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R Stahel

Publications and source records attributed to R Stahel.

34 records · Page 2Linked to original sources
PubMed1995

Quality versus quantity of life in the treatment of patients with advanced small-cell lung cancer? A randomized phase III comparison of weekly carboplatin and teniposide versus cisplatin, adriamycin, etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: Based on a promising pilot study with weekly carboplatin and teniposide (CBDCA/VM) the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with extensive-disease small-cell lung cancer aimed at the development of an effective palliative treatment with low subjective toxicity. PATIENTS AND METHODS: From September 1989 to September 1991 patients were randomised to a weekly regimen of CBDCA/VM or to our 'standard chemotherapy' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine (PAV-CyMOC). RESULTS: The trial was closed before the planned accrual of 140 evaluable patients due to a significant survival difference shown by an interim analysis. Of the 61 patients 59 were eligible and included in the final analysis. The results achieved with the PAV-CyMOC regimen were significantly better than those observed in patients treated with weekly CBDCA/VM (remission rate of 65% vs. 29%; p = 0.006). The median survival of patients treated with the PAV-CyMOC combination was significantly longer than that of patients receiving weekly CBDCA/VM (260 days vs. 147 days; p = 0.0035). The 1-year survival rate was 30% in the PAV-CyMOC arm compared to 4% in the CBDCA/VM-treated patients. As expected, side effects including myelosuppression, alopecia and mucositis were significantly more pronounced in patients treated with the PAV-CyMOC regimen. No significant difference was found in patient-rated tumor symptoms and general quality-of-life categories. CONCLUSION: Contrary to our initial expectation that we would achieve similar therapeutic results with less subjective toxicity, in this randomised prospective trial the results achieved by weekly carboplatin and teniposide were significantly inferior in terms of remission rate and survival to those of our 'standard regimen' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. The weekly regimen was less toxic than the standard chemotherapy. Whether patients are willing to accept a significant trade-off between quantity and quality of life remains to be evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Early versus late alternating chemotherapy in small-cell lung cancer. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: From 1984 to 1989, the Swiss Group for Clinical Cancer Research (SAKK) performed a randomized phase III trial comparing early versus late alternating chemotherapy in patients with small-cell lung cancer. PATIENTS AND METHODS: 406 eligible patients were entered into the trial. Regimen A consisted of PAV (cisPlatin, Adriamycin, VP 16-213, and Regimen B of CyMOC (Cyclophosphamide, Methotrexate, Oncovin, CCNU). Cycles were repeated as rapidly as possible. patients were randomized to receive either ABABAB (early alternating chemotherapy) or AAABBB (late alternating chemotherapy). After six cycles patients with limited disease in complete or partial remission and those with extensive disease in complete remission received irradiation to the primary (45 Gy) and the CNS (36 Gy). RESULTS: The overall remission rate was 87% with 31% complete remissions. The median survival of all 406 eligible patients was 346 days with 15% of the patients alive at two years. The overall remission rate, the rate of complete remission, the median survival and the rate of long-term survival were not significantly different in the two treatment arms. In limited disease the estimated percentages of survival at 2 years were 33% in the early and 24% in the late alternating chemotherapy arms. Patients with extensive disease survived significantly longer with late alternating chemotherapy than on the early alternation regimen (median survival 336 days versus 301 days, p = 0.01). In the latter patients the received dose intensities (RDI) of cisplatin, adriamycin and etoposide were significantly higher in the late-alternation arm. Patients treated with early alternating chemotherapy rated their tumor symptoms, functional states, fatigue/malaise and restriction of social activity significantly better, reflecting an improved subjective adjustment. CONCLUSIONS: Alternating chemotherapy with PAV-CyMOC plus consolidating radiotherapy is a feasible and effective treatment for small-cell lung cancer, with acceptable toxicity. Whereas patients with early alternating chemotherapy achieve a better subjective adjustment, late alternating chemotherapy allows for a higher RDI of cisplatin, adriamycin and etoposide, which results in a significantly longer median survival of patients with extensive disease.

Actuarial Analysis↗
PubMed1994

[Diffuse thymus hyperplasia following chemotherapy for nodular sclerosing Hodgkin lymphoma].

A persistent or new mass in the anterior mediastinum after chemotherapy for mediastinal lymphoma poses a major differential diagnostic problem. Misinterpretation as a persistent or recurrent tumor may lead to additional unnecessary and potentially harmful therapy. Benign mediastinal tumors, albeit very rare, need confirmation by biopsy since they cannot be distinguished by radiological methods from persistence or relapse of lymphoma. We present a case report of a patient with diffuse thymic hyperplasia following successful chemotherapy for nodular sclerosing Hodgkin's disease, with a review of the literature.

