Time course of exhaled hydrogen peroxide and nitric oxide during chemotherapy.

This study was designed to assess the effect of differential leukocyte depletion during chemotherapy by monitoring the levels of exhaled hydrogen peroxide H2O2 and nitric oxide (F(eNO)) present. In 39 patients with lung cancer (chronic obstructive pulmonary disorder up to stage II, median forced expiratory volume in one second 78% predicted), measurements were performed before a cycle of therapy (day 1), at least once during the cycle (day 8: n = 34; day 15: n = 19), and afterwards (days 21-29). There were significant changes in the level of H2O2, F(eNO) and peripheral blood cell differentials over the visits. The level of H2O2 was decreased only on day 15, with a median (difference between the upper and lower quartiles) fall of 31 (57)%, while F(eNO) was reduced only on day 8, by 22 (40)%. Neutrophil numbers were unchanged on day 8 and decreased by 59 (48)% on day 15, while monocyte numbers were decreased on day 8 by 87 (39)%. On days 21-29, values had returned to baseline. Taken together with previous findings, the parallel course of levels of exhaled hydrogen peroxide and neutrophil counts suggests that a major part of exhaled hydrogen peroxide is due to neutrophils via the conducting airways. In contrast, the production of exhaled nitric oxide seems to be primarily associated with monocytes.

[Chemoprevention of lung cancer. A review about previous studies, results and future developments]. / Chemoprävention beim Bronchialkarzinom: Uberblick über bisherige Studien, Ergebnisse und zukünftige Entwicklungen.

Despite improvements in the early detection of lung tumors, mortality from this type of disease is increasing world wide and the 5-year-survival rate still ranges below 10 %. The approach of chemoprevention offers the possibility to interfere with the process of cancerogenesis by the use of natural or synthetic chemical compounds and either to prevent DNA damage or to stepp the proliferation of premalignant cells that are already in place. With regard to bronchial carcinoma, chemoprevention in the first place implies cessation of smoking but the currently used procedures are not extremely efficient and many ex-smokers experience an increased risk of acquiring a lung tumor over a prolonged period of time (secondary prevention). In the past 20 years many details of the process of tumorigenesis have been revealed and this knowledge has promoted the targeted use of chemopretective compounds. In addition to the classics in the fields, such as vitamin A, beta-carotene, vitamins E, C and B12 as well as selenium, the last years have brought the development of new compounds, such as retinoids, dithiols, cyclooxygenase inhibitors, epidermal growth factors and others, the mechanismen of action of which provide interesting new approaches. In addition, the introduction of biomarkers, either genetic alterations or proliferation or differentiation, allows to monitor the process of tumorigenesis in its different stages, from early to late, and thereby offers the perspective to perform studies on chemoprevention more rapidly and effectively as in previous years. Thus, in combination with optimized, controlled study designs it is to be expected that in near future clinical studies on the effects on chemoprotective compounds will yield decisive data on their efficacy in chronic smokers as well as ex-smokers.

Phase II study with paclitaxel for the treatment of advanced inoperable non-small cell lung cancer.

Paclitaxel is a plant product isolated from the bark of the Western yew (Taxus brevifolia) that promotes the formation and stabilization of microtubules. This leads to growth arrest in the G2/M phase of the cell cycle. Paclitaxel has demonstrated significant antineoplastic activity in different tumor types, most notably in ovarian and breast carcinoma. In two Phase II trials (Eastern Cooperative Oncology Group [ECOG]/M.D. Anderson) in patients with previously untreated Stage IIIB-IV non-small cell lung cancer (NSCLC), response rates of 21% and 24% were reported. We are performing a Phase II trial investigating the efficacy of paclitaxel in patients with inoperable Stage IIIB-IV NSCLC. Forty-three patients were treated, 31 males and 12 females, with a median age of 59 years (range, 29-75), ECOG performance status 0-2, Stage IIIB 30%, Stage IV 70%. Patients were treated every 3 weeks with 225 mg/m2 as a 3-h infusion with standard premedication. Preliminary efficacy results from 37 patients include partial remissions in eight (21.6%) patients, no change in 22 (59.5%) and disease progression in seven (19%) patients. Eight patients are still receiving therapy. The hematologic toxicities (n = 43) were mild, and no World Health Organization (WHO) Grade 4 neutropenia was observed. Nonhematologic toxicities were Grade 1/2 polyneuropathy in 97.6%, Grade 1-3 myalgia/arthralgia in 76%, and Grade 1-3 nausea/vomiting in 18.6% of the patients. In conclusion, paclitaxel is an active single agent in this patient population. Mild hematologic toxicities were observed in the 3-h infusion setting (compared with 24-h infusion) and therapy was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of cancer weight loss in patients with advanced lung cancer.

