Epirubicin in patients with inoperable non-small cell lung cancer--a phase II study.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
K Mattson
Publications and source records attributed to K Mattson.
Recombinant interferon gamma treatment in non-small cell lung cancer. Antitumour effect and cardiotoxicity.
Fifteen patients with previously untreated, inoperable non-small cell lung cancer were treated with r-IFN-gamma 2 mg/m2, on alternate days three times a week for a maximum of 12 weeks. After IFN treatment patients with stage III a + b disease received radiotherapy (55 Gy/44 F/32 d b.i.d.), and 4/5 patients with stage IV disease received chemotherapy (cisplatin-vindesine). Ten patients were evaluable for response at 4 weeks; 9 had stable disease and one had progressive disease. At 12 weeks 7 patients were evaluable; one had a partial response, and 6 had stable disease. Of 10 patients subsequently given radiotherapy 2 achieved CR, 5 PR, and 3 SD. Of the 3 evaluable patients receiving chemotherapy 1 PR, 1 SD and 1 PD were observed. IFN-gamma treatment was discontinued due to toxicity in 7/15 of patients. Main toxicities were the 'flu'-like syndrome (in 15 patients) and cardiovascular events (in 13 patients). Three patients were withdrawn because of cardiotoxicity. Our results suggest that high dose r-IFN-gamma might have some biological activity in NSCLC and does not interfere with subsequent conventional therapies given with a curative intent.
Carcinoma, Non-Small-Cell Lung↗
Relative risk of mesothelioma associated with different levels of exposure to asbestos.
The relative risk of mesothelioma associated with different levels of exposure to asbestos was evaluated. The exposure was assessed from work histories of 51 mesothelioma cases and 51 sarcoidosis referents. The lung fiber concentration of the mesothelioma patients was compared with that of two reference groups (13 random autopsy cases and 43 male lung cancer patients). When the categories definite and probable were used as an estimated probability of occupational exposure, an odds ratio of 17.7 [90% confidence interval (90% CI) 3.4-253] and 3.0 (90% CI 0.9-10.6), respectively, was obtained. A lung fiber concentration of greater than 1 million fibers/g of dry tissue as an indicator of accumulated exposure gave an odds ratio of 14.4 (90% CI 2.5-178) for the men in comparison with the autopsy cases and 3.1 (90% CI, 1.3-7.5) in comparison with the lung cancer patients. Elevated risk of mesothelioma was shown to be associated with a lung fiber concentration of greater than 1 million fibers/g of dry tissue.
Adult↗
Correlations between findings at computed tomography (CT) and at thoracoscopy/thoracotomy/autopsy in pleural mesothelioma.
Thirty five computed tomography (CT) scans of the thorax and upper abdomen of thirty three patients with malignant pleural mesothelioma were correlated with the findings at thoracotomy (28 patients), thoracoscopy (2 patients) or autopsy (5 patients). Pleural thickening with contrast medium enhancement was detected on the CT scans of all patients. This finding was a valuable diagnostic tool, especially in cases of large amounts of pleural effusion and/or only thin layers of tumour barely or not at all visible on plain film chest X-rays. Difficulties in defining the exact extent of the diseases for clinical staging and/or evaluation of treatment response arose at the following sites: diaphragmatic pleura, chest wall, pericardium, mediastinum and mediastinal lymph nodes. Extension into the lung was difficult to identify following chemo- and/or radiotherapy. Our results show that CT is essential in the clinical management of mesothelioma. We recommend that CT scans of the chest and upper abdomen, using contrast medium enhancement, should be required in routine practice and in particular in clinical trials involving pleural mesothelioma.
Adult↗
Radiographic chest assessment of lung injury following hemithorax irradiation for pleural mesothelioma.
To characterize the nature, extent and time-course of radiation-induced lung injury, and to evaluate the usefulness of serial chest radiographs in this assessment, we studied 253 chest radiographs of 46 patients with pleural mesothelioma given hemithorax irradiation according to one of four different regimens: I 20 Gy; II 55 Gy; III hyperfractionation 70 Gy; IV hyperfractionation 35 Gy followed by local hypofractionation 36 Gy. Lung injury on the chest radiograph was graded from 0 (none) to V (maximal) based on the degree of loss of aerated lung tissue. Grade I changes were present 1-2 mths after radiotherapy in regimens II-IV. Grade V injury had developed in all but 3 out of 4 patients of the 20 Gy group by 6-12 months after irradiation. The extent and time-course of radiation-induced lung injury could be defined by serial chest radiographs alone. However, the documentation of tumour status and/or infections needed additional imaging or laboratory investigation, especially when grade IV-V lung injury was present. For research protocols evaluating radiation-induced lung injury serial chest X-rays are recommended at the following time-points: before treatment and 2, 6 and 12 mths after treatment, with additional computerized tomographic (CT) scans as required for differential diagnosis.
