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Biomedical subjects

P Dombernowsky

Publications and source records attributed to P Dombernowsky.

At least 163 records · Page 9Linked to original sources
PubMed1983

A phase III trial comparing prednimustine (LEO 1031) to chlorambucil plus prednisolone in advanced breast cancer.

Prednimustine is an ester of chlorambucil and prednisolone. The drug has had some activity in experimental as well as in human tumors, including breast cancer. The objective of the current study is to compare the clinical effectiveness and toxicity of prednimustine with its components of chlorambucil plus prednisolone, and to compare the clinical effectiveness and toxicity of a continuous treatment with an intermittent one. Two hundred and one patients with advanced breast cancer were randomized to the following treatments: I: prednimustine continuously; 40 mg/m2 d; II: prednimustine intermittently, 160 mg/m2 d 1 to 5, repeated every three weeks; and III: chlorambucil 8 mg/m2 d plus prednisolone 8 mg/m2 d, both given continuously. All treatments were given orally. One hundred and ninety five patients were evaluable for assessment of response to the treatments. The response rates were 21% in both of the prednimustine-treated groups, whereas only 11% of the patients treated with chlorambucil and prednisolone responded. The duration of remission with continuous prednimustine was longer than with the other two treatment groups, but not significantly so. One hundred and ninety five patients were evaluable for assessment of hematologic toxicity. No differences were observed between the two prednimustine-treated groups, whereas the group treated with chlorambucil plus prednisolone experienced a significantly higher degree of leukopenia and/or thrombopenia. Subjective toxicities, nausea, vomiting and psychical symptoms were only moderate in the three treatment groups, but significantly more pronounced in the group treated with intermittent prednimustine. Because of these promising results, prednimustine should be compared to other alkylating agents in patients with advanced breast cancer in randomized trials.

Adult↗
PubMed1983

Brain CT-scanning and neurological examination in small cell bronchogenic carcinoma.

A brain CT-scan and a neurological examination were performed on forty-nine consecutive patients with small cell bronchogenic carcinoma before the start of chemotherapy and every three months thereafter. Contrast-enhancement was used in 90% of the CT-scans. Ninety percent of the neurologic examinations were performed by the same neurologist. No prophylactic cranial irradiation was given, and cranial irradiation was withheld if a CT-scan indicated metastases, unless the patient was symptomatic. Thirty-five patients are evaluable including 34 with a brain autopsy. CNS-metastases were found in 18 patients. Two of them had not been examined within three months of autopsy and are excluded from the calculations of diagnostic accuracy. Of the remaining 16 patients 10 had a correct diagnosis of cerebral metastases made by CT-scan, while the neurologist made 11 correct diagnoses of CNS-metastases. Seventeen patients did not have CNS-metastases including one patient alive and free of disease. Fifteen and 11 were judged to be free of metastases by the CT-scan and the neurologist, respectively. Two patients with negative autopsies had positive CT-scans turning negative at subsequent examinations. Two had positive CT-scans which became negative and at autopsy CNS-metastases were located at different sites from those initially indicated by CT. The positive predictive value of CT-scan was 71%, while the negative predictive value was 71%. In conclusion, routine CT-scan and neurological examination are equally sensitive but have low yields when there is no clinical suspicion of CNS-metastases. The predictive value of CT-scanning could possibly be higher with the newer generations of equipment.

Aged↗
PubMed1983

Phase-I study of alpha-1,3,5-triglycidyl-s-triazinetrione (NSC 296934).

alpha-1,3,5-Triglycidyl-s-triazinetrione (TGT) is a triepoxide derivative with alkylating properties discovered by random screening. TGT has been found to be active against a wide variety of murine tumors, including a P388 subline resistant to cyclophosphamide. The starting dose in this phase-I study was 30 mg/m2 as a single dose IV, repeated every 3-4 weeks, increasing up to 2,700 mg/m2. Severe dose-limiting toxicity took the form of phlebitis becoming apparent a few days after treatment. This was initially seen at the 480 mg/m2 dose level, and was observed with increasing frequency and intensity at higher dose levels. Leukopenia occurred regularly at dose levels above 1,800 mg/m2 and resulted in life-threatening leukopenia in one patient, and in a toxic death at 2,700 mg/m2 in another patient. Other toxic side-effects included moderate reversible thrombocytopenia, nausea, and vomiting. It is recommended that further trials with TGT await the development of more water-soluble formulations or of other triepoxide derivatives.

Adult↗
PubMed1983

Effects of intensive chemotherapy on respiratory function in patients with small cell carcinoma of the lung.

The lung function of 30 consecutive patients with small cell carcinoma of the lung was evaluated before and 3 months after initiation of intensive chemotherapy. Radiological evaluation of the therapeutic effect on the lung tumor was possible in 19 patients after 3 months. Six patients achieved complete normalization of the chest X-ray, 10 patients achieved more than 50% reduction of the tumor and no or minimal changes in the radiological image were observed in 3 patients. Before treatment a mixed pattern of obstructive and restrictive lung disease was observed in all patients. In the 16 patients who achieved partial or complete remission of the tumor normalization of the total lung capacity (P less than 0.02), vital capacity (P less than 0.02), FEV1 (P less than 0.02) and PEF (P less than 0.05) was observed independently of the degree of shrinkage of the tumor on chest roentgenogram, thus suggesting that the tumor was the major cause of the lung function impairment in these patients. The diffusion capacity and parameters reflecting the function of the small airways (RV/TLC% and MEF50) remained abnormal after treatment. Improvement of the lung function did not predict the individual duration of survival. However, the study proved that roentgenological normalization is paralleled by physiological normalization with the current treatment of this disease.