Megestrol acetate, a semisynthetic gestagen, is effective not only for endocrine therapy of advanced breast carcinomas, but also in the treatment of cachectic patients with aggressive, hormone-independent tumors. Sixty-six patients with therapy-resistant, advanced bronchogenic carcinomas of different histologic types, who had lost more than 10% of their regular body weight within a prospective, randomized trial, were treated with megestrol acetate at a dose of either 160 or 480 mg/day for 3-4 months. The mean weight gain for all patients was 2.5 kg. Nearly all of them (80%) reported improved appetite and well-being. The mean weight gain in the group of patients receiving 480 mg/day was higher (3.0 kg) than in the group receiving 160 mg/day (2.0 kg).

A randomized trial with mitomycin-C/ifosfamide versus mitomycin-C/vindesine versus cisplatin/etoposide in advanced non-small-cell lung cancer.

192 evaluable patients with advanced inoperable non-small-cell lung cancer were treated with either mitomycin-C/ifosfamide (A), mitomycin-C/vindesine (B), or cisplatin/etoposide (C) in a prospective randomized trial. The response rates for each treatment arm were 30.0% (A), 22.7% (B), and 25% (C), respectively. There was no statistically significant difference (p = 0.4) between treatment arms. The median survival time was 27 weeks (A), 23 weeks (B), and 25 weeks (C), respectively. With regard to toxicity the combination mitomycin-C/vindesine was superior to treatment arms A and C. Nausea and vomiting (WHO 3 + 4) occurred only in 6.1% of the patients versus 43.3% of those treated with mitomycin-C/ifosfamide and 36.7% of those treated with cisplatin/etoposide. This difference is statistically highly significant (p = 0.0001). Because of its very low toxicity, especially for gastrointestinal symptoms, the combination mitomycin-C/vindesine was judged superior to the other combinations. None of these regimens, however, had a major impact on survival in advanced non-small-cell lung cancer.

Intrapleural palliative treatment of malignant pleural effusions with mitoxantrone versus placebo (pleural tube alone).

From 11/87 until 7/90 103 patients entered a prospective randomized trial on the treatment of malignant pleural effusions (MPE) with intrapleural mitoxantrone versus placebo (pleural tube alone with instillation of isotonic NaCl). Our data suggest no statistically significant difference between the two arms with respect to response and response duration. There is no influence on survival time. The toxicity is moderate, with only fever occurring more often in the mitoxantrone arm. We recommend performance of pleurodesis in patients with MPE first by sufficient drainage with a tube of 16-20 char. Only in instances of failure it is necessary to add sclerosing agents such as tetracycline, etc.

Megestrol acetate in cachectic patients with advanced bronchogenic cancer.

Megestrol acetate, a semisynthetic gestagen, is effective not only for endocrine therapy of advanced breast carcinoma, but also in treatment of cachectic patients with aggressive, hormone-independent tumors. 40 patients with therapy-resistant, advanced bronchogenic carcinoma of different histologic type, who had lost more than ten percent of their regular body weight within a prospective, non-randomized trial were treated with megestrol acetate at a dose of either 160 mg/day or 480 mg/day for 3-4 months. The average weight gain of all patients was 3.0 kg. Nearly all of them (80%) reported improved appetite and well-being. The weight gain in the group of patients receiving 160 mg/day was higher (80%) than in the group receiving 480 mg/day (50%), suggesting that the lower dose is as effective as the higher one for palliative treatment.

[Leu-M1, CEA and intermediate filament proteins in histochemical differential diagnosis of malignant pleural mesothelioma]. / LEU-M1, CEA und Intermediärfilamentproteine in der histochemischen Differentialdiagnose maligner Pleuramesotheliome.

The differential diagnosis "pleuramesothelioma" vs "metastatic adenocarcinoma" can mostly not be decided clearly by conventional histological methods in malignant pleuraneoplasias. Leu-M1 is employed in immunhistochemical diagnosis of lymphomas in Hodgkin's disease but it also reacts with adenocarcinoma cells. Pleuramesotheliomas are Leu-M1 negative. Intermediary filament proteins, CEA and Leu-M1 are important "markers" in the diagnosis of malignant pleuraneoplasias. 25 pleura biopsies of malignant pleura processes were subjected to immunhistochemical examination.

Phase II studies with carboplatin in non-small cell lung cancer.

Since 1987, we have evaluated carboplatin alone or in combination with etoposide in two separate phase II trials of patients with non-small cell lung cancer (NSCLC) who had not received prior chemotherapy. Single-agent carboplatin produced a 20% response rate in 51 patients treated with 390 mg/m2 intravenously every 4 weeks. A 3-day schedule of etoposide 140 mg/m2 on days 2, 3, and 4, and carboplatin 150 mg/m2 on days 1 and 5 also resulted in a 26.7% response rate in 46 patients. Myelosuppressive toxicity associated with carboplatin/etoposide was substantially greater than that seen with carboplatin alone. Carboplatin as a single agent is active in previously untreated patients with advanced NSCLC. The two-drug combination of carboplatin and etoposide also shows activity in NSCLC similar to other combination chemotherapeutic regimens based on comparable prognostic factors in untreated patients. Further evaluation of carboplatin as part of combination chemotherapy in NSCLC is warranted.

