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Biomedical subjects

P Dombernowsky

Publications and source records attributed to P Dombernowsky.

At least 145 records · Page 8Linked to original sources
PubMed1986

Medroxyprogesterone acetate and prednisone in advanced breast cancer. A randomized trial.

In a randomised trial patients with progressive metastatic breast cancer were allocated to one of three different treatments. A: Prednisone 10 mg X 3 daily. B: Medroxyprogesterone acetate (MPA) orally 500 mg daily. C: MPA i.m. 1000 mg daily for 3 weeks followed by 500 mg i.m. weekly. The study included 150 patients and was well-balanced with respect to different prognostic parameters. Most patients (83%) were postmenopausal, and 95% had previously received chemo- or hormonal therapy. In the MPA treated patients, analysis of serum MPA levels was performed once a month. The response rates were 4.6, 7.9 and 12.5% in treatments A, B and C, respectively. This difference was not statistically significant (P greater than 0.05). Furthermore, the follow-up of serum MPA levels revealed no significant difference between responders and non-responders. Analysis of time to progression did not indicate any advantage of MPA over prednisone, irrespective of MPA schedule. In accordance with these data, there was no difference as regards survival in the three groups. In conclusion, the study indicated that MPA is not superior to prednisone in this group of heavily pretreated patients with advanced breast cancer.

Administration, Oral↗
PubMed1986

Influence of surgical resection prior to chemotherapy on the long-term results in small cell lung cancer. A study of 150 operable patients.

The effect of surgical resection, prior to chemotherapy, on the long-term results obtained in treatment of operable patients with small cell lung cancer (SCC) was evaluated in a consecutive series of 874 patients treated with intensive combination chemotherapy with or without irradiation between 1973 and 1981. Evaluation of disease stage and operability was based on broncho-mediastinoscopy, chest X-ray, bone marrow examination, peritoneoscopy with liver biopsy and lung function tests. The same staging procedures were applied for restaging performed after 18 months of chemotherapy. The series comprised 440 patients with extensive disease and 437 with limited disease of whom 150 were regarded operable. Fifty-four operable patients received no thoracotomy because the treatment policy of SCC did not include surgery at the hospitals from which they were referred. These patients served as a reference with which data on operated patients were compared. Resections were performed in 52 patients while 44 were regarded to be irresectable at the thoracotomy. Thirty-six resections were regarded histologically complete while 16 patients proved to have microscopic (9 pts) or macroscopic (7 pts) residual tumor. The number and per cent of 30 months disease-free survivors in the various categories of the 874 patients were as follows: Completely resected, 12/36 patients (33%); Resected with residual tumor, 2/16 (12.5%); Operable but non-operated, 7/54 (13%); Irresectable, 3/44 (6.8%); Non-operable patients with limited disease, 15/284 (5.3%) and with extensive disease, 11/440 (2.5%). The similarity between rates of long-term survival observed in resected patients with residual tumor and operable, non-operated patients suggests that resection, per se, has no significant influence on long-term results in SCC. The relatively high rate of long-term survival in completely resected patients may therefore primarily be a result of early stage disease at the initiation of chemotherapy.

Carcinoma, Small Cell↗
PubMed1986

Chemotherapy versus chemotherapy plus irradiation in limited small cell lung cancer. Results of a controlled trial with 5 years follow-up.

