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P Dombernowsky

Publications and source records attributed to P Dombernowsky.

At least 91 records · Page 5Linked to original sources
PubMed1992

Adjuvant radiotherapy and risk of contralateral breast cancer.

BACKGROUND: The risk of contralateral breast cancer is increased twofold to fivefold for breast cancer patients. A registry-based cohort study in Denmark suggested that radiation treatment of the first breast cancer might increase the risk for contralateral breast cancer among 10-year survivors. PURPOSE: Our goal was to assess the role of radiation in the development of contralateral breast cancer. METHODS: A nested case-control study was conducted in a cohort of 56,540 women in Denmark diagnosed with invasive breast cancer from 1943 through 1978. Case patients were 529 women who developed contralateral breast cancer 8 or more years after first diagnosis. Controls were women with breast cancer who did not develop contralateral breast cancer. One control was matched to each case patient on the basis of age, calendar year of initial breast cancer diagnosis, and survival time. Radiation dose to the contralateral breast was estimated for each patient on the basis of radiation measurements and abstracted treatment information. The anatomical position of each breast cancer was also abstracted from medical records. RESULTS: Radiotherapy had been administered to 82.4% of case patients and controls, and the mean radiation dose to the contralateral breast was estimated to be 2.51 Gy. Radiotherapy did not increase the overall risk of contralateral breast cancer (relative risk = 1.04; 95% confidence interval = 0.74-1.46), and there was no evidence that risk varied with radiation dose, time since exposure, or age at exposure. The second tumors in case patients were evenly distributed in the medial, lateral, and central portions of the breast, a finding that argues against a causal role of radiotherapy in tumorigenesis. CONCLUSIONS: The majority of women in our series were perimenopausal or postmenopausal (53% total versus 38% premenopausal and 9% of unknown status) and received radiotherapy at an age when the breast tissue appears least susceptible to the carcinogenic effects of radiation. Based on a dose of 2.51 Gy and estimates of radiation risk from other studies, a relative risk of only 1.18 would have been expected for a population of women exposed at an average age of 51 years. Thus, our data provide additional evidence that there is little if any risk of radiation-induced breast cancer associated with exposure of breast tissue to low-dose radiation (e.g., from mammographic x rays or adjuvant radiotherapy) in later life.

Adult↗
PubMed1992

Carbohydrate antigen 549 in metastatic breast cancer during cytostatic treatment and follow-up.

This study was designed to investigate whether the serum tumour marker CA 549 gave early and reliable information about disease activity among metastatic breast cancer patients during cytostatic treatment and follow-up. 50 females with metastatic breast cancer were monitored clinically and with the tumour marker CA 549. Response evaluation was based upon clinical (World Health Organization) and elaborated CA 549 criteria, respectively. In 113 blindly and matched evaluations, concordance appeared in 73/113 and discordance in 40/113 evaluations. In 27, discordance concerned degree of response, in 2 clinical progression followed marker progression after the end of the study, and in 11 progressive disease was established by clinical investigation alone. CA 549 response excluded clinical progression in bone or viscera and reversed. Clinical progression within 2 months in viscera and bone was predicted among 91% by marker progression. Clinical progression was excluded among 93% without marker progression. In conclusion, monitoring of metastatic breast cancer patients could include CA 549 if standardised criteria for marker evaluation are used.

Adult↗
PubMed1992

Teniposide in advanced breast cancer. A phase II trial in patients with no prior chemotherapy.

The objective response rates were determined using teniposide as first-line chemotherapy for patients with recurrent breast cancer. Twenty-seven evaluable patients with advanced disease received teniposide 70 mg/m2 i.v. days 1-5 every 3 weeks. A total of 211 courses were given. Responses included one complete (4%) and 9 partial responses (33%) with a median duration of response of 9 months (range 2-31 months). The main toxicity was myelosuppression. The results show that teniposide has at least modest activity in patients with advanced breast cancer treated previously with endocrine therapy.

Aged↗
PubMed1992

Metastatic spinal cord compression secondary to lung cancer.

PURPOSE: Metastatic spinal cord compression (MSCC) is a disabling complication to cancer, the optimal treatment for which is not settled. An analysis was performed for all patients with MSCC secondary to lung cancer in East Denmark from 1979 to 1988. PATIENTS AND METHODS: The total series included 102 cases with small-cell carcinoma (SCLC; 40%), adenocarcinoma (ACL; 26%), squamous cell carcinoma (SQLC; 18%) and large-cell carcinoma (LCC; 9%). Symptoms, clinical presentations, and therapeutic results are described. RESULTS: The outcome of treatment depended fundamentally on the patient's neurologic condition at the time of the diagnosis. All patients with SCLC who were able to walk at the time of MSCC remained ambulatory, whereas 15% of the nonambulatory SCLC patients regained walking ability. In non-SCLC, 95% of patients continued to be able to walk, whereas 22% regained the ability to walk. No major differences in the immediate outcome of treatment between the various histologic types of lung cancer and the different treatment modalities were observed; however, 82% of the patients with non-SCLC benefited from treatment with laminectomy followed by radiotherapy (RT) compared with either laminectomy (47%) or RT (39%) alone (P = .03, chi 2 test). The group of patients who were treated with laminectomy followed by RT had a better survival (median value, 3.5; range, 0 to 132 months) than patients who were treated with either laminectomy (median value, 1.5; range, 0 to 32 months) or RT (median value, 1; range, 0 to 59 months) alone (P = .03, log-rank test). No significant difference was observed in survival between the various histologic types of lung cancer (P = .18, log-rank test). CONCLUSION: Despite a short survival, early diagnosis and immediate treatment is crucial because it may preserve the gait function in 97% of lung cancer patients who develop malignant spinal cord compression.