Adult↗
PubMed1994

Weekly carboplatin and VM-26 for elderly patients with small-cell lung cancer.

BACKGROUND: Elderly patients are excluded from chemotherapy trials, even though they represent 25% of those with small cell lung cancer. An effective chemotherapy regimen with limited toxicity should be developed with the aim not only of increasing the survival of these patients, but also of improving their quality of life and their independence. PATIENTS AND METHODS: Twenty-four patients with a median age of 72 years and small-cell lung cancer (SCLC) were included in the trial. Chemotherapy consisted of a weekly intravenous regimen of Carboplatin 80 mg/m2 and Teniposide 80 mg/m2 administered on an outpatient basis. RESULTS: Eight patients had limited and 16 extensive disease. After a median of 12 chemotherapy courses (2-31) the overall response rate was 66.7% (95% Cl: 44.7-84.4), with 5 patients in complete and 11 in partial remission. The median overall survival was 33 weeks, with 4 patients alive at more than one year. Improvement of symptoms occurred in 86% of patients. Toxicity, mainly hematological, was moderate. CONCLUSIONS: Weekly Carboplatin and VM-26 is an effective and non-toxic regimen for elderly patients, leading to results similar to those obtained with a more intensive regimen in a younger age group.

Aged↗
PubMed1994

Autoantibodies in neurological paraneoplastic diseases.

Paraneoplastic syndromes such as the subacute sensory neuronopathy (SSN) and paraneoplastic cerebellar degeneration (PCD) are associated with autoantibodies directed against various neural antigenic structures. SSN is characterised by autoantibodies against a neuronal intranuclear component called Hu (M. W. 35 to 40 kD), whereas in PCD these antibodies are directed against a Purkinje cell cytoplasmic component called (M. W. 34 and 65 kD). Neuroblastoma cell lines maintained in culture have been shown to contain neuronal antigens. We have demonstrated the presence of the Hu antigen in neuroblastoma cell lines such as SKN-SH, LAN-1 and IMR-32 by both immunocytochemistry and immunoblots of nuclear extracts. The Yo paraneoplastic antigen has been found to be expressed in HeLa cells. These methods may be used for screening of patients with suspected paraneoplastic disease and/or malignancy. Western blot analysis appears to be superior to immunohistochemistry alone. In our experience only 11 out of 122 SCLC patients were positive for the anti-Hu antibody, whereas 5 out of 5 patients with SSN/SCLC were positive, and all of the neurological controls were negative. The availability of cell lines expressing paraneoplastic antigens offers an easy diagnostic assay which may complement or replace conventional immunohistochemistry.

Autoantibodies↗
PubMed1992

Human small cell lung cancer expresses the octamer DNA-binding and nervous system-specific transcription factor N-Oct 3 (brain-2).

Small cell lung cancer (SCLC) cells express several characteristics of neuronal cells, including synthesis of neuropeptides and expression of the respective receptors. Establishment and maintenance of the neuronal phenotype of SCLC may depend on expression of gene transcription factors inherent to the central nervous system. The present study shows the nervous system-specific transcription factor N-Oct 3 (brain-2) to be expressed in all 13 SCLC cell lines investigated. Furthermore, N-Oct 3 (brain-2) was also found in SCLC-derived skin metastasis. In contrast, in extracts and RNA of non-SCLC cell lines and non-SCLC tumor tissues, such as lung squamous, large cell, and adenocarcinoma, expression of N-Oct 3 (brain-2) was not detectable. These data support the concept that SCLC cells derive from the neuroectodermal cell lineage since expression of N-Oct 3 (brain-2) protein is highly abundant at the neural tube stage and in the adult restricted to the neuroectodermal cell lineage.

Carcinoma, Small Cell↗
PubMed1991

Allelic loss on the short arm of chromosome 11 in non-small-cell lung cancer.

Forty-eight samples of primary non-small-cell lung cancer (NSCLC) and normal tissue from the same patients were analyzed for allelic deletions on chromosome 11p. Five polymorphic loci were assessed to determine the incidence of 11p sequence deletions and to define hot-spots of deletions. Information was obtained from all patients in at least one locus. Our data show that the deletions observed were not randomly scattered over the short arm of chromosome 11. Rather, 2 hot-spots of deletions were observed: one in the area of the genes for catalase and beta-FSH corresponding to band 11p13, the other close to the IGF-II locus corresponding to band 11p15. A high incidence of loss of heterozygosity (LOH) was found with the probe for catalase (21/29), a locus flanking the centromeric region of the Wilms' tumor locus. Most of the samples exhibiting LOH of one or more of the alleles analyzed remained heterozygous for at least one other chromosome 11p allele. Furthermore, duplication of the intensity of the remaining allele was rarely observed. Our results indicate that LOH on the short arm of chromosome 11 is a common event in NSCLC and that the chromosomal region containing the Wilms' tumor locus is most commonly involved.