Female↗
Different imaging methods in the assessment of radiation-induced lung injury following hemithorax irradiation for pleural mesothelioma.
We have characterized the radiation-induced lung injury on serial chest X-rays, CTs and ultralow field MRs and evaluated the clinical value and cost/benefit ratio of the different imaging methods in 30 patients receiving high-dose hemithorax irradiation for pleural mesothelioma. Lung injury was severe in all patients, but non-specific and essentially as described in text-books. CT provided no clinically relevant, cost effective diagnostic advantage over conventional X-rays in the detection of early or late radiation-induced lung injury, but it was necessary for the evaluation of the disease status of mesothelioma. The possible advantage of MR over CT could not be evaluated and needs further studies. Optimal time-points for imaging CTs or MRs to detect early radiation-induced lung injury following high dose hemithorax irradiation were during the latter part of treatment or very shortly after the end of irradiation. Late injury or irreversible fibrosis developed rapidly after 6 months and was clearly documented by chest X-rays. We recommend serial chest X-rays at 1-2, 6 and 12 months following radiotherapy as a cost-effective method for the detection of radiation-induced lung injury with additional CTs to document the stage of mesothelioma, when needed.
Antineoplastic Combined Chemotherapy Protocols↗
Phase II study of trimetrexate and cyclophosphamide in previously untreated patients with inoperable non-small cell lung cancer.
Explore the source record for details and available documents.
Adult↗
Effect of inhaled natural interferon-alpha on diffuse bronchioalveolar carcinoma.
Six patients with diffuse bronchioalveolar carcinoma confined to the thorax were treated with interferon-alpha by inhalation. The dose was 1 or 6 MU thrice daily. Therapy was continued until the tumour progressed or bronchial hyperreactivity became unacceptable. The treatment was not effective.
Adenocarcinoma, Bronchiolo-Alveolar↗
Asbestos-related malignant mesothelioma: growth, cytology, tumorigenicity and consistent chromosome findings in cell lines from five patients.
Seven mesothelioma cell lines were established from clinical specimens from five patients with asbestos-related malignant pleural mesothelioma. The cells in culture show either epithelial or mixed epithelial/fibrosarcomatous growth with an average doubling time of 30 h. Giant multinucleated cells are common in all the cell lines, as well as long thin microvilli on the cell surfaces. All cell lines were cytokeratin positive and they stained negatively for monocyte-macrophage markers. All seven cell lines and one long-term tissue culture from a sixth mesothelioma patient were characterized cytogenetically. Karyotype analyses revealed complex structural and numerical abnormalities, primarily involving chromosome 1, 4, 5, 6, 7, 8, 9, 11, 12, 13 and 22. An excess of chromosome material of the short arm of chromosome 5 was seen consistently in six cell lines and in the long-term culture. In cell lines from four patients, changes in chromosome 13, mainly monosomy 13, were observed. The marker chromosomes observed in the early passages were conserved and few additional changes appeared in later passages. Six of the cell lines tested for tumorigenicity in athymic nude mice were weakly positive.
Adult↗
The clinical effect of medroxyprogesterone (MPA) in elderly patients with lung cancer.
Eighty-nine patients over 70 years old with untreated lung cancer, of various cell type and in various stages, were randomly assigned to chemotherapy (CT) alone or CT combined with medroxyprogesterone acetate (MPA). CT consisted of cisplatin, 60 mg/m2 i.v., along with etoposide (VP-16), 150 mg/m2 i.v., on day 1. The VP-16 was increased to 200 mg/m2, orally, on day 3. The entire regimen was given every 4 weeks for a maximum of six cycles. MPA was administered in daily 500-mg doses, i.m., 5 days a week for 1 month, followed by 1000 mg i.m., once a week, for 5 months. Changes in body weight and appetite were documented. After two cycles of CT, 64 patients were found to be evaluable for response. Forty-five had non-small-cell lung cancer (NSCLC) and 19 had small-cell lung cancer (SCLC). Thirty-seven patients had received CT alone and 27 CT plus MPA. In NSCLC, the objective response to CT alone was 36% versus 37% with CT plus MPA. In SCLC, the corresponding figures were 63% and 22%. The overall objective response rate was 60% in NSCLC and 48% in SCLC. Median survival using CT alone was 10 months for NSCLC patients and 11 months for SCLC patients. Using CT plus MPA, it was 10 months for NSCLC patients and 7 months for SCLC patients. In the control arm, 1-year survival was 42% for NSCLC patients and 48% for SCLC patients; in those who were given MPA, it was 48% for NSCLC patients and 9% for SCLC patients. Improved appetite and weight gain were reported more frequently by MPA patients, and they did not complain of CT's usual side effects. The fact that MPA had no significant effect on CT response or survival in patients also treated with a combination of cisplatin and VP-16, along with the small survival advantage for the control group in SCLC patients, suggests that combining MPA and CT may result in improved quality of life.
