Biomedical subjects

C Manegold

Publications and source records attributed to C Manegold.

At least 19 recordsLinked to original sources

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↗

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↗

PubMed1998

Ifosfamide and gemcitabine: a phase II trial in advanced inoperable non-small cell lung cancer.

The novel nucleoside agent gemcitabine has demonstrated antitumor activity against a variety of solid tumors and is associated with low toxicity. A phase I trial in Germany of gemcitabine combined with the alkylating agent ifosfamide has shown encouraging activity against non-small cell lung cancer. The efficacy and toxicity of this combination was further evaluated in a phase II trial involving chemotherapy-naive patients with non-small cell lung cancer (mostly stage IV disease). Gemcitabine was administered at a dose of 1,000 mg/m2 on days 1, 8, and 15, followed by a 1-week rest, while ifosfamide was given at a dose of 1,500 mg/m2 on days 8 through 12. Fifty-five patients were treated, 49 of whom are evaluable for response. Six patients were not evaluable because they had not received sufficient therapy (less than one complete cycle) because of early disease progression or early death. Twelve patients responded, for an overall objective response rate of 24.5%. The median survival time was 8.9 months, and the 1-year survival rate was 30.9%. Grades 3 and 4 neutropenia occurred in 30.2% and 24.5% of patients, respectively, but the incidence of infection was low. These results indicate that the combination of gemcitabine and ifosfamide is active against non-small cell lung cancer and has a mild toxicity profile, and suggest that further evaluation of this combination is warranted.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Ifosfamide and docetaxel in non-small cell lung cancer.

Ifosfamide has been in use for several decades and is generally considered to be one of the most effective drugs for the treatment of non-small cell lung cancer (NSCLC). At the same time, docetaxel is one of the new, promising drugs with high antitumor activity in various solid tumors. In NSCLC, an objective remission rate of 33% could be achieved in chemotherapy-naive patients. Currently, clinical research with docetaxel in NSCLC patients focuses on various combinations of this drug with radiotherapy and a number of different cytostatic chemicals. There are good reasons for combining docetaxel with ifosfamide. In addition to the promising antitumor activity in NSCLC displayed by both drugs, it is an advantage that docetaxel and ifosfamide have only minimal overlapping nonhematologic toxicity. Moreover, the combination seems to be well founded due to the lack of cross-resistance between docetaxel and alkylators such as ifosfamide of the oxazaphosphorine type, which have shown synergistic antitumor activity in vivo. Based on this background, two phase I studies of docetaxel and ifosfamide have been initiated.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

An update on European randomized studies in non-small cell lung cancer.

Less than 25% of non-small cell lung cancer (NSCLC) patients present with surgically resectable stage I and II disease, and the majority of patients will eventually die of disseminated disease. Cisplatin-based chemotherapy has been shown to prolong survival and improve quality of life in patients with stage III and IV disease. In recent years, new chemotherapeutic agents (eg, gemcitabine, paclitaxel, docetaxel, vinorelbine, and irinotecan) have shown definite activity in advanced NSCLC. The activity of these agents has led to phase II studies combining them with cisplatin, producing response rates that are generally in excess of 35%. Randomized trials suggest that survival is improved when combinations of gemcitabine/cisplatin, vinorelbine/cisplatin, and paclitaxel/cisplatin are compared with cisplatin alone or cisplatin/etoposide. The following report reviews the ongoing trials in NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Single-agent gemcitabine versus cisplatin/etoposide in patients with inoperable, locally advanced, or metastatic non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) remains a malignancy that is refractory to most currently available chemotherapeutic agents. The most frequently used systemic therapy is cisplatin-based combination therapy, which is not always suitable for patients with stage IV disease because of toxicity. Thus, any single agent with a good patient tolerability profile would be a useful alternative for those patients for whom the main purpose of treatment is palliation. The novel nucleoside analog gemcitabine has proven single-agent activity in patients with NSCLC, with consistent response rates of 20% and above. This report reviews two randomized phase II studies of single-agent gemcitabine versus cisplatin/etoposide in patients with advanced NSCLC.

Adult↗

PubMed1998

The causes and prognostic significance of low hemoglobin levels in tumor patients.

