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Biomedical subjects

P Dombernowsky

Publications and source records attributed to P Dombernowsky.

At least 181 records · Page 10Linked to original sources

Long-term survival in small cell carcinoma of the lung.

From June 1973 to August 1977, three hundred thirty-seven patients with small cell carcinoma of the lung were included in randomized therapeutic trials. By February 1979, fifty-one patients (15%) had survived for 18 months, including 29 (9%) in clinical complete remission. Of the latter patients, readmitted for restaging, including bone marrow examination, peritoneoscopy, and bronchomediastinoscopy, residual tumor was found in four. Treatment was discontinued in the remaining patients; six subsequently had relapses, while three patients died, free of disease, of other causes. Sixteen patients are still alive and free of disease more than 19 to 50 months after the primary diagnosis; seven were treated with combination chemotherapy alone, including four who initially had distant metastatic disease. The remaining nine patients had regional disease and were treated with both chemotherapy and radiotherapy, including prophylactic brain irradiation in four patients. Long-term survival can be achieved in a small number of patients in all stages of small cell carcinoma with intensive combination chemotherapy.

Carcinoma↗

Phase II trial of prednimustine, L-1031, (NSC-134087) in advanced breast cancer.

The therapeutic effect of prednimustine was studied in 35 patients with advanced breast cancer resistant to previous cytotoxic and/or endocrine therapy. Response (PR + CR) was obtained in 14 patients (40%) of a median duration of five months. Among the 14 responding patients, 10 were resistant to previous endocrine therapy and chemotherapy, in all cases including alkylating agents, and 4 were resistant to previous endocrine therapy. Hematologic toxicity was rather pronounced, but other toxicities were only moderate.

Adult↗

Prophylactic irradiation in bronchogenic small cell anaplastic carcinoma. A comparative trial of localized versus extensive radiotherapy including prophylactic brain irradiation in patients receiving combination chemotherapy.

A total of 114 patients with bronchogenic small cell anaplastic carcinoma and staged as having regional disease all underwent combination chemotherapy consisting of CCNU, cyclophosphamide, and methotrexate. They were randomized to receive either radiotherapy to the primary tumor and regional lymph nodes (4000 rad) or extensive radiotherapy, which included the brain, adrenals, and upper retroperitoneal lymph nodes. Fifteen patients were free of disease after 18 months of chemotherapy and the treatment was discontinued. Only 3 patients subsequently relapsed. No difference was observed between the two groups of patients in median survival time, response rate, duration of response or relapse pattern, including the frequency of brain metastasis.

Adult↗

The epipodophyllotoxin derivatives VM-26 and VP-16-213, 1976-1979, a review.

The epipodophyllotoxin derivatives VM 26 and VP 16-213 are currently entering phase III studies. The mechanism of their action is incompletely understood, but the greatest lethal effect is experienced in the late S and G2 phases. In transplanted tumors both drugs have shown marked schedule dependency and human studies also support this. As a single agent VP 16-213 is among the most active drugs in small-cell carcinoma of the lung. Significant clinical activity (> 20% response frequency) has been observed for both drugs in Hodgkin's disease, non-Hodgkin lymphomas and possibly in other more rare tumors (monocytic leukemia, hepatoma and teratoma). Although further clinical studies of both drugs would be ideal, it seems possible at present to justify a discontinuation of VM-26 in order to concentrate the efforts on VP 16-213. Further studies are needed to define optimal dose and schedule and place in combination chemotherapy.

Animals↗

Phase II trial of prednimustine (NSC-134087) in the treatment of small-cell anaplastic carcinoma of the lung.

In a phase II trial, the clinical activity of prednimustine, an ester of chlorambucil and prednisolone, was evaluated in 28 patients with small-cell anaplastic carcinoma of the lung. Prednimustine was given at dose levels ranging from 130 to 220 mg/m2/daily for 5 days every 3 weeks. Among 19 previously treated patients no responses were observed, while responses of 2, 2, and 3 months' duration were seen in three of nine previously untreated patients more than 70 years old. The toxicity took the form of mental disturbances in six patients, while the hematologic toxicity was mild. The therapeutic effectiveness of prednimustine in small-cell carcinoma of the lung is thus limited although some activity is observed in previously untreated patients.

Aged↗

Peritoneoscopy in the staging of 190 patients with small-cell anaplastic carcinoma of the lung with special reference to subtyping.

Peritoneoscopy with liver biopsy was routinely done as a pretreatment staging procedure in 190 patients with small-cell anaplastic carcinoma of the lung. Subtyping of the patients according to the WHO classification included 28.3% with fusiform cell type (WHO II,1), 28.9% with polygonal cell type (WHO II,2), 41.5% with lymphocytelike cell type (WHO II,3) and 1.3% with mixed types (WHO II, 4). Liver metastases were found in 21% of the patients with adequate liver biopsy. In addition macroscopic signs of liver metastases were observed in 9%. No significant differences were observed among the histological subtypes. Liver function tests, such as alkaline phosphatase, LDH and GOT, were of little value in excluding liver metastases. On the other hand, 2 of 3 abnormal liver function tests were highly indicative of liver metastases. In patients with positive liver biopsy, 41% had liver metastases alone and 76% had no other evidence of distant metastatic disease if bone-marrow involvement identified with bone marrow examination is excluded as a staging procedure.