Aged↗
Changes in surfactant in bronchoalveolar lavage fluid after hemithorax irradiation in patients with mesothelioma.
Experimental studies have shown that the surfactant system of the lung is affected shortly after irradiation. It is unclear, however, whether surfactant plays a role in the pathogenesis of radiation pneumonitis. In the present study surfactant components (saturated phosphatidylcholine, surfactant protein A, phosphatidylglycerol, and phosphatidylinositol) and other phospholipids of bronchoalveolar lavage fluid (BAL) were studied in four patients with pleural mesothelioma before and during hemithorax irradiation (70 Gy) as well as zero, 1, 2, 3, and 4 months following irradiation. The concentrations of these same components and of soluble proteins were also estimated in the epithelial lining fluid (ELF) using urea as a marker of dilution. After radiotherapy, the concentrations of the surfactant components in ELF decreased to 12 to 55% of the control values before radiation, whereas the concentration of sphingomyelin in ELF increased ninefold. There were small changes in the other phospholipids. The concentration of soluble protein in ELF increased sevenfold. The minimum surface activity of crude BAL increased from 12 +/- 4 to 32 +/- 6 mN/m, and that of the sediment fraction of BAL increased from 7 +/- 4 to 22 +/- 6 mN/m, p less than 0.001. The protein-rich supernatant fraction of BAL from irradiated lung had a inhibitory effect on normal surfactant. There were significant correlations between the increasing severity of the radiologic changes on the one hand and, on the other, the saturated phosphatidylcholine/sphingomyelin ratio (p less than 0.001), the concentrations of soluble protein (p less than 0.001), and the concentrations of the surfactant components (p less than 0.02-0.001) in ELF.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Natural interferon-alpha alone and in combination with conventional therapies in non-small cell lung cancer. A pilot study.
Fourteen previously untreated patients with non-small cell lung cancer (NSCLC) were treated with natural interferon-alpha (IFN) in combination with conventional therapies. The planned dose of IFN was 6 x 10(6) IU/d.i.m. 5 days a week for 12 weeks. After 12 weeks of IFN monotherapy patients with M0 disease underwent twice-daily fractionated radiotherapy (RT), 55 Gy/4F/30 d, while IFN continued. Patients with M1 disease received 3 cycles of chemotherapy (CT) concomittantly with IFN. CT consisted of cisplatinum (P) 90 mg/m2 i.v. on days 1, 28, and 56 and of vindesine (VDS) 3 mg/m2 i.v. once a week 5 times and every other week thereafter for up to 8 courses. Thirteen patients were evaluable for response and toxicity. There were 9 patients with epidermoid, 3 with adeno- and one with large cell carcinoma. In 12 of 13 patients, the disease remained stable for 1 month during IFN monotherapy and one acheived a minimal response, which lasted 4 weeks. Of seven patients who completed the 12-week course of IFN monotherapy, 4 achieved stable disease (SD) and 3 had progressive disease. Three patients received RT and one received CT in combination with IFN as their subsequent treatment. There were 3 partial responses (2/3 after RT + IFN, 1/1 after CT + IFN), and 1 SD. Fatigue and weight loss were the most severe side-effects during IFN monotherapy. The combination of IFNs with conventional therapies might be clinically useful. We recommend further testing in larger studies.
Aged↗
A comparison of cis-platinum-vindesine and cis-platinum-etoposide combined with radiotherapy for previously untreated localized inoperable non-small cell lung cancer.
Seventy-two previously untreated patients with localized inoperable non-small cell lung cancer were randomized to a study comparing the efficacy of cis-platinum-vindesine (P-VDS) and of cis-platinum-VP16 (P-VP16), both combined with split-course radiotherapy. Fifty-nine patients were evaluable for response after the minimum requirement of two chemotherapy cycles. Both arms were further randomized to two split intervals, 3 or 5 weeks. The response rate to chemotherapy only (three cycles) was 66% for P-VDS and 50% for P-VP16. Radiotherapy increased the response rates to 83 and 67%, respectively. A Karnofsky score of 80% or more and the 3-week split interval were significant positive prognostic factors. Of all patients, 66% had local or combined recurrences and 17% relapsed at a distant site only. Since the 2-year survival rates are not strikingly better than those obtained by radiotherapy alone, we feel that these regimens should be restricted to further investigations of the role of chemotherapy in the treatment of different clinical presentations of NSCLC.