BACKGROUND: While the production and degradation of erythrocytes are carefully balanced in healthy persons several processes can lead to an imbalance in tumor patients resulting in anemia. PATHOGENESIS: Processes caused by the tumor itself can lead to a typical "anemia of chronic disease" which is normochromic, normocytic, accompanied by both a reduced number of reticulocytes and reduced iron-binding capacity. In many cases, the erythropoietin response to anemia is insufficient. Cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor seem to be involved in suppressing erythropoiesis by acting on the bone marrow and on erythropoietin production. Anemia can also be the result of cancer therapy, as is particularly prominent in patients with lung cancer receiving chemotherapy (incidence of anemia 20 to 50%). PROGNOSTIC FACTOR: Several studies have demonstrated that anemia is not only linked to an impaired quality of life but to prognosis as well. Albain et al. [2] identified a hemoglobin level of below 11 g/dl as a significant independent prognostic factor associated with shorter survival of chemotherapeutically treated non-small cell lung cancer (NSCLC) patients. The same applies to a hemoglobin level below 12.7 g/dl for radiotherapeutically treated NSCLC patients according to a study by Ohlhauser et al. (Oncology 1997;20:1689-92). Several studies have confirmed this prognostic importance of hemoglobin level for other solid tumors. TREATMENT: To correct anemia, clinicians have several options. Given the risks associated with transfusions, especially for tumor patients, recombinant erythropoietin holds promise for raising hemoglobin levels and thereby improving therapeutic efficacy and survival.

Anemia↗

PubMed1997

[Docetaxel (taxotere) in non-small-cell bronchial carcinoma].

BACKGROUND: Various new drugs with different mechanisms of action are presently under investigation for the field of solid tumors. The taxanes, Taxotere and Taxol, are among those drugs possessing a unique mechanism of action but showing pharmacological differences. CONCLUSION: The results of several phase I and II studies of Taxotere in monotherapy as well as in combination schedules with chemotherapy and Radiotherapy show Taxotere to be active in non small cell lung cancer and build the basis for further evaluation in clinical trials.

Antineoplastic Agents, Phytogenic↗

PubMed1997

Induction of granulocyte colony-stimulating factor by acute febrile infection but not by neutropenia in HIV-seropositive individuals.

The objective of this study was to assess endogenous granulocyte colony-stimulating factor (G-CSF) serum levels in HIV-seropositive individuals with persistent neutropenia or acute febrile infection. Serum levels of G-CSF were measured by enzyme-linked immunoabsorbent assay. HIV-seropositive subjects (n = 28) with afebrile neutropenia (< 1000 neutrophils/microliter) showed low G-CSF serum levels (i.e., median was below the detection limit) not different from those of healthy volunteers (n = 66) or nonneutropenic HIV-seropositive controls (n = 75). In contrast, patients with acute myeloid leukemia and afebrile neutropenia from chemotherapy (n = 17) demonstrated markedly elevated G-CSF levels (median, 264 pg/ml; p < 0.0001). However, HIV-seropositive patients with pneumonia (n = 17) showed increases of G-CSF serum levels (median, 152 pg/ml; p < 0.0001) similar to HIV-seronegative patients (n = 17) with pneumonia (median, 123 pg/ml; p = 0.97). The results suggest that there may be a contribution of low G-CSF serum levels to persistent neutropenia in HIV-seropositive individuals. Moreover, the different G-CSF serum levels in HIV-seropositive individuals in response to neutropenia or acute febrile inflammation suggest different mechanisms for the regulation of G-CSF.

Acute Disease↗

PubMed1997

Single-agent gemcitabine versus cisplatin-etoposide: early results of a randomised phase II study in locally advanced or metastatic non-small-cell lung cancer.

BACKGROUND: This randomised study was designed to determine the response rate survival and toxicity of single-agent gemcitabine and cisplatin-etoposide in chemo-naïve patients with locally advanced or metastatic non-small-cell lung cancer. PATIENTS AND METHODS: Gemcitabine 1,000 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 PS 0-2; no prior chemotherapy, no prior radiation of the measured lesion, and no CNS metastases. RESULTS: 146 patients were enrolled, 71 patients on gemcitabine and 75 patients on cisplatin-etoposide. Patient characteristics were well matched across both arms. Sixty-six gemcitabine patients and 72 cisplatin-etoposide patients were evaluable. Partial responses were seen in 12 gemcitabine patients (18.2%; 95% CI: 9.8-30) and 11 cisplatin-etoposide patients (15.3%; 95% CI: 7.9-25.7). Early indications show no statistical differences between the two treatments with respect to time to disease progression or survival. Haematological and laboratory toxicity were moderate and manageable. However, hospitalisation because of neutropenic fever was required for 6 (8%) cisplatin-etoposide patients but not for any gemcitabine patients. Non-haematological toxicity was more pronounced with significant differences in nausea and vomiting (grade 3 and 4: 11% gemcitabine vs. 29% cisplatin-etoposide; despite the allowance for 5-HT3 antiemetics during the first cycle of cisplatin-etoposide), and alopecia (grade 3 and 4:3% gemcitabine vs. 62% cisplatin-etoposide). CONCLUSIONS: In this randomised study, single-agent gemcitabine was at least as active but better tolerated than the combination cisplatin-etoposide.

