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The sensitivity and specificity of Cyfra 21-1 as marker for lung cancer was evaluated in comparison with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). Patients with histologically verified lung cancer and different groups without lung cancer were investigated. Sensitivity of Cyfra 21-1 (cut-off level 2.9 micrograms/l) was 40% for non-small cell lung cancer (NSCLC), 60% for rare histological types and 21% for small cell lung cancer (SCLC). In NSCLC sensitivity of Cyfra 21-1 was 35% for squamous cell carcinoma and 41% for adenomous carcinoma. The highest sensitivity for CEA was 45% in NSCLC, with 57% in the subtype of adenomous cell carcinoma; for SCC 30% was achieved in squamous cell carcinoma and for NSE 66% sensitivity was reached in SCLC. In our patients Cyfra 21-1 and CEA appeared equally useful for evaluating patients with NSCLC.

Thirty-eight patients with metastatic renal-cell carcinoma (RCC) and 1 patient with a second primary RCC were treated with coumarin and cimetidine. Patients received 400 mg cimetidine p.o. daily and after 1 week 100 mg coumarin p.o. daily in addition until tumour progression. Two complete remission (30 and 50+ months) and 3 partial remissions (14, 13.8 months) could be achieved. Problems regarding possibly spontaneous regressions and comparable results of other treatment in RCC are discussed.

From 1975 to 1977 42 patients with advanced solid tumours were treated with imidazole-carboxamide (DTIC). It was applied in 18 cases as monotherapy: in the remaining patients it was administered in combination with other cytostatic agents. Tumour remission was recorded in 4/22 patients with melanoma, 2/2 with Kaposi sarcoma and 2/7 with soft tissue sarcoma. No change in tumour behaviour was recorded in 6/22 melanomas, 2/7 soft tissue sarcomas, 1/7 head and neck tumours and 1/1 thymoma. Side effects of DTIC monotherapy were comparably low. The optimum dosage and frequency of DTIC therapy have not yet been established. Combinations with other cytostatic agents are still being tested.

Intraarterial infusionstherapy was performed with cytostatic agents (10 patients) and proteolytic enzymes (4 patients) in 14 selected cases with malignant lung tumours. Diagnosis was in 8 patients small cell carcinoma, in 3 patients adenocarcinoma, in 2 patients squamous cell carcinoma of the lung and in 1 patient leiomyosarcoma of the lung (relapse). Infusions were performed in 8 cases through the A. bronchialis, in 5 through the A. pulmonalis and in 1 patient through the A. thoracica interna. After single infusions of cytostatic agents via the A. bronchialis, remissions of varying extents, were found in 5 out of 8 patients. Repeated infusions with enzymes (1-5 series) through the A. pulmonalis lead in 2 out of 4 cases to slight remissions with a duration of 5 and 12 months, respectively. Possibilities and limiting factors of this therapeutic modality are demonstrated by recent observations.

The results of a prospective randomized study on carcinoma of the bronchus are reported. In a total of 56 patients polychemotherapy, high-dosage vitamin-A treatment, Endoxan and immunotherapy, as well as the application of proteolytic enzymes in altogether 5 combinations of therapy were tested.

A new synthetic compound 4-imino-1,3-diazobicyclo (3,1,0)-hexan-2-on (BM 06 002) has been shown in animal models to stimulate humoral and cell-mediated immune reactions. In a Phase I study in man a total absence of toxic side effects after intravenous injection of BM 06 002 has been demonstrated. In the present investigation in patients with advanced incurable cancer one single injection of this substance induced a significant stimulation of lymphocyte blastogenesis response to PHA and PWM. Delayed cutaneous hypersensitivity reactions, tested before and after drug application, were also found increased. According to thses findings BM 06 002 might be considered as an immune-stimulating compound.

55 selected patients with inoperable small cell carcinoma of the lung have been induced in a randomized prospective trial in order to compare the efficacy of ifosfamide monotherapy with the combination of ifosfamid + CCNU. Initially a control group, treated with symptomatic therapy only, was also included but preliminary analysis revealing that results were unfavourable in comparison to those of the chemotherapy group; this treatment arm was omitted. 53 of 55 patients were evaluable. In group 1 (symptomatic therapy) results were better as to patients' quality of life, but no tumor remissions have been observed and survival times were significantly shorter (15 to 122 days; geometric mean 42.35 days). In group 2 (ifosfamide monotherapy) one total remission (lasting 15 months) and 2 partial remissions (lasting from 3 weeks to 4 months) have been achieved; in this group survival was 3 to 473 days (geometric mean 110.15 days). In group 3 (ifosfamide + CCNU) 7 partial remissions have been observed (3 weeks to 4 months), survival was 17 to 477 days (geometric mean 107.32 days). The combination of ifosfamide with CCNU did not reveal any advantage in comparison to ifosfamide monotherapy.

From 1970 to 1976, 268 patients with pleural effusions underwent local therapy with the polyenzyme preparation Wobemugos; 235 patients were evaluable regarding the effectiveness of this therapy. In 115 of the cases, the primary tumour was carcinoma of the bronchus, in 86, carcinoma of the breast, in 9, mesothelioma and carcinoma of the ovary each, and in 16, other malignancies. There was a total remission of pleural effusions in 42% of the cases, a partial one in 41%, and no effect in 17%. In spite of the relatively large number of patients, some difficulties in interpreting the present results still remain and will be discussed in this paper.

