-day cycle). RESULTS: From August 1995 to February 1997, 522 assessable chemotherapy-naive patients were randomized. Toxicity was predominantly hematologic and was more pronounced in the combination arm, with grade 4 neutropenia occurring in 35.3% of patients compared with 1.2% of patients on the cisplatin monotherapy arm. The incidence of neutropenic fevers was less than 5% in both arms. Grade 4 thrombocytopenia occurred in 25. 4% of patients on the combination arm compared with 0.8% of patients on the cisplatin monotherapy arm. No serious hemorrhagic events related to thrombocytopenia were reported for either arm. The combination of gemcitabine plus cisplatin demonstrated a significant improvement over single-agent cisplatin with regard to response rate (30.4% compared with 11.1%, respectively; P <.0001), median time to progressive disease (5.6 months compared with 3.7 months, respectively; P =.0013), and overall survival (9.1 months compared with 7.6 months, respectively; P =.004). CONCLUSIONS: For the first-line treatment of NSCLC, the regimen of gemcitabine plus cisplatin is superior to cisplatin alone in terms of response rate, time to disease progression, and overall survival.

Adult↗
PubMed1999

A Phase II study of gemcitabine in patients with malignant pleural mesothelioma. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

BACKGROUND: Gemcitabine has shown activity in patients with less chemosensitive solid tumors. Phase II screening of novel drugs is an accepted method with which to investigate new therapies in malignant mesothelioma. The European Organization for Research and Treatment of Cancer-Lung Cancer Cooperative Group has performed several sequential Phase II trials of new agents for the treatment of mesothelioma over the last 10 years. METHODS: Twenty-seven chemotherapy-naive patients with histologically proven malignant mesothelioma were treated with gemcitabine as a 30-minute intravenous administration of 1250 mg/m2 on Days 1, 8, and 15 of a 28-day cycle. Therapy continued for up to ten cycles unless disease progression or excessive toxicity mandated discontinuation. RESULTS: With a median relative dose intensity of 96%, toxicity was mild and neutropenia of > or = Grade 3 (according to National Cancer Institute criteria) occurred in 30% of patients, without episodes of febrile neutropenia. One case of hemolytic-uremic syndrome, most likely related to gemcitabine use, was observed. Overall, 2 objective responses were observed (response rate of 7%; 95% confidence interval, 1-24%). The median survival was 8 months. CONCLUSIONS: At the prescribed dosage and schedule, single agent gemcitabine appears to have limited activity in chemotherapy-naive patients with malignant pleural mesothelioma.

Adult↗
PubMed1999

Prior cytomegalovirus infection and the risk of restenosis after percutaneous transluminal coronary balloon angioplasty.

BACKGROUND: Restenosis is a common problem after all revascularization procedures in atherosclerotic coronary arteries. Reactivated human cytomegalovirus (CMV) has been detected in tissues of restenotic vascular lesions and was hypothesized to be a contributing pathogenic factor. Recent data suggest an association of restenosis after optimal coronary atherectomy with CMV serostatus, and a possible role of antiviral therapy was discussed. We therefore tested the hypothesis that prior CMV infection might be a risk factor for restenosis after conventional coronary balloon angioplasty (PTCA). METHODS AND RESULTS: We analyzed 92 consecutive patients who had been admitted for control angiography after previous PTCA within a mean interval of 6 months. Anti-CMV antibodies were measured as an indicator of prior CMV infection and latency. The coronary angiograms before PTCA, directly after, and 6 months later were analyzed quantitatively. Sixty-five percent of the patients were CMV-positive. Before PTCA, the degree (mean+/-SD) of stenosis was 69+/-10% in CMV-positive and 68+/-8.3% in CMV-negative subjects. PTCA resulted in a residual stenosis of 39% in both groups. After 6 months, the late losses of luminal diameter in the CMV-positive and -negative groups were 11+/-13% and 12+/-15%, respectively (P=0.658). In an ANCOVA with 25 potential risk factors for restenosis, CMV serostatus was not significantly associated with restenosis development. CONCLUSIONS: Our data indicate that prior CMV infection, in contrast to optimal atherectomy, is not associated with chronic restenosis after conventional coronary balloon angioplasty. The results do not support a possible benefit from antiviral therapy.

Adult↗
PubMed1999

Mediastinal B-cell lymphoma: a study of its histomorphologic spectrum based on 109 cases.

