Efficacy of a toxicity-adjusted topotecan therapy in recurrent small cell lung cancer.

The present prospective multicentre trial investigated whether topotecan, given at a starting dose of 1.25 mg.m(-2) with individual dose adjustment, can improve safety in patients with relapsed/refractory small cell lung cancer without loss of efficacy. Patients received topotecan intravenously on days 1-5, every 21 days, for up to six courses. In the absence of relevant haematotoxicities, topotecan was increased to 1.5 mg.m(-2) and reduced to 1.0 mg.m(-2) in case of severe haematotoxicities. Of 170 recruited patients, 73.2% had stage IV disease and 63.4% had platinum-containing pre-treatment. Patients received a total of 521 courses. In 72.6% of those courses, the dose remained at 1.25 mg.m(-2); in 9.1% it was reduced and in 18.3% it increased. Overall response rate was 14.1% including one complete response; 28.8% had stable disease. Median duration of response was 13.6 weeks and median survival was 23.4 weeks. Clinical benefit was obvious for sensitive as well as for refractory patients. Haematotoxicity of grade 3 or 4 was clearly lower compared with the standard dose of 1.5 mg.m(-2). In conclusion, topotecan at a dose of 1.25 mg.m(-2) appears to be as effective as the dose of 1.5 mg.m(-2), but with reduced toxicity. Since patients with recurrent small cell lung cancer have a poor prognosis, they benefit especially from good tolerability.

[Matrix metalloproteinases and their inhibitors in lung cancer with malignant pleural effusion]. / Matrix-Metalloproteinasen und deren Inhibitoren bei Lungenkarzinomen mit malignem Pleuraerguss.

UNLABELLED: Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) play a crucial role in physiological and pathological matrix turnover. This study aimed to determine the occurrence of MMP and TIMP in lung cancer patients with malignant pleural effusions (CA). METHODS: MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1, and IMP-2 oncentrations were determined by ELISA and zymography in pleural effusions and plasma of 31 CA and 14 congestive heart failure (CHF) patients and in plasma of 18 healthy controls (CON). RESULTS: MMP-2, TIMP-1, and TIMP-2 ELISA-concentrations were increased in CA pleural fluid vs. CA plasma (p < 0.005, p < 0.005, p < 0.05), in contrast to MMP-9 being higher in plasma (p < 0.005). Pleural fluid MMP-1 and MMP-8 were increased in CA vs. CHF (p < 0.05, p < 0.005). MMP and TIMP plasma concentrations were not different in CA vs. CHF, but MMP-9, TIMP-1, and TIMP-2 were increased vs. CON (p < 0.005, each). Gelatine zymography MMP-9/MMP-2 ratios were increased in CA plasma vs. effusion fluid (p < 0.005), in CA vs. CHF plasma, CA vs. CHF effusions (p < 0.005 each), and in CA vs. CON plasma (p < 0.05). CONCLUSIONS: MMP-2, TIMP-1, and TIMP-2 accumulate in the pleural compartment in CA and CHF, probably reflecting an unspecific pleural reaction. MMP-1 and MMP-8 are increased in cellular rich CA pleural effusions only. The determination of MMP-9/MMP-2 ratios in pleural fluid may contribute to differentiate CHF from CA effusions.

Vascular endothelial growth factor in pleural effusions of different origin.

This study aimed to determine the diagnostic relevance of vascular endothelial growth factor (VEGF) in the pleural fluid and serum of patients with pleural effusions of different aetiology. VEGF was quantified in the pleural effusion fluid and serum of 96 patients with malignancies (58 lung cancers (CA) and 38 tumours with secondaries to the lung (TM)), 45 with congestive heart failure (CHF), 28 with tuberculosis (TB), 45 with acute infections (INF), and in the serum of 20 healthy controls. VEGF pleural effusion concentrations were significantly different in the main diagnostic groups. VEGF was higher in effusions of patients with malignancies (CA as well as TM) in comparison with INF, TB or CHF. In serum, however, high VEGF concentrations indicated CA, TM or INF, but not TB or CHF. Despite significant differences of VEGF levels in different patient groups, receiver-operating characteristic analysis revealed insufficient diagnostic value of VEGF for differential diagnosis of pleural effusions. In conclusion, vascular endothelial growth factor serum concentration is highly suggestive of the presence of lung disease in general, except for tuberculosis. In effusion fluid, the presence of vascular endothelial growth factor clearly indicates inflammatory or malignant origin. However, for diagnostic use, additional parameters besides vascular endothelial growth factor are mandatory.