Adult↗

PubMed1997

Invasive thymoma: treatment with postoperative radiation therapy.

PURPOSE: To assess radiation therapy and chemotherapy in the treatment of invasive thymoma and thymic carcinoma. MATERIALS AND METHODS: In 1981-1995, 43 patients received irradiation after total (n = 23) or subtotal (n = 20) resection. Tumors were thymic carcinoma (n = 10) or invasive thymoma (n = 33). Masaoka stage was II in 10 patients, III in 14, and IV in 19. Median total dose applied was 50 Gy (range, 10-72 Gy). Seventeen patients (five with stage III and 12 with stage IV) also received chemotherapy. RESULTS: Patients with thymic carcinoma had a median survival of 9.5 months, compared with 50 months for patients with invasive thymoma (P = .008). Patients' median survival and 5-year survival rates were 97 months and 90% for stage II, 65 months and 67% for stage III, and 32.5 months and 30% for stage IV tumors (P = .024). Overall control rate within the radiation field was 81% (35 patients) and overall local control rate within the thorax was 74% (32 patients). Of the 17 patients who received chemotherapy and radiation therapy, nine had thymic carcinoma and a median survival of 12 months (range, 1.4-23.0 months). CONCLUSION: With total doses of 45-50 Gy, local control is achievable after radical resection. Whether patients with completely resected stage II thymomas should receive radiation after surgery remains uncertain, as does the role of chemotherapy in the treatment of thymoma.

Adult↗

PubMed1997

Treatment outcome and prognostic factors for primary mediastinal (thymic) B-cell lymphoma: a multicenter study of 106 patients.

PURPOSE: To define clinicopathologic features, response to treatment, and prognostic factors of primary mediastinal B-cell lymphoma (MBL), a CD20+ tumor recognized as a distinct entity among non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: One hundred six patients presented with disease confined to thorax (86%), bulky mediastinum (73%), superior vena cava syndrome (47%), and contiguous infiltration (57%). Ninety-nine received doxorubicin-containing chemotherapy (CHT). RESULTS: Thirty-five of 99 patients were primarily CHT-resistant, and 64 responded: 23 achieved complete response (CR) and 41 achieved response with residual mediastinal abnormality. Seventy-seven percent of responders received mediastinal radiotherapy (RT). Of 64 responders, 18 (28%) relapsed: none of 23 CR patients and 18 of 41 (44%) with residual mediastinal abnormality. Relapse-free survival rate of responders was 71% at 3 years. Actuarial 3-year survival rate was 52% for all patients and 82% for responders. Predictive factors of poor outcome were identified by logistic regression; Cox survival analysis was performed on death and relapse. Pericardial effusion (P < .001) and Eastern Cooperative Oncology Group (ECOG) performance status > or = 2 (P = .009) predicted nonresponse (NR) and affected survival. Less than partial midway response to CHT predicted NR to subsequent therapies. Bulky disease was related to persistent mediastinal abnormality and risk of relapse (P = .025). CONCLUSION: MBL is an aggressive NHL with unique clinicopathologic aspects, often refractory to current CHT designed for high-grade NHL. Poor performance status and pericardial effusion predict NR and poor survival. Inadequate response after the first courses of front-line CHT predicts failure of subsequent treatment. Responders with bulky mediastinum or residual mediastinal abnormality after CHT are at risk of relapse. These factors should help to select high-risk patients for intensive treatments.

Adolescent↗

PubMed1997

Primary mediastinal B-cell lymphoma: update of its clinicopathologic features.