Mediastinal B-cell lymphoma (MBL) is a distinct variant of aggressive non-Hodgkin's lymphoma with characteristic clinical and biological features but less well-defined histomorphology. We reevaluated 124 biopsy specimens from 109 MBL patients of an Italian/French/German retrospective clinical study. MBL was primarily diagnosed on clinical and histological grounds in conjunction with the detection of CD20 expression by immunohistology. Cytologically, MBL features limited intralesional but considerable interindividual cytological diversity, ranging from medium-sized to very large, atypical cells. Sclerosis and necrosis are restricted to extrathymic and extranodal sites of involvement, predominantly the lung, as is angioinvasion, which predominantly affects larger vessels. The medium-sized and the large cell variants resemble marginal zone lymphoma variants, whereas the very large cell variant of MBL has not so far been found to have any extramediastinal counterpart. We conclude that MBL displays a broad morphological spectrum covering more than is implied by the term "diffuse large cell lymphoma." Because statistical analysis of cytological and histological criteria failed to correlate with prognosis in this comprehensive group of patients, we think it inadvisable further to subclassify MBL.

Humans↗
PubMed1999

Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer.

This randomized study was designed to determine the response rates, survival and toxicities of single-agent gemcitabine (GEMZAR) and a combination of cisplatin/etoposide in chemonaive patients with non-resectable, locally advanced or metastatic non-small cell lung cancer (NSCLC). Gemcitabine 1000 mg/m2 was given as a 30-min intravenous infusion on days 1, 8, 15 of a 28-day cycle, cisplatin 100 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1 (following cisplatin), 2 and 3. Major eligibility criteria included histologically confirmed non-small cell lung cancer, measurable disease, Zubrod performance status 0-2, no prior chemotherapy, no prior radiation of the measured lesion, and no CNS metastases. One hundred and forty-seven patients were enrolled, 72 in the gemcitabine and 75 in the cisplatin/etoposide arm. Patient characteristics were well-matched across both arms. Sixty-seven gemcitabine and 72 cisplatin/etoposide patients were qualified for efficacy analysis. There were no complete responses, but 12 partial responses in the gemcitabine arm and 11 in the cisplatin/etoposide arm, for protocol-qualified response but 12 partial responses in the gemcitabine arm and 11 in the cisplatin/etoposide arm, for protocol-qualified response rates of 17.9% (95%, CI: 9.6-29.2%,) and 15.3% (95% CI: 7.9-25.7%,), respectively. Median survival times were 6.6 months (95% CI: 4.9-7.3 months) for gemcitabine and 7.6 months (95% CI: 5.4-9.3 months) for cisplatin/etoposide. The 1-year survival probability estimate was 26% for gemcitabine and 24% for cisplatin/etoposide. There were no statistically significant between-group differences in time-to-event measures, but patients in the gemcitabine arm had a greater probability of achieving a tumour response after 2 months (probability estimate: 8 vs. 0%,) and of the response lasting at least 6 months (73 vs. 45%,). Clinical and haematologic toxicity was more pronounced in the cisplatin/etoposide arm. Quality-of-life measures indicated a significant worsening of symptomatology in the cisplatin/etoposide arm for hair loss, nausea and vomiting, and appetite loss. This randomized study provides further evidence that single-agent gemcitabine is an active and effective therapy for patients with non-resectable. locally advanced or metastatic NSCLC and good performance status, and that it is better tolerated than the combination cisplatin/ etoposide.

Adult↗
PubMed1999

Serum parathyroid hormone-related protein levels and response to bisphosphonate treatment in hypercalcemia of malignancy.