[Patient with left-sided pleural effusion and large structures of soft-tissue-density in the mediastinum]. / Patient mit Pleuraerguss links und grossen weichteildichten Strukturen im Mediastinum. Pankreatitis mit Pleuritis und mediastinaler Beteiligung.

A patient was admitted to the hospital to clarifying a left-sided pleural effusion. Typical cytological findings in pleural effusion did not leave a doubt about being present a pancreatitis in conformity with clearly increased levels of lipase and amylase in the effusion fluid. The CT of the upper abdomen showed signs of a exsudative pancreatitis. In the chest CT as well as in transesophageal ultrasound evaluation large structures of soft-tissue-density together with areas of encapsulated fluid were seen in the dorsal mediastinum reaching down to the diaphragm and abdomen. Just with subsequent diet and strict termination of any alcohol consumption the pathological findings recovered completely. Due to the expansive involvement of the pleural, mediastinal and abdominal compartments this is an extraordinary case of acute pancreatitis.

[Fine needle aspiration cytology as diagnostic bed-side method for differential diagnostics of enlarged peripheral lymph nodes]. / Die Feinnadelaspirationszytologie als diagnostische bed-side-Methode zur differenzialdiagnostischen Abklärung peripherer Lymphknotenschwellungen.

Enlarged lymph nodes are a common diagnosis in clinical practice. The causes are varied and both benign or malignant processes might be responsible. Clearly it is important to quickly discern whether the origin is malignant or benign. The aim of this study was to evaluate the reliability and efficacy of aspiration cytology of enlarged lymph nodes. 398 patients with peripheral enlarged lymph nodes, who, in the course of a five-year period, were subjected to at least one immediate cytologic analysis (bed-side-analysis), were included in the study. For comparison the gold standard was defined as either the histological result of a corresponding biopsy or the clinical outcome within an observation period of one year. Cytology analysis reached a sensitivity of 97.6% and a specificity of 96.0% of all lymph nodes analysed. For metastatic lymph nodes of solid neoplasmas (mainly bronchial carcinoma) sensitivity was even 98.7% (90.6% for malignant lymphomas). In conclusion, fine needle lymph node aspiration cytology is a quick, reliable, technically simple method for further assessment of enlarged lymph nodes in order to distinguish between benign and malignant causes. Further differentiation of the underlying type of malignant origin can be achieved with high efficacy. Thus, in the hands of a qualified investigator, fine needle lymph node aspiration cytology is a suitable method for use on a bed-side basis.

Comparison of three tropisetron-containing antiemetic regimens in the prophylaxis of acute and delayed chemotherapy-induced emesis and nausea.

There is still controversy as to what constitutes the optimal therapy for acute and delayed chemotherapy-induced emesis and nausea. We conducted a three-armed randomized multi-centre study in 193 chemotherapy-naive patients receiving highly emetogenic chemotherapy inducing both acute and delayed symptoms (cisplatin > or = 50 mg/m2, carboplatin > or = 300 mg/m2, cyclophosphamide > or = 750 mg/m2, ifosfamide > or = 1.5 g/m2 on day 1). Group A: 1 x 5 mg tropisetron i.v. on day 1 + 2, then 10 mg p.o. (oral dose now recommended: 5 mg); group B: tropisetron as for A+dexamethasone, 20 mg i.v., on days 1 + 2, then 4 mg i.v./p.o.; group C: tropisetron as for A+metoclopramide, 20 mg i.v. +2 x 10 mg p.o. on day 1, then 3 x 10 mg p.o. Treatment was continued for at least 2 days after the end of chemotherapy. Tropisetron+dexamethasone was significantly superior to tropisetron alone both for acute (P = 0.0064) and delayed (P = 0.0053) emesis. Complete control of acute and delayed emesis (nausea) was achieved in 80% (75%) and 53% (46%) in group A, 97% (90%) and 80% (58%) in group B, and 86% (80%) and 49% (45%) in group C. Patients completely asymptomatic during the whole cycle accounted for 26% of those in group A, 49% in group B and 28% in group C. The most frequent adverse events were constipation (16.6%), headache (7.3%) and tiredness (7.3%). Once-daily tropisetron+dexamethasone over several days is well tolerated and is a simple means of achieving further significant improvement in the efficacy of tropisetron against acute and delayed symptoms.

Prevention of chemotherapy-induced nausea and vomiting by tropisetron (Navoban) alone or in combination with other antiemetic agents.