Adult↗

Combination chemotherapy in the management of superior vena caval obstruction in small-cell anaplastic carcinoma of the lung.

Among 225 consecutive patients with small-cell anaplastic bronchogenic carcinoma, 26 (11.5%) had superior vena caval obstruction when the malignancy was diagnosed. Of these 26 patients, a consecutive series of 22 were treated initially with combination chemotherapy (cyclophosphamide, methotrexate and CCNU, in some cases combined with vincristine) alone, and in all these cases resolution of the syndrome was prompt within a median of 7 days. In no case were symptoms increased transiently by the treatment. No difference in response rate was observed between the histologic subtypes of small-cell anaplastic bronchogenic carcinoma according to the WHO classification. Combination chemotherapy alone is an effective treatment of superior vena caval obstruction in patients with small-cell anaplastic bronchogenic carcinoma.

Aged↗

Chemotherapy of advanced small-cell anaplastic carcinoma. Superiority of a four-drug combination to a three-drug combination.

A controlled clinical trial compared three-drug and four-drug combination chemotherapy in 109 patients with advanced small-cell anaplastic carcinoma of the lung. The combination of vincristine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cyclophosphamide, and methotrexate was significantly superior to the combination of the last three drugs alone with regard to median survival (230 versus 176 days) (P less than 0.01) and to duration of response (186 versus 112 days) (P less than 0.01). Objective response occurred in 78% and 75%, respectively. No significant difference in these values was observed in the comparison of the three subtypes of small-cell anaplastic carcinoma using the World Health Organization classification.

Aged↗

Bone-marrow examination in the staging of small-cell anaplastic carcinoma of the lung with special reference to subtyping. An evaluation of 203 consecutive patients.

Histologic examination of bone-marrow from the posterior iliac crest was routinely done as a pretreatment staging procedure in 203 consecutive patients with small-cell anaplastic carcinoma of the lung. Subtyping of the patients according to the WHO classification included 27.8% with "fusiform" cell type (WHO II,1), 28.3% with "polygonal" cell type (WHO II,2), 42.8% with "lymphocyte-like" cell type (WHO II,3), and 1.1% with mixed types (WHO II,4). Bone-marrow involvement was found in 17.2%. No significant difference was observed among the histological subtypes with regard to bone-marrow involvement. A comparison of bone-marrow biopsy and aspiration in patients investigated with both procedures showed that aspiration alone was diagnostic in nine of 24 (38%) positive patients as compared with two of 24 (8%) with biopsy alone, while in the remaining 13 patients (54%) both procedures were positive. Of the 35 patients with positive bone-marrow examination, 77% had no other evidence of distant metastatic disease if liver metastases identified by peritoneoscopy and liver biopsy are excluded as a staging procedure. With the exception of thrombocytopenia which was observed in six patients, with bone-marrow metastases, hematological findings were of little value in detecting bone-marrow involvement.

Adult↗

Treatment of small cell anaplastic carcinoma of the lung with the oral solution of VP-16-213 (NSC 141540, 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside).

The semisynthetic podophyllotoxin derivative VP-16-213 (NSC 141540) has been evaluated in a phase II study in patients with small cell anaplastic carcinoma of the lung. The drug was administered as an oral solution, the drinking ampoule, in doses of 100 mg twice a day for 4 days in 30 patients previously treated with intensive combination chemotherapy and for 5 days in 10 untreated patients. The courses were repeated every third week with dose modifications according to individual tolerance. All patients had measurable disease and objective responses were obtained in 20 patients (50%), 15 previously treated (50%) and 5 untreated patients (50%). The median time for response after the start of treatment was 15 days (range 6-42) and the median duration of response was 56 days (range 16-147). Dose-limiting toxicity was principally hematologic, consisting of leukopenia, but gastrointestinal toxicity and alopecia were also observed. The study demonstrated that VP-16-213 administered as an oral solution is highly effective against small cell anaplastic carcinoma of the lung without clinical cross-resistance to CCNU, cyclophosphamide, methotrexate, or vincristine.

Administration, Oral↗

Cell proliferation and histologic classification of bronchogenic carcinoma.

The rate of cell proliferation of 99 bronchogenic carcinomas (94 primary tumors and 5 metastases) was evaluated from the labeling index after in vitro incorporation of [3H]thymidine; the rate was then correlated with the histologic tumor type according to the classification of the World Health Organization (WHO). Cell proliferation was significantly slower in adenocarcinoma (WHO type III) than in squamous cell carcinoma (WHO type I), small cell anaplastic carcinoma (WHO type II), and large cell carcinoma (WHO type IV). Cells proliferated at a significantly higher rate in large cell carcinoma than in the squamous cell type, whereas no significant difference was observed between the other cell types. Dedifferentiated forms of squamous cell carcinomas had a higher rate of cell proliferation than did differentiated forms of the same cell type. Metastases of small cell anaplastic carcinoma did not differ in cell proliferation from primary tumors of the same cell type.

Adenocarcinoma↗