[Cisplatin-Vepeside versus Endoxan-Vepeside in the treatment of small cell bronchial cancer. A randomized study]. / Cisplatin-Vepesid versus Endoxan-Vepesid in der Behandlung kleinzelliger Bronchialkarzinome. Eine randomisierte Studie.

Within the framework of a multi-centre prospective randomised therapeutic trial, 150 patients with small-cell lung cancer (SCLC) were treated with cisplatin/vepesid and endoxan/vepesid. The aim of the study was to establish whether cisplatin--which although effective is commonly associated with adverse effects--can be replaced by endoxan. The sequence of treatment was oriented to the stage and course of the tumour disease. In the event of a treatment failure, cross-over to the alternative combination was effected. In terms of remission rates, the combination cisplatin/vepesid proved to be more effective than endoxan/vepesid, in particular in the case of patients with extensive disease. With respect to duration of remission and survival duration, however, no significant differences were to be seen.

[Chemotherapy of advanced non-small cell bronchial cancer with mitomycin C/ifosfamide versus mitomycin C/vindesine versus cisplatin/etoposide--a prospective randomized study]. / Chemotherapie des fortgeschrittenen nicht-kleinzelligen Bronchialkarzinoms mit Mitomycin-C/Ifosfamid versus Mitomycin-C/Vindesin versus Cisplatin/Etoposid--Eine prospektiv randomisierte Studie.

In a prospective randomised study involving patients with inoperable non-small-cell lung cancer, no differences were to be seen in the remission rates (30.3%, 22.7% and 25%, respectively; p = 0.4) achieved by the combinations mitomycin/ifosfamide, mitomycin/vindesine and cisplatin/etoposide. Nor were any statistically significant differences to be found in terms of the duration of survival. The median survival durations were 6.5, 5.5 and 6 months, respectively (p = 0.7). With respect to toxicity, the combination mitomycin/vindesine proved to be superior, in particular since virtually no gastrointestinal toxicity was observed with this combination. On the basis of these results and the-state of our knowledge to date, the conclusion may be drawn that cisplatin-containing combinations should no longer be employed in the chemotherapeutic treatment of non-small-cell cancers.

[Chemotherapy of small cell bronchial cancer with a combination of carboplatin, vincristine and etoposide]. / Die Chemotherapie des kleinzelligen Bronchialkarzinoms mit einer Kombination aus Carboplatin, Vincristin und Etoposid.

In a phase II study, the combination of the new platinum derivative carboplatin with vincristine and etoposide is associated with a remission rate of 81.8 per cent (LD 84.4%, ED 79.1%). The median survival rates for patients with limited disease have not yet been reached, and, at 11.5 months in the case of patients with extensive disease, are unexpectedly high. In comparison with combinations containing cisplatin, the present combination would appear to be superior, and its toxicity is also lower. For a definitive assessment of its usefulness, it must be compared with other standard treatment regimens in prospective, randomized studies.

[Carboplatin-Vepeside in the treatment of non-small cell bronchial cancers. A phase II study]. / Carboplatin-Vepesid in der Behandlung nicht kleinzelliger Bronchialkarzinome. Eine Phase II Studie.

Carboplatin, a derivative of cisplatin, has, when administered alone, a remission rate of almost 20 per cent. Forty-six patients were treated with the combination carboplatin/vepesid. Twenty-seven per cent of the patients experienced partial remission; in 41%, no change in the size of the tumour was observed. Neither alone nor in combination does carboplatin appear to show any nephrotoxicity or otoxicity, and its neurotoxic effect is only slight.

Phase II study of carboplatin in untreated, inoperable non-small-cell lung cancer.

A total of 51 previously untreated patients with non-small-cell lung cancer (NSCLC) were treated with 130 mg/m2 carboplatin given every 4 weeks as an i.v. infusion on days 1, 3, and 5. Ten patients achieved a partial response and five, a minor response. The overall response rate was 20% (95% confidence limits, 8%-32%). The median duration of response was 3 months and the median overall survival was 4.5 months. Leucopenia, thrombocytopenia and anemia of WHO grade 3 occurred in 4%-6% of patients and grade 3 nausea and vomiting was observed in 8% of our subjects. Grade 4 thrombocytopenia occurred in 3 (6%) patients. Apart from nausea and vomiting, nonhematologic toxicities above grade 2 were not observed. Further trials using carboplatin in NSCLC as a single agent or in combination with other chemotherapeutic agents or radiation are warranted.