One hundred and forty-five patients with limited stage small cell lung cancer were included in a randomized trial to evaluate the effect of chemotherapy with or without chest irradiation. Seventy-six patients were allotted chemotherapy alone while 69 patients received the same chemotherapy plus radiotherapy, 40 Gy in split-course, administered in weeks 6 and 10 after the initiation of chemotherapy. The chemotherapy consisted of lomustine, cyclophosphamide, vincristine and methotrexate. Patients treated with chemotherapy alone survived for a median of 52 weeks compared to 44 weeks in patients receiving the combined regimen (P = 0.055). After exclusion of five early deaths and one patient refusing the irradiation plus 14 completely resected patients, the remaining 65 patients receiving chemotherapy alone and the 60 patients treated with chemotherapy plus radiotherapy were included in a new analysis. The difference in survival duration which could be ascribed to treatment with or without chest irradiation thereby diminished (P = 0.24). Eighteen months' disease-free survival was obtained in 9.2% of the 65 patients and in 9.8% of the 60 patients. The complete remission rates were 37% and 46%, respectively, (P = 0.33) and the median durations of complete remission were 40 weeks and 52 weeks (P = 0.67). Treatment failure of the primary tumour occurred in 85% of patients treated with chemotherapy alone in contrast to 61% of patients receiving the combined regimen (P = 0.005). Seventy-nine of these patients underwent autopsy at which no residual chest disease was observed in 17% and 37%, respectively (P = 0.045). The combined regimen was more toxic than chemotherapy alone resulting in significantly greater dose reductions and more pronounced thrombocytopenia. Lung and pericardial fibrosis was responsible for four deaths among the complete responders in the radiotherapy group. The combined regimen thus tended to be more efficacious with respect to tumour control at the expense, however, of increased toxicity which per se, eliminated a potential improvement of the overall therapeutical results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Teniposide (VM-26), an overlooked highly active agent in small-cell lung cancer. Results of a phase II trial in untreated patients.

Teniposide, VM-26 (Vumon), was administered in a dose of 60 mg/m2 on days 1 to 5 every third week to 36 patients with histologically confirmed small-cell lung cancer. None had previously received chemotherapy or radiotherapy. The median age was 73 years (range, 52 to 79). Thirty-three patients were evaluable; 21 of these had local disease. Five patients had bone marrow metastases, four had liver involvement, and one CNS metastases. All patients had a performance status less than or equal to 2 before the start of treatment. Thirty patients obtained a response (90%), ten of whom had a complete remission (30%). The median duration of remission was 8+ months (range, 1.1 to 17+ months), whereas the median survival was 8.7 months (range, 1.9 to 20 months). Toxicity was primarily hematologic, with leukopenia the only dose-limiting effect. Besides alopecia, all other side effects were minimal including nausea and vomiting. We find these results provocative in regard to the response rate and the duration of response obtained as well as in reference to the dismal results that prior investigations in previously treated patients have shown. These data may indicate the need for reconsideration of the usual strategy for performing phase II trials.

Aged↗
PubMed1986

Mortality and morbidity in long-term surviving patients treated with chemotherapy with or without irradiation for small-cell lung cancer.

Mortality and morbidity was investigated in a consecutive series of 72 patients with small-cell lung cancer (SCLC) who were found to be disease-free at restaging after 18 months of treatment. These patients were all the long-term survivors among 874 patients included in one of six trials between 1973 and 1981. All studies used combination chemotherapy with or without irradiation. Follow-up of the patients varied between 4 and 11 years. The estimated 5-year survival rate subsequent to discontinuation of therapy was 0.24, corresponding to a death rate of 0.25 per year or ten times greater than the expected mortality for persons of the same age group. This high mortality was primarily related to recurrent SCLC, the estimated cumulative risk of relapse reaching 46% at the time of the latest recurrence 5 years from diagnosis. The risk of relapse was generally independent of the pretreatment disease stage although it was reduced in patients with resectable disease and was greater in those with pretreatment liver or bone marrow metastases. Equal risks of relapse were related to the use of regimens with and without radiotherapy. The cumulative risk of relapse in patients surviving 3 years from initiation of the treatment was less than 15% and accordingly, 3 years of follow-up seems sufficient for comparison of long-term results obtained in different trials. The second factor resulting in death or disease was second cancer, for which the cumulated risk increased to 32%, the latest occurring 5.4 years from the diagnosis of SCLC. Five of these cases were non-small-cell lung cancers and three were secondary leukemias. The estimated mortality related to non-neoplastic conditions was just significantly greater than expected. In spite of the increased mortality in this series, 38 of 54 2-year disease-free survivors and 20 of 22 5-year survivors resumed a lifestyle similar to that before diagnosis of SCLC.

Aged↗
PubMed1986

Long-term disease-free survival in small-cell carcinoma of the lung: a study of clinical determinants.