Aged↗
Chromosomal abnormalities and their correlations with asbestos exposure and survival in patients with mesothelioma.
Cytogenetic findings of our 30 previously reported and eight new patients with malignant pleural mesothelioma were summarised and correlated with asbestos fibre burden in lung tissue and survival. Successful cytogenetic analyses were performed on cells obtained from the tumours and/or pleural effusions of 34 of the 38 patients. Clonal chromosomal abnormalities were detected in 25 patients, 19 of them studied before treatment. Nine patients, seven of them studied before treatment, had normal karyotypes and/or non-clonal chromosomal abnormalities. Most of the karyotypic findings in the patients with clonal abnormalities were complex and heterogeneous, and no chromosome aberration specific to mesothelioma could be demonstrated. The following numerical abnormalities in decreasing order of frequency were preferentially present in karyotypic changes: -22, +7, -1, -3, -9, +11 and -14 (-/+ denoting partial or total loss or gain). Translocations and deletions involving a breakpoint at 1p11-p22 were the most frequent structural aberrations. Statistically significant correlations were found between high content of asbestos fibres in lung tissue and partial or total losses of chromosomes 1 and 4, and a breakpoint at 1p11-p22 (P = 0.0001, P = 0.003, P = 0.009, respectively). The number of copies of chromosome 7 short arms was inversely correlated with survival (P = 0.02). In this study no diagnostic cytogenetic markers of mesothelioma were found, instead the copy number of chromosome 7 short arms turned out to be a possible prognostic factor in malignant mesothelioma.
Adult↗
Pharmacokinetics and toxicity of inhaled human interferon-alpha in patients with lung cancer.
Eight patients with advanced, previously treated non-small cell lung cancer inhaled natural leukocyte interferon-alpha (IFN-alpha) from a dosimeter-equipped jet nebulizer. Single doses of IFN ranged from 1 x 10(6) to 120 x 10(6) IU. Serum IFN was undetectable after single doses of 1 x 10(6) to 18 x 10(6) IU, but 60 x 10(6) IU resulted in measurable levels of circulating IFN in 3 out of 6 patients. All 5 patients who inhaled 120 x 10(6) IU had between 11 and 35 IU of IFN per milliliter of serum for at least 12 h. No systemic or local side effects were observed after 1 x 10(6) to 18 x 10(6) IU, but doses of 60 x 10(6) to 120 x 10(6) IU resulted in temperature rise, headache, and malaise. All symptoms started within 3-6 h, reached their peak by 8-10 h, and lasted until 12-24 h after inhalation. A decrease (greater than 20%) in peak expiratory flow following inhalation was temporarily found in 2 patients. We conclude that IFN, given by inhalation, penetrates into the blood stream, thus causing systemic side effects similar to those described after systemic IFN administration and, in addition, occasionally reversible airflow obstruction.
Administration, Inhalation↗
Bronchial carcinoid with a twenty-four-year natural history. A case report.
Explore the source record for details and available documents.
Bronchial Neoplasms↗
Nonrandom chromosomal abnormalities in malignant pleural mesothelioma.
Cytogenetic studies were performed on tumor cells from specimens of 30 consecutive patients with malignant pleural mesothelioma. Metaphases for chromosomal G-banding analyses were obtained from 27 of these patients. Clonal abnormalities were detected in 19 patients. Karyotype findings were complex and heterogeneous: aneuploidy, polyploidy, structural abnormalities, and several subclones were seen. The most frequent chromosomal abnormalities were polysomy or partial polysomy 7, monosomy or partial monosomy 22, and rearrangements involving breakpoints at 1p11-22.
Adult↗
Pharmacokinetics of epirubicin in man. Non-influence of alpha interferon.
The influence of alpha interferon on the plasma pharmacokinetics of epirubicin has been studied in five patients with bronchial cancer. The pharmacokinetic studies of epirubicin (100 mg m-2) were performed prior to and immediately after a 3 wk period with daily natural alpha interferon treatment (6 x 10(6) IU i.m.). None of the patients had been treated with antracyclines or interferon prior to entering the present study. The plasma pharmacokinetics of epirubicin were most adequately described by a three compartment open model both prior to and after the interferon treatment. The interferon treatment had no influence on the pharmacokinetics of epirubicin (AUC, Cmax, terminal half life).
Aged↗