Alleles↗
PubMed1990

Combination chemotherapy with mitomycin, vindesine, and cisplatin for non-small cell lung cancer. Association of antitumor activity with initial tumor burden and treatment center.

From 1984 through 1986, 205 patients with non-small cell lung cancer were entered into a group-wide trial of the Swiss Group for Clinical Cancer Research (SAKK). This trial evaluated the combination of mitomycin (8 mg/m2 intravenously [IV] on day 1), vindesine (3 mg/m2 IV on days 1 and 8), and cisplatin (60 mg/m2 IV on day 1) with forced diuresis, repeated every 4 weeks (MiViP regimen). One hundred eighty-three patients were evaluable. Six complete and 69 partial responses were documented for an overall response rate of 41% (95% confidence interval, 34% to 50%). In the multivariate analysis the strongest predictors for response were the participating institution and the number of initially involved organ sites. The estimated median time to progression for patients with a complete response, partial response, or stable disease was 155 days (estimated inter-quartile range, 99 to 258 days). In the multivariate analysis the time to progression was significantly associated with the number of involved organ sites (P = 0.041). The estimated median survival time for the 183 evaluable patients was 239 days (estimated inter-quartile range, 137 to 436 days). In univariate and multivariate analyses performance status, number of involved organ sites, pretreatment status with radiation therapy, and participating institution were all significantly associated with survival. The principal toxicities were myelosuppression and nausea and vomiting with 16% of the patients refusing further treatment after a median of four cycles of chemotherapy. In conclusion, the MiViP regimen was an active combination chemotherapy in patients with non-small cell lung cancer in a large trial performed by the SAKK. The prognostic value of the participating institution and the number of organ sites involved by metastatic deposits in non-small cell lung cancer needs further investigation.

Adult↗
PubMed1990

Morphologic analysis of human lymphokine-activated killer (LAK) cells.

Lymphokine-activated killer (LAK) cells obtained from normal donors at various days of in vitro cultivation have been studied by several methods including scanning (SEM) and transmission (TEM) electron microscopy, immuno-electron microscopy, in situ hybridization and flow cytometric DNA measurements. In addition, the cytotoxic activity of LAK cells against several tumor cells was examined by 51Cr-release assay and by SEM and TEM. The LAK cells displayed a uniform ultrastructural appearance concerning surface structure and morphology of organelles. They contained typical lysosomal granules which by immuno-electron microscopy showed a specific localization of perforin I (PI). The presence of PI and granzymeA mRNA in the cytoplasm was confirmed by in situ hybridization using specific antisense probes. Frequency and increased of specific mRNA-containing cells was similar for both genes. Single LAK cells were further characterized by peculiar nuclear inclusion bodies (IB) which were presumably formed by trapped profiles of endoplasmic reticulum. Flow cytometric analysis revealed normal DNA content of LAK cells even after prolonged cultivation indicating that the IB were not associated with aneuploidy of the effector cells. The LAK cells were highly effective in lysing K562 and DAUDI cells as shown by 51Cr-release assay. They caused characteristic morphologic alterations of target cells similar to those found in cytotoxic T-lymphocyte (CTL) and NK-cell-mediated cytolysis. SEM and TEM studies on specimens prepared by routine procedures or by cryopreparation showed that the tumor cell membrane was the initial target for the LAK cell attack whereas other cell compartments were damaged only in advanced stages of cytolysis. Summarizing our study demonstrates that LAK cells have a characteristic ultrastructure which in some aspects differs from that of CTL and NK cells, and that LAK cells appear to destroy tumor cells by mechanisms similar to those of other cytotoxic effector cells.

Cell Nucleus↗
PubMed1990

[5 and 10 years results of surgical treatment of lung metastases].