The influence of treatment and of pretreatment patient characteristics on the probability of long-term disease-free survival in small-cell lung cancer (SCLC) was investigated in a consecutive series of 874 patients. The patients were included in six controlled treatment trials from 1973 to 1981, using different combinations of chemotherapy with or without irradiation. All patients underwent pretreatment staging, including bronchoscopy, peritoneoscopy with liver biopsy, and bone marrow examination. The same procedures were repeated in patients without overt signs of disease 18 months from initiation of treatment, and patients without evidence of SCLC were regarded as long-term survivors. Seventy-two patients were disease-free at restaging, corresponding to 13% of 443 patients with limited-stage disease and 3% of 431 patients with extensive-stage disease. The possible relationship between different pretreatment variables and the probability of 18 months' disease-free survival was investigated by multiple regression analysis. Disease extent was the most important determinant of long-term survival. Being a woman was a positive factor and hypouricemia had negative influence on the long-term results, while features such as performance status and serum lactate dehydrogenase (LDH) did not have significant influence in the regression model. Differences between the efficacy of the applied treatment regimens were less in limited disease than they were in extensive disease, in which six-agent regimens of alternating chemotherapy was significantly better than treatment with three- or four-agent regimens. Accordingly, disease extent seems to be the most pivotal determinant of long-term survival in SCLC, but influence of the patient's sex and serum urate concentration should also be considered.

Adolescent↗
PubMed1986

Combined endocrine treatment of postmenopausal patients with advanced breast cancer. A randomized trial of tamoxifen vs. tamoxifen plus aminoglutethimide and hydrocortisone.

The therapeutic efficacy of combined endocrine therapy with tamoxifen, aminoglutethimide and hydrocortisone (T+AG+H) was evaluated against treatment with tamoxifen (T) alone in 210 patients above 65 years of age with metastatic breast cancer. The treatment results have been assessed for the 166 fully evaluable patients and were the following for the T and T+AG+H groups, respectively: PD: 31 and 35%; NC: 35 and 37%; PR: 13 and 16%; and CR: 21 and 12%. The overall treatment results are not statistically different (p = 0.35) and the 95% C.L. of the difference of the response rates are -8% to +20%. The median duration of remission was approximately 24 months in both treatment groups (p = 0.31). The time to treatment failure was comparable with median values of 10 and 8 months in the T and the T+AG+H groups respectively (p = 0.17). Toxicity was more frequent and severe in the combined treatment group and could in most instances be attributed to treatment with AG+H. In conclusion, the simultaneous use of T and AG and H does not seem to improve the therapeutic results in postmenopausal patients with advanced breast cancer.

Aged↗
PubMed1986

Adjuvant tamoxifen in postmenopausal high-risk breast cancer patients: present status of Danish Breast Cancer Cooperative Group trials.

The aim of the present study was to analyze the efficacy of adjuvant tamoxifen (TAM) in postmenopausal patients with high-risk breast cancer. The primary surgical treatment was total mastectomy with axillary sampling. There were 1,650 eligible patients; 829 were randomized to receive postoperative radiotherapy (RT) and 821, to receive RT + TAM (10 mg three times daily for 1 yr). The 2 groups were identical with respect to age, tumor size, number of positive lymph nodes, degree of anaplasia, and estrogen and progesterone receptor content. Overall recurrence-free survival at 6 years was 39% in the RT group, compared to 48% in the RT + TAM group (P = 0.0008), but there was no significant difference in survival (P = 0.14). From retrospective analyses of recurrence-free survival according to prognostic variables, it appears that 4 subgroups of patients benefited from adjuvant TAM: those less than 69 years of age, those with 4 or more positive nodes, those with grade I-II tumors, and those with high estrogen receptor values (greater than 100 fmol/mg cytosol protein).

Aged↗
PubMed1985

A randomized study of single agent vs combination chemotherapy in FIGO stages IIB, III and IV ovarian adenocarcinoma.