In a prospective randomized study 78 selected patients with bronchogenic cancer have been included, and five different treatment modalities have been compared (1. Biologic therapy; 2. Vitamin A + Cytoxan; 3. Vitamin A + Telecobalt irradiation; 4. Telecobalt irradiation; 5. Immunotherapy). No significant differences if survival times between the different groups have been observed. Nevertheless, significant differences of survival times were found between small cell and squamous cell carcinoma patients without respect to the therapy applied. The highest number of remissions was obtained by therapy 3, followed by 4 and 2. Consequences for further studies are discussed.

Based on a clinical trial, in which patients with unresectable bronchogenic cancer were treated with a combination of vitamin A plus chemotherapy, or vitamin A plus radiotherapy, a study was initiated in which vitamin A alone was given for tumor treatment. 9 male patients with metastatic unresectable squamous cell carcinoma of the lung were treated with vitamin A palmitate or 13-cis vitamin A acid. Up to seven treatment courses were given during a period of 60 weeks. Through weekly evaluation of the patients' immune status, an immune potentiating effect of the vitamin A therapy could be demonstrated. An increase of lymphocyte blastogenesis response to PHA which is significant (p less than 0.001) compared with the pretreatment values, was found in all patients at the end of one vitamin A treatment course. Increased delayed cutaneous hypersensitivity reactions were observed also in all patients. The immune potentiating effects of vitamin A therapy, as well as the demonstrated direct effect on the tumor, introduces a wide range of combination therapies.

Non-small cell lung cancer (NSCLC) is less responsive to chemo- and radiotherapy than bronchogenic small cell cancer. Until now the results of chemotherapy in NSCLC have been disappointing. In a retrospective study on epidermoid cell lung cancer we can show that there is no increase of the survival time during the last 22 years. In a total of 2425 patients the median survival time ranged from 179 to 299 days each year, without any trend. Because of the poor therapeutic results and the accompanying toxicity, which deteriorates survival quality, the cytostatic treatment of NSCLC is still an unsolved problem.

Clinical experiences obtained until now in the treatment of 47 patients with small cell carcinoma of the bronchus with Holoxan are reported. Special emphasis is laid to the results of a prospective randomized study; two groups of patients, one of them undergoing Holoxan therapy, the other receiving symptomatic treatment, have been investigated in respect of relationship between tumour remission, quality of life and survival time.

The long-term results are presented of cytostatic treatment with a combination of adriamycin + methotrexate + vincristine + trofosfamide in 45 patients with advanced inoperable epidermoid cell lung cancer. The overall response rate (complete + partial remission) was 13/45 = 29%; the survival time from the beginning of therapy ranged from 12 to more than 1023 days, with a median of 166 days. Three patients are still alive. The group with non-keratinising epidermoid cell cancer showed a significantly longer survival time than the group with keratinising tumours. Therapy was accompanied by side effects in all patients, whereby the intensity of side effects was inversely correlated with the clinical outcome of therapy. An analysis of the individual response of patients revealed a positive effect of therapy in 19 patients (very good in 13 and good in 6) whereas a negative effect was found in 12 patients (very poor in 10 cases); in 14 cases the effect was questionable. The overall poor results of cytostatic therapy in epidermoid cell lung cancer so far are pointed out and, on the basis of the presented data, its implementation routinely outside oncogenic centres does not appear to be warranted.

In untreated patients with inoperable lung cancer, serum levels of alpha1-antitrypsin were found significantly increased in comparison to patients with non malignant diseases of the lung, alpha2-macroglobulin levels were unchanged in both groups of patients. There was also no difference in alpha2-macroglobulins in cancer patients reacting with DNCB and in non-reactors. Thus alpha2-macroglobulin levels do not seem to correlate with the immunestatus of cancer patients. Proteinase inhibitors are involved in a variety of biological processes including blood, clotting, digestion, and sperm capacitation. alpha1-antitrypsin, a alpha-globulin with a molecular weight of about 60,000 has been found to be decreased in patients' serum under several pathological conditions. A clear correlation exists between alpha1-antitrypsin deficiency and hereditary pulmonary emphysema (1, 2), respiratory distress syndrome (3), and juvenile cirrhoses of the liver (4). Elevated serum levels of alpha1-antitrypsin have also been found in some cancer cases. Thirty years ago a cancer test was developed on the basis of differences in the antiproteolytic activity in cancer patients' sera and in patients with other non-neoplastic diseases (5, 6). Several authors have tried to confirm these early data regarding specifity and sensitivity with respect to a screening test for cancer (7, 8). Methods of these authors were based mainly on enzyme substrate inhibition assays by addition of the patients' sera. Recently a commercially available test, based on immune-precipitation according to Mancini (9), has been developed (Behring-Werke, Partigen). By using this standardized method for determinating alpha1-antitrypsin, Harris et al. have recently demonstrated that patients with inoperable lung cancer have significantly elevated levels of this antiprotease in their sera (10), in comparison to patients with non malignant diseases of the lung. alpha2-macroglobulin is a serum protein with a molecular weight of 800,000 and with known antiprotease activity and can therefore bind trypsin, plasmin, elastase, and collagenase and it is known that alpha2-macroglobulin decreases with increasing of age. Changes of alpha-macroglobulin have also been observed in several pathological conditions (11). James et al. 4ave found decreases in serum of myeloma patients (12). An association between the development and function of lymphocytes and alpha2-macroglobulin has been suggested by several authors (13, 14). This alpha2-globulin has also been demonstrated on the surface of peripheral blood lymphocytes (15) and there is evidence that it is synthesized by lymphocytes (16). The purpose of the present study was to determine serum alpha1-antitrypsin levels in patients with inoperable lung cancer and to determine whether there is also an inverse correlation to alpha2-macroglobulin. It was further attempted to correlate alpha2-macroglobulin with general immunological parameters, as it is known that patients with lung cancer show a decreased general immune-reactivity (17).