We report an open, three-armed, multicenter study being carried out to assess the optimum treatment for acute and delayed emesis and nausea in patients undergoing highly emetogenic chemotherapy. Eighty-seven patients were randomized to receive tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland), tropisetron plus dexamethasone, or tropisetron plus metoclopramide during chemotherapy. Tropisetron in combination with dexamethasone produced the best control of both acute and delayed emesis. Acute vomiting was prevented in 69% of patients by tropisetron monotherapy, and the addition of dexamethasone significantly increased the total control of vomiting to 92% (P < .01). Similarly for delayed vomiting, total control of emesis was seen in approximately 70% of patients on tropisetron alone during days 2 and 3; this control rate increased to almost 90% with combined tropisetron/ dexamethasone treatment. In all patients receiving cisplatin, the tropisetron/dexamethasone combination produced total control of acute emesis. The tropisetron and dexamethasone combination also provided the best control of acute and delayed nausea. Tropisetron produced total control of acute nausea in 69% of patients. The addition of dexamethasone increased this control rate to 81%. Similarly for delayed nausea, on days 2 and 3 of treatment, dexamethasone plus tropisetron provided total control of nausea in more than 80% of patients compared with a control rate of more than 60% achieved using tropisetron. The combination of tropisetron and metoclopramide did not improve significantly on the control of nausea and vomiting achieved using tropisetron alone. Evaluation of quality of life events by patients indicated no appreciable change in their mental or physical condition during chemotherapy, irrespective of antiemetic therapy. In the tropisetron and tropisetron plus metoclopramide treatment groups, a decreased food intake was observed due to delayed nausea while the addition of dexamethasone prevented loss of appetite. The antiemetic treatments were similarly well tolerated. The most common adverse events were constipation (15%) and tiredness (7%).

[Value of cytologic diagnosis of pulmonary carcinoid tumors. A morphologico-clinical analysis]. / Zur Wertigkeit der zytologischen Diagnostik von pulmonalen Karzinoidtumoren. Eine morphologisch-klinische Analyse.

14 centrally and 16 peripherally located carcinoid tumors of the lung were included in the study. For the centrally situated carcinoids the cytological interpretation of imprints or smears from the surface of the biopsy specimens turned out to be superior to the histological diagnosis based on the same endoscopic bronchial biopsy. 10 out of 12 cytologically investigated cases were correctly diagnosed. In the remaining 2 cases one was misdiagnosed as a small cell carcinoma and the other one raised suspicion of malignancy (Pap-III-finding), but no definitive diagnosis could be made. By contrast, out of 11 histologically investigated endoscopic biopsies from central carcinoids 5 were misdiagnosed as small cell carcinomas and in one case the material obtained endoscopically was inadequate. Out of the 16 peripheral carcinoid tumors only 5 were diagnosed cytologically: 3 by catheter aspiration and 2 by transthoracic needle biopsy. The characteristic cytologic feature of carcinoid tumors and the cytological differential diagnosis are described in detail.

[Results of the transthoracic fine needle biopsy]. / Ergebnisse der transthorakalen Feinnadelbiopsie.

The transthoracic fine needle biopsy is a very efficient method in the differential diagnosis of pathological intraplumonary or mediastinal processes. If the material is representative (out of 918 patients in 71.6 percent), the cytological examination produced a correct result in 93.4 percent (in 614 cases out of 658). In 428 cases of intrathoracic malignant diseases an accurate diagnosis was established in 94.6 percent, and out of the patients with a benign inflammatory disease we could give frequently a hint at the definitive diagnosis in addition with other clinical and paraclinical dates. The false positive rate was 1.3 percent, and in 5.3 percent a false negative result was obtained. Our rate of complications was 16.7 percent.

[Statement of the bioptic diagnostic in intrathoracic sarcoidosis--team work of 6 lung hospitals of the GDR (author's transl)]. / Stand der bioptischen Diagnostik bei intrathorakaler Sarkoidose--Erfahrungen von 6 Lungenkliniken der DDR.

A nearly nation-wide team-work of six chest hospitals was made with 4284 patients to analyse all performed diagnostic procedures up to the present. Its frequency and diagnostic importance in relation to the radiographic stages of the disease were examined. Especially the procedure of bronchologic examination, having been partly underrated with the morphological ascertainment of sarcoidosis, are now purposefully analysed. This showed that also with perbronchic punction-biopsy and bronchoscopic excision morphologically confirming of the diagnosis was possible at a high percentage. On the other side the right diagnosis was made clinically before bioptic procedures in the majority of the patients. The overall conclusion is that, according to the experiences made in our hospitals, the relatively harmless bronchologic procedures are in general sufficient to obtain bioptic verfication of the diagnosis "sarcoidosis". Other bioptic operations like mediastinoscopy or lung biopsy can be restricted to cases with reasonable doube of the diagnosis.