Adenocarcinoma↗
PubMed1992

Acute monocytic or myelomonocytic leukemia with balanced chromosome translocations to band 11q23 after therapy with 4-epi-doxorubicin and cisplatin or cyclophosphamide for breast cancer.

PURPOSE: To report five cases of acute monocytic or myelomonocytic leukemia after chemotherapy with 4-epidoxorubicin for breast cancer and to evaluate the risk of leukemia after the use of this drug. PATIENTS AND METHODS: One hundred fifty-seven patients with advanced breast cancer were randomized to either 4-epi-doxorubicin plus cisplatin or 4-epi-doxorubicin alone. An additional 203 patients were treated prospectively with 4-epi-doxorubicin alone. All were observed closely for leukemic complications. RESULTS: Three patients from the randomized study developed leukemia; all were in the subgroup of 74 patients who received 4-epi-doxorubicin plus cisplatin, whereas no leukemia was observed among the remaining 83 patients in the randomized study or among the additional 203 patients who were treated prospectively with 4-epi-doxorubicin alone (P = .023, log-rank test). In the subgroup of 74 patients who were treated with 4-epi-doxorubicin plus cisplatin, the cumulative risk of leukemia was 16.0% +/- 9.9% (mean +/- SE) 33 months after the start of therapy; the relative risk was 668 (95% confidence interval [Cl], 138 to 1,953). Two other cases of acute monocytic and myelomonocytic leukemia were observed after 4-epi-doxorubicin plus alkylating agents were administered for breast cancer. Three of five cases of leukemia presented balanced translocations to chromosome band 11q23 and two, loss of a whole chromosome no. 7 or its long arm. CONCLUSIONS: 4-epi-doxorubicin is leukemogenic, and the leukemias are often acute monocytic or myelomonocytic with balanced chromosome translocations to band 11q23, such as in the leukemias after therapy with the epipodophyllotoxins. Furthermore, our results suggest a synergistic effect in leukemogenesis between 4-epi-doxorubicin targeting DNA-topoisomerase II and directly genotoxic drugs such as cisplatin or alkylating agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Teniposide in the treatment of small cell lung cancer: a review.

The epipodophyllotoxin derivatives teniposide and etoposide have been under clinical investigation for over 15 years. Although etoposide has been established as one of the most active compounds in the treatment of small cell lung cancer (SCLC), teniposide has received little attention. The results of seven phase II studies evaluating response rate and duration of response to teniposide in 10 previously treated and 102 untreated patients showed response rates of 21% and 58%, respectively. The most frequently used dosage schedule was 60 mg/m2 intravenously daily for 5 days every 3 weeks. The following are factors influencing the response rate and duration of response to teniposide: performance status; prior weight loss; prior chemotherapy exposure, including prior treatment with etoposide; stage; and effectiveness of prior chemotherapy, including time from last administration. Preliminary analyses from a study comparing the efficacy of teniposide with that of etoposide suggest that teniposide may be more effective in previously untreated patients with SCLC who are 70 years of age or older. The preliminary data, however, indicate that equivalent doses of teniposide cause more cases of leukopenia than etoposide. Before a final conclusion can be drawn, the results from an ongoing study using teniposide and etoposide at equitoxic doses must be evaluated.

Carcinoma, Small Cell↗
PubMed1992

Experience with ifosfamide in the EORTC Soft Tissue and Bone Sarcoma Group.

The Soft Tissue and Bone Sarcoma Group of the European Organization on Research and Treatment of Cancer has conducted a number of studies of chemotherapy in advanced disease over the past 15 years. Following the discovery that the CYVADIC regimen (cyclophosphamide/vincristine/doxorubicin/dimethyl imidazole carboxamide) was less active than had been reported originally, the individual components of CYVADIC were studied. This showed that doxorubicin had considerable activity and that ifosfamide 5 g/m2 given over 24 hours was at least as active as cyclophosphamide. Subsequent studies have therefore centered on a combination of doxorubicin and ifosfamide. A large randomized trial showed no significant benefit of doxorubicin/ifosfamide over single-agent doxorubicin, but the doses of doxorubicin were different. More recently, using bone marrow growth factors, it has been possible to increase the doxorubicin dose to that