Adult↗
PubMed1983

A phase II trial of peplomycin in squamous cell carcinoma of the lung.

A phase II trial has been performed in squamous cell carcinoma of the lung using peplomycin. This compound is a bleomycin analogue with less pulmonary toxicity and a broader antitumor effect than bleomycin in experimental animal systems. Twenty-one evaluable patients were treated using a dose schedule of 5 mg/m2 twice weekly intravenously. None of the patients had previously received radiation or chemotherapy. The median dose of peplomycin received was 160 mg (range 45-254). One patient obtained a partial remission lasting 3 months. One out of 21 patients developed clinical symptoms and a decrease in the lung function test performed during treatment indicative of toxicity. Other manifestations of toxicity are comparable to those of bleomycin.

Aged↗
PubMed1983

Role of radiation therapy in small cell anaplastic carcinoma of the lung.

The previously established roles of radiotherapy in the management of small cell anaplastic carcinoma of the lung have changed with the development of improved chemotherapy. A group of the International Association for the Study of Lung Cancer has concluded that while there is established evidence that the addition of chemotherapy improves the results of radiation therapy, the value of the addition of loco-regional radiation therapy to chemotherapy is uncertain and more difficult to assess. No advantage in short-term (median) survival has been shown in randomized studies, but current data suggest a possible advantage in long-term control of loco-regional disease. Further results of prospective trials are needed to resolve this question. Prophylactic cranial irradiation reduces the incidence of cerebral metastases but so far has not resulted in improved survival. Pending the results of further randomized studies, its routine use in all patients is not advocated. The palliative role of radiation therapy is valuable in symptomatic treatment. Various current modifications of technique to improve the results of conventional radiation treatments with an altered fractionation schedule and use of sensitizers and large fields are not believed to show major advantages. The clear documentation of treatment details and the definition of the criteria for the assessment of results are important if further comparisons of results are to be made possible. In particular, the need for reporting long-term survival at 2 years in contrast to the more usual median survival time is stressed.

Antineoplastic Agents↗
PubMed1983

Phase II study of vinblastine in small cell carcinoma of the lung.

Thirty-five patients with small cell carcinoma of the lung, refractory to previous combination chemotherapy including vincristine, were treated with weekly iv bolus injections of vinblastine. The dose was 4 mg/m2 in the first 22 patients and 7 mg/m2 in the last 13. No responses were observed among 34 evaluable patients. Side effects included moderate leukopenia and minimal neurotoxicity. It is concluded that vinblastine appears to be inferior to other vinca alkaloids in the treatment of small cell carcinoma of the lung.

Adult↗
PubMed1983

Continuous versus alternating combination chemotherapy for advanced small cell carcinoma of the lung.

In a 2-year period, 146 patients with small cell carcinoma of the lung, staged as having extensive disease, were randomized to receive either continuous chemotherapy consisting of (a) 1-(2-chloroethyl-3-cyclohexyl-1-nitrosourea, cyclophosphamide, methotrexate, and vincristine followed by (b) 4'-demethylepipodophyllotoxin 9-[4,6-O-(R) ethylidene-beta-D-glucopyranoside] and doxorubicin at progression of disease or a regimen of (a) alternating with (b). Seventy-six patients received the continuous regimen; 70 patients received alternating treatment. Response rates were 68 and 72%, respectively. The median duration of response was 16 weeks in patients receiving continuous treatment compared to 28 weeks in patients receiving alternating treatment (p less than 0.05). No survival time difference was observed between the groups, median survival being 36 and 38 weeks, respectively. Four patients became long-term survivors (5.6 +, 5.5 +, 5.1, and 4.7 + years). All received alternating therapy. Six toxic deaths were observed among patients receiving continuous therapy compared to only one death among those in the alternating regimen. In conclusion, alternating combination chemotherapy leads to prolonged duration of remission. Duration of survival is not prolonged in uncured patients, but an increased possibility of long-term disease-free survival cannot be precluded.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

Normalization of defective monocyte chemotaxis during chemotherapy in patients with small cell anaplastic carcinoma of the lung.

Monocyte chemotactic responsiveness (MCR) in 14 patients with small cell anaplastic bronchogenic carcinoma was depressed before treatment compared with the MCR in 28 normal controls (P = 0.00004). MCR was subsequently monitored during combination chemotherapy and after 6 months the MCR had become normalized compared with pretreatment values (P = 0.00006). In addition, chemotactic factor inhibitor (CFI) activity in plasma was measured before treatment and after 6 months. When incubated with plasma before treatment casein had 62% of normal activity and when incubated with plasma after chemotherapy, 81% of normal activity (P = 0.0009). CFI activity decreased by greater amounts in patients in complete remission than in patients in partial remission or in non-responders (P = 0.01). This study supports the concept that cancer patients have depressed monocyte function. Chemotherapy seems to enhance monocyte chemotaxis in vitro and to decrease CFI activity in plasma.