The peculiar clinical, histomorphological and biological characteristics of PMBCL are reviewed. Special emphasis is given to the frequent aggressive clinical behaviour of this lymphoma in which conventional prognostic factors seem inadequate to identify high risk cases. The need for new clinical and/or biological prognostic markers is stressed.

Biomarkers, Tumor↗

PubMed1997

A randomized study of gemcitabine monotherapy versus etoposide/cisplatin in the treatment of locally advanced or metastatic non-small cell lung cancer.

This randomized, multinational, multicenter study was designed to determine the response rate of gemcitabine monotherapy and cisplatin/etoposide combination therapy in chemotherapy-naive patients with advanced, recurrent, and/or metastatic non-small cell lung cancer (stage IIIA [if inoperable], IIIB, or IV). One group of patients received gemcitabine 1,000 mg/m2 intravenously once a week for 3 weeks (days 1, 8, and 15) followed by a 1-week rest period. The second group received cisplatin 100 mg/m2 intravenously on day 1 of each 28-day cycle in combination with etoposide 100 mg/m2, administered on days 1, 2, and 3 following the cisplatin infusion. Each patient was allowed to remain on study up to a maximum of six cycles. The planned interim analysis was based on the 117 patients in the study, 116 of whom were randomized up until November 20, 1995. The efficacy analysis was performed on the 107 patients who had data from a minimum of two cycles, whereas the safety analysis was based on data from all 116 randomized patients. In the gemcitabine arm there were 10 of 52 (19%) partial responders; in the cisplatin/etoposide arm there were four (7%) of 54 partial responders. There was a statistically significant difference in the response rates between the two arms, with a 95% confidence interval of 0.6% to 32.1% (P = .040). The median time to progressive disease was 4.2 months for gemcitabine patients and 3.7 months for cisplatin/etoposide patients. There was significantly more alopecia and nausea and vomiting in the cisplatin/etoposide arm compared with the gemcitabine arm, as well as two cases of neutropenic sepsis in the cisplatin/etoposide arm. These data indicate that single-agent gemcitabine is at least as effective as the combination of cisplatin/etoposide in the treatment of advanced non-small cell lung cancer and has an improved safety profile.

Adult↗

PubMed1997

A phase II trial of gemcitabine and ifosfamide in non-small cell lung cancer.

The novel nucleoside agent gemcitabine has demonstrated antitumor activity against a variety of solid tumors and is associated with low toxicity. A phase I trial in Germany of gemcitabine combined with the alkylating agent ifosfamide has shown encouraging activity against non-small cell lung cancer (NSCLC). The efficacy and toxicity of this combination was further evaluated in a phase II trial of chemotherapy-naive patients with NSCLC (mostly stage IV disease). Gemcitabine was administered at a dose of 1,000 mg/m2 on days 1, 8, and 15 followed by a 1-week rest, while ifosfamide was given at a dose of 1,500 mg/m2 on day 8 and days 9 through 12. Fifty-one of 56 patients were evaluable for response. Eleven partial responses were seen, for an overall objective response rate of 22%. The 6- and 9-month survival rates are 62% and 41%, respectively. Grade 3 and 4 neutropenia occurred in 35.8% and 24.5% of patients, respectively, but the incidence of infection was low. These results indicate that the combination of gemcitabine and ifosfamide is active against NSCLC and has a mild toxicity profile, and suggest that further evaluation of this combination is warranted.

Adult↗

PubMed1996

Expression of resistance-related proteins in tumoral and peritumoral tissues of patients with lung cancer.

Twenty tumoral and peritumoral tissues from patients with lung cancer were analyzed immunohistochemically for the drug resistance-related proteins P-glycoprotein (P-170), topoisomerase II (Topo-II), glutathione S-transferase-pi (GST-pi), metallothionein (MT), heat shock protein-70 (HSP-70) and the putative regulators of resistance (ErbB1, Fos and Jun). Protein expression of Topo-II, GST-pi, MT, HSP-70, ErbB1, Fos and Jun was elevated in tumor tissue in comparison to normal tissue. The different expression of the proteins between tumoral and normal tissues was statistically significant for Topo-II (P = 0.05), MT (P = 0.03), and HSP-70 (P = 0.01), whereas ErbB1 showed a borderline significance. The expression of the proteins was frequently increased in smokers in comparison to non-smokers. In general, the increase of the proteins of smokers corresponded in tumoral and non-tumoral tissue. Different expression was only found with MT and HSP-70 which were higher in tissues of smokers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