The pathogenesis of hypercalcemia of malignancy comprises increased net bone resorption and enhanced renal tubular reabsorption of calcium (Ca). To evaluate the prevalence of an increased renal tubular reabsorption of Ca index [tubular reabsorption of calcium index (TRCaI)] in cancer patients with hypercalcemia and of elevated circulating levels of PTH-related protein (PTHrP), which is recognized as a major mediator of this syndrome, we investigated 315 well rehydrated patients, aged 58.1 +/- 0.7 yr (mean +/- SEM), with hypercalcemia [albumin-corrected plasma Ca (pCa), >2.7 mmol/L] secondary to histologically proven malignancy. Changes in pCa and, therefore, various Ca filtered loads were obtained by different degrees of bone resorption inhibition achieved with a single infusion of the bisphosphonate ibandronate, given at various doses on a randomized, double blind basis. PTHrP was determined at baseline in 147 of the patients and 7 days after bisphosphonate therapy in 73. Before ibandronate therapy, pCa was 3.36 +/- 0.02 mmol/L, mean TRCaI was increased at 3.09 +/- 0.03 mmol/L glomerular filtration rate (GFR; normal, 2.40-2.90), and 65% of patients had TRCaI above 2.90 mmol/L GFR. Mean serum PTHrP levels were 4.9 +/- 0.5 pmol/L (normal, <2.5) and values above the normal range were found in 53% of the patients (76% in lung and upper respiratory tract malignancies). By 7 days after the infusion of ibandronate, a decrease in pCa of 0.69 +/- 0.03 mmol/L (20.0 +/- 0.7%; P < 0.001) and in bone resorption [mean change in fasting urinary Ca, 0.09 +/- 0.04 mmol/L GFR (47.6 +/- 8.6%; P < 0.001) and 14.4 +/- 1.7 nmol/mmol (27.6 +/- 10.6%; P < 0.01) in deoxypyridinoline] was observed. TRCaI was slightly lowered by 0.30 +/- 0.09 mmol/L GFR. Mean changes in PTHrP, 1,25-dihydroxyvitamin D3, and PTH were +0.7 +/- 0.4 (P = NS), +27.6 +/- 3.0 (P < 0.001), and +2.9 +/- 0.8 (P < 0.005) pmol/L, respectively. After ibandronate treatment, the relative risk of relapsing hypercalcemia was particularly increased (3.43-fold) in lung and upper respiratory tract malignancies. These results obtained in a large cohort of patients indicate a significant prevalence of an increased renal tubular reabsorption of calcium index in hypercalcemia of malignancy and a substantial proportion of patients with detectable PTHrP.

Absorption↗
PubMed1999

Docetaxel (Taxotere) in non-small cell lung cancer: ongoing studies in Heidelberg and future plans.

Docetaxel (Taxotere, Rhône-Poulenc Rorer, Antony, France) as a "stabilizing antitubulin" has in the last few years gained the reputation of being one of the most effective cytotoxic drugs in the therapy of non-small cell lung cancer. Clinical investigations of docetaxel in non-small cell lung cancer continue and currently focus on new combination chemotherapy regimens, its simultaneous use in combination with radiotherapy, as well as trials within multimodality treatment concepts. Our hospital's direct experiences with docetaxel include its sequential use with gemcitabine in single-agent therapy and a phase I study combining docetaxel with ifosfamide. In addition we are planning a randomized study to test docetaxel within a sequential and concomitant chemoradiotherapy concept in patients with inoperable stage III non-small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Docetaxel (taxotere): current status of clinical development in non-small-cell bronchial carcinoma (NSCLC)].

BACKGROUND: Docetaxel (Taxotere) as a "stabilizing antitubulin" has in the last few years gained the reputation of being one of the most effective cytotoxic drugs in the therapy of NSCLC. Up until now it has primarily been used in clinical studies for both single agent- and combination chemotherapy being tested in a variety of different treatment regimens not only for advanced disease but also for early stage NSCLC. RESULTS OF STUDIES: Clinical investigations of Docetaxel in NSCLC continue and currently focus upon randomized studies, new combination chemotherapy regimens, its simultaneous use in combination with radiotherapy as well as trials within multi-modality treatment concepts. The preliminary results of these studies underline the importance of Docetaxel for NSCLC and confirm the positive results stemming from previous single agent- and combination therapy investigations.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Combined effects of ionizing radiation and 4-hydroperoxyfosfamide in vitro.

BACKGROUND AND PURPOSE: Combined radiochemotherapy has gained increasing interest in clinical applications. The effects of combined exposure of ionizing radiation and 4-hydroperoxyifosfamide (4HOOIF) on cell survival were investigated in vitro. MATERIALS AND METHODS: Clonogenic survival of log phase V79, Caski (squamous carcinoma), Widr (colon carcinoma) and MRI-221 cells (human melanoma) was determined after combined exposure to 4HOOIF and radiation. Measurement of cell survival for different cell cycle phases was performed after mitotic shake-off (V79) or appropriate intervals after serum stimulation of plateau phase cells (Widr). Control of cell cycle distribution was performed using flow cytometry. RESULTS: In all cell lines tested, a combined exposure resulted in cell killing that was greater than for independent action. While this type of radiosensitization was of minor magnitude for log-phase cells or cells in G1 substantial radiosensitization was detected for S-phase cells with enhancement ratios (calculated from the respective mean inactivation doses) of up to 1.5. CONCLUSIONS: The results demonstrate the interaction of 4HOOIF and radiation-induced cell damage with marked cell cycle specificity. Since the largest combination effect was observed for the most radioresistant S-phase cells, damage interaction could be mediated by an interference of 4HOOIF with the repair/fixation pathway of radiation-induced potentially lethal damage.

Animals↗