This is a report on 105 patients who had 125 thoracotomies for 188 lung metastases between 1960 and 1987. The cumulative survival rate at 5 years was 39% and 24% at 10 years and 13% at 15 years. The median survival is 3.7 years, the average survival is 7 years due to prolonged follow-up. With combined modality therapy, testicular and uterine cancers yielded the best survival results with a 5-year survival rate of 100% and 67%, respectively. In multi-variate analysis, response to prior chemotherapy, local tumor extent (intrapulmonary versus extrapulmonary disease) and venous drainage (caval type versus portal type) were the most important prognostic factors whereas the number of metastases and the interval between primary tumor and lung metastases were of minor prognostic importance. The present results are compared with long-term results of other centres and emphasize the importance of resection in combined modality therapy concepts of lung metastases.

Adolescent↗
PubMed1988

Membrane antigens of human bronchial epithelial cells identified by monoclonal antibodies.

Subpopulations of normal bronchial epithelial cells were identified using a series of murine monoclonal antibodies. These antibodies were used to stain intact bronchial epithelial cells in culture by indirect immunofluorescence. LAM 2 reacted with 80%, LAM 6 with 75%, LAM 7 with 60%, and LAM 8 with 5% of these cells. Sections of human bronchial epithelium were also stained with these antibodies by immunoperoxidase methods. LAM 2 was found to bind with 80%, LAM 6 with 65%, LAM 7 with 50%, and LAM 8 with less than 1% of bronchial epithelial cells. LAM 2 stained both columnar epithelial cells and basal cells; LAM 6 stained mainly basal cells and only a small proportion of columnar cells; LAM 7 showed specificity for basal cells; LAM 8 distinctly stained single cells in the basal cell layer. These antibodies were previously shown to react with the surface membrane of human lung carcinomas, ranging from the broad reactivity of LAM 2 with small cell and non-small cell lung cancers to the highly restricted reactivity of LAM 8 with small cell carcinomas of the lung. Thus, membrane antigens have been identified in bronchial epithelial cells by monoclonal antibodies which exhibit a similar range of cellular reactivity in vitro as in vivo. Inasmuch as these antibodies recognize subsets of cells which could not be easily distinguished by morphologic characteristics, these reagents may be useful in classifying bronchial epithelial cells.

Antibodies, Monoclonal↗
PubMed1986

Chromosome changes in malignant mesothelioma.

Cytogenetic study was made of mesothelioma cells from 14 patients. Metaphases were obtained from 12 tumors and revealed aneuploidy and clonal abnormalities in 9 specimens. In the two remaining cases, no metaphases were obtained. The cytogenetic abnormalities were complex, and up to 12 marker chromosomes were observed in the tumors. Rearrangements of chromosomes #1, #2, #3, #6, #9, #11, #17, and #22 were most frequently observed. Chromosome markers involved diverse bands, including several that are loci of oncogenes, fragile sites, and nonrandom rearrangements in other types of cancer. This study shows that the karyotypes of malignant mesothelioma can be analyzed by standard cytogenetic techniques. Additional studies of untreated mesothelioma may help to distinguish primary cytogenetic changes from effects of prior therapy in some of our patients.

Adult↗
PubMed1983

[Spontaneous radial segmentation of cell nuclei: morphologic marker of T-cell neoplasms?].

Radial segmentation (RS) of leukocyte nuclei has been observed, for example, in leukemias (Rieder cells). In 6 of 8 patients with T-ALL, RS of neoplastic cells was found in the peripheral blood, whereas in 14 patients with non-T-ALL no RS cells were present. RS may be a morphologic marker for certain T-cell neoplasms, and with regard to ultrastructure it seems to be identical to heat-induced RS of non-neoplastic cells.

Cell Nucleus↗
PubMed1983

Radial segmentation of nuclei (Rieder cells): a morphological marker of T-cell neoplasms?

Pretreatment blood smears of adult patients with acute lymphoblastic leukemia were examined for neoplastic cells showing nuclear radial segmentation (RS). RS was present in 6 of 7 patients with immunologically proven T-cell leukemia, but not in 11 patients whose leukemic cells lacked T-cell markers. Electron microscopic studies of neoplastic cells showed multiple nuclear indentations and abundant cytoplasmic microfilaments and microtubuli in connection with pericentriolar dense material. RS formation was decreased in 1 patient after chemotherapy with a vincristine-containing regimen, while the white cell count remained unchanged. Radial segmentation (RS) of leukocyte nuclei is a well-known phenomenon, which is observed ex vivo (Rieder cells), and can be induced in vitro. Convoluted or multilobulated nuclei in lymphoid neoplasms are similar to RS nuclei both with regard to their structure and their sensitivity to spindle-blocking drugs. We propose that the nuclear alterations observed in a variety of different T-cell neoplasms are identical with RS, and suggest that RS might be a morphological marker for subsets of lymphoproliferative disorders of T-cell origin.

Adult↗