Adult↗
PubMed1982

A quantitative and qualitative study of blood monocytes in patients with bronchogenic carcinoma.

Absolute circulating number and functions of blood monocytes (i.e., pinocytosis, phagocytosis, and chemotaxis) were studied in 25 patients with untreated bronchogenic carcinoma and in 28 control subjects. The absolute circulating monocyte count was increased in 20 (80%) of the patients. There was no difference in the pinocytic and phagocytic activity of patient and control monocytes. In contrast, patient monocytes showed depressed chemotactic responsiveness. This defect was more severe in small cell anaplastic carcinoma than in the other histologic types of bronchogenic carcinoma (P = 0.0001), and may explain the difference in macrophage infiltration seen in solid tumours of the lung. There was no correlation between chemotaxis and clinical stage. Depressed chemotaxis may be related to a plasma factor, since patient plasma inhibited the chemotaxis of control monocytes as well as the activity of chemotactic agents. The defective chemotaxis and the presence of plasma inhibitory activity may interfere with the ability of blood monocytes to accumulate as macrophages in tumour sites.

Adult↗
PubMed1982

Phase II trial of amsacrine (m-AMSA) in advanced ovarian carcinoma.

A phase II study of 4'-(9-acridinylamino)methanesulfon-m-anisidide (amsacrine, m-AMSA) was carried out in previously treated patients with advanced ovarian carcinoma. The dose of amsacrine was 90 mg/m2 every 3 weeks in 34 patients having received prior extensive chemotherapy and/or radiotherapy, and 120 mg/m2 in 5 patients who had previously only received moderate amounts of chemotherapy. Among patients evaluable for response the median number of courses was 3 (range 2-17). Two patients (5%) experienced complete response for 15+ months. Leucopenia was the most frequent toxic effect. WBC nadir was 2700/mm3 (range 1000-7300). Other toxic effects were of lesser significance and included thrombocytopenia, anemia, nausea and vomiting. It is concluded that amsacrine has only marginal activity in patients with previously treated ovarian carcinoma.

Adult↗
PubMed1982

Phase II study of procarbazine in small cell carcinoma of the lung.

Thirty-nine patients with small cell anaplastic carcinoma of the lung were given oral doses of procarbazine ranging from 100 to 200 mg/m2 on Days 1-14 every 4 weeks. All patients had previously received combination chemotherapy. No responses were observed in the 24 evaluable patients. In reviewing the literature, we were unable to find evidence that the inclusion of procarbazine in combination chemotherapy is beneficial in small cell anaplastic carcinoma. Accordingly, it is concluded that procarbazine should not be considered as a useful drug in the management of this cell type of lung cancer.

Administration, Oral↗
PubMed1982

Vindesine in the treatment of squamous cell carcinoma, adenocarcinoma, and large cell carcinoma of the lung.

The antineoplastic activity of vindesine was evaluated in a phase II trial in patients with squamous cell carcinoma, adenocarcinoma, and large cell carcinoma of the lung. Sixty-three patients participated in the trial: 22 with squamous cell carcinoma, 25 with adenocarcinoma, and 16 with large cell carcinoma. Most of the patients had not received prior treatment; six had received single-agent chemotherapy. The dose of vindesine was 4 mg/m2 every 2 weeks, reduced or increased according to hematologic and neurologic side effects. Fifty-four patients were evaluable. Objective response was observed in two of 19 patients with squamous cell carcinoma (11%), in six of 22 patients with adenocarcinoma (27%), and in one of 13 patients with large cell carcinoma (8%). In patients with adenocarcinoma the median duration of response was 196 days (range, 71-450+). Twenty-five percent of the evaluable patients received greater than or equal to 100% of the scheduled dose. In 39% of the patients, dose reductions were necessary because of leukopenia, and in 63%, dose modifications were necessary because of neurotoxic effects. It is concluded that vindesine as a single-agent chemotherapy is active against adenocarcinoma of the lung. Activity in squamous cell carcinoma and large cell carcinoma appears to be less, but not totally absent.

Adenocarcinoma↗
PubMed1981

Hypouricaemia and inappropriate secretion of antidiuretic hormone in small cell bronchogenic carcinoma.

Hypouricaemia has been observed in patients with the syndrome of inappropriate secretion of antidiuretic hormone (IADH). Accordingly, 69 patients with untreated bronchogenic small cell carcinoma were examined for IADH. Serum urate was also measured. IADH was proven in 25 (35%) of the 69 patients. The median serum concentration of urate in these patients was 0.26 mmol/l (range 0.13-0.50), compared to 0.36 mmol/l (0.21-0.60) in the 44 patients without IADH. The difference is statistically significant (p less than 0.01), but serum urate--when used alone--is lacking in both sensitivity and specificity for the diagnosis of IADH.

Carcinoma, Bronchogenic↗