Airway responsiveness to methacholine does not change during chemotherapy in patients with chronic bronchitis and bronchial carcinoma.

To investigate the role of leukocytes and neutrophils in the peripheral blood on airway responsiveness, we studied nine patients with chronic bronchitis and histologically proved bronchial carcinoma before and after chemotherapy. The concentration of methacholine (in mg/ml) necessary to increase specific airway resistance by 100%, PC100SRaw, and the number of leukocytes and neutrophils (in cells x 10(6)/ml) were measured before, and 8 and 16 days after chemotherapy. Mean (SEM) total number of leukocytes decreased significantly (p less than 0.001) from 9.0 (0.8) to 4.4 (0.6) and 3.4 (0.4), and mean (SEM) number of neutrophils decreased significantly (p less than 0.005) from 5.1 (0.7) to 2.8 (0.5) and 1.0 (0.4), respectively. Mean (SEM) PC100SRaw was 3.3 (0.9) at baseline and 3.5 (1.2) and 3.8 (1.0) mg/ml at Days 8 and 16, respectively, without significant differences. These data suggest that a significant chemotherapy-induced leukocyte depletion in the peripheral blood does not influence airway responsiveness in patients with chronic bronchitis and bronchial carcinoma.

Pulmonary metastasizing hemangiopericytoma.

Hemangiopericytomas are rare tumors, originating from pericytes of the small vessels, that can appear anywhere in the body. From the histological picture it is difficult to determine whether or not they are malignant. The metastasizing rate depends upon the tumor's location and varies from 50 to 80%. Local recurrences occur in roughly 50% of the cases. Hemangiopericytoma is normally surgically treated because radio- and chemotherapy are generally less effective. There is limited experience in treating metastasizing hemangiopericytomas with chemotherapy. We treated 2 patients with pulmonal metastasizing hemangiopericytoma: In 1, the tumor originated in the brain and in the other, the left knee. Both patients had chemotherapy over an extended period of time. By means of x-ray, histological, and electronmicroscopical examinations we report on the course of the diseases.

[Abdominal pseudotumor as the clinical manifestation of Whipple's disease. T-cell index as an indicator of disease activity and a parameter of the duration of therapy?]. / Abdominaler Pseudotumor als klinische Manifestation eines Morbus Whipple. T-Zell-Index als Indikator der Krankheitsaktivität und Parameter der Therapiedauer?

A large nonresectable upper-abdominal tumor in a 61-year-old woman was found to have been caused by inflammatory infiltration and mechanical obstruction of the mesenteric lymph nodes resulting in obstruction to lymphatic flow. Biopsy at the root of the mesentery and of abdominal lymph nodes raised the suspicion of Whipple's disease, a diagnosis confirmed by a small-intestine biopsy. Long-term antibiotic treatment was successful. Quantitative changes in the composition of the T-cell subpopulations at the time of the diagnosis reverted to normal in the course of treatment.

Predominant cutaneous infiltration by OKT6- and OKT8-positive cells in a case of Sézary syndrome.

Using an immunoperoxidase (skin biopsy) and an immunofluorescence (peripheral blood, bone marrow punctate) technique, and monoclonal antibodies raised against peripheral mature lymphocytes, T helper subsets, T suppressor subsets, and Langerhans cells, we found a predominant dermal infiltration with lymphocytes of the suppressor phenotype and a predominant epidermal infiltration with Langerhans cells in a patient with Sézary syndrome (cutaneous T-cell lymphoma, CTCL). Repeated peripheral blood examinations showed an increased percentage of lymphocytes of the helper phenotype. A bone marrow examination revealed a ratio of suppressor/helper subsets of 1:4. The findings in the skin seem to be inconsistent with most of the results of previous studies in patients with CTCL; the significance of these findings is discussed.

[Carcinomas in papillary cystadenolymphomas of the parotid gland--definition and differential diagnosis (author's transl)]. / Carcinome in Papillären Cystadenolymphomen der Parotis Definition und Differentialdiagnose.

Within a collective of 1431 salivavry gland tumors of the salivary gland register (1965--1976) an observation has been done, which has been classified as a "carcinoma in a papillary cystadenolymphoma". Corresponding to the "carcinoma in a pleomorphous adenoma" of the WHO-classification of salivary gland tumors the terminus "carcinoma in a cystadenolymphoma" is further defined. 6 additional cases from the literature are reviewed. The possible role of epithelial metaplasia and of a proceding radiation in the development of carcinomas in cystadenolymphomas are discussed. The following other tumors have to be differentiated from a carcinoma in a cystadenolymphoma: Metastases of other tumors beyond a cystadenolymphoma; malignant lymphoepithelial lesions (predominantly malignant lymphomas in a preexisting immune-sialadenitis of the myoepithelial sialadenitis type; rare carcinomas), and lymphoepitheliomas.