From 1977 until 1980, 179 patients with newly diagnosed FIGO stages IIB, III or IV ovarian adenocarcinoma were randomized in a two-armed clinical trial: dihydroxybusulfan (B) 600 mg/m2 p.o. for 4-6 weeks q 12 weeks or cyclophosphamide (C) 150 mg/m2 p.o. for 7 days q 4 weeks vs a combination of cyclophosphamide 400 mg/m2 i.v., doxorubicin 30 mg/m2 and 5-fluorouracil 400 mg/m2 i.v., days 1 and 8 q 4 weeks (CAF). In addition, stage IIB patients were randomised to +/- pelvic irradiation. The patients were stratified according to anatomic stage. The treatment groups were comparable with respect to performance status, age and histology. Twenty-three patients were excluded because of protocol violation, leaving 156 patients evaluable for survival with an observation period of 3-6 yr. Twenty patients were in stage IIB, while the remaining 136 patients were classified as stages III and IV. No statistically significant difference was found in survival or response between the two single agents. The overall median response rate (single drug: 27%; CAF: 47%) and the median response duration (single drug: 5 months; CAF: 10 months) were significantly superior for the CAF group compared to the single agent group. No statistical difference in median survival was observed between single-drug treatment (12 months) and CAF (14 months), despite the fact that responders lived significantly longer than nonresponders (17 vs 10 months). In stage IIB patients receiving chemotherapy no benefit of pelvic irradiation was found. Thirty patients (19%) underwent second-look laparotomy, with 15 (50%) being completely free of disease. So far only one patient (7%) has relapsed. Two additional patients, who had microscopic disease removed at second-look laparotomy, seem to have been rescued by this procedure.

Adenocarcinoma↗
PubMed1985

Treatment policy of surgery in small cell carcinoma of the lung: retrospective analysis of a series of 874 consecutive patients.

A therapeutic policy of surgery in the treatment of small cell carcinoma of the lung was evaluated in a retrospective series of 874 consecutive patients. All patients were included in one of six clinical trials of intensive combination chemotherapy and radiotherapy, carried out during 1973-81. General criteria of resectability, including normal appearances at mediastinoscopy, were fulfilled in 33 electively operated patients and in 46 non-operated patients. An elective operation was defined as a thoracotomy performed with the intention of pulmonary resection in a patient known to have small cell carcinoma. Pneumonectomy or lobectomy was performed in 73% of the electively operated patients. Residual macroscopic or microscopic tumour tissue was left after half of these resections. Both operated patients and non-operated patients with operable tumours survived significantly longer than 696 patients deemed to have been inoperable. There was no significant difference, however, in the duration of survival between the two subsets of operable patients. According to this analysis, a treatment policy of surgery for resectable small cell carcinoma does not lead to better overall results than treatment with chemotherapy and radiotherapy alone.

Actuarial Analysis↗
PubMed1984

Randomized phase II trial of carminomycin versus 4'-epidoxorubicin in advanced breast cancer.

Sixty-three evaluable patients with advanced breast cancer were randomly allocated to receive three-week intravenous courses of carminomycin (18 mg/m2) or 4'-epidoxorubicin (90 mg/m2). The former yielded one (3%) partial response for nine weeks among 29 patients whereas, in the other arm, nine (27%) of 34 patients achieved partial response for a median of 28 weeks (range, nine to 36 weeks; p less than 0.02). The major toxic effect of these anthracyclines was leukopenia with median white blood cell nadirs of 1,600/microL (range, 300-4,000/microL) versus 1,800/microL (range, 500-4,300/microL), respectively. Acute nonhematologic toxic effects were qualitatively similar but carminomycin produced significantly less gastrointestinal intolerance and alopecia. Patients whose disease failed to respond to first-line anthracycline received doxorubicin (60 mg/m2) every three weeks. Four partial responses were obtained among 19 patients previously treated with carminomycin. Following 4'-epidoxorubicin therapy, one of 12 evaluable patients also attained partial response. Survival curves were not affected by the initial treatment option. Carminomycin has marginal activity against breast cancer whereas 4'-epidoxorubicin deserves further evaluation of its therapeutic index relative to doxorubicin. The design used in this trial appears attractive for prompt phase II evaluation of anthracycline analogs.

Adult↗
PubMed1984

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

Fifty-one patients with small cell bronchogenic carcinoma received 60 mg/m2 of teniposide iv on Days 1-5 every 3 weeks. All patients had received previous combination chemotherapy. Twenty patients with prior etoposide treatment and 20 without such prior treatment were evaluable. A partial response was observed in one of 20 and in five of 20 patients, respectively. The duration of responses was short (28-50 days). Sixty-one percent of patients experienced grade 3 or 4 toxicity on the World Health Organization scale. The activity in previously treated patients not exposed to etoposide was considerable, justifying further evaluation of teniposide in the treatment of small cell carcinoma of the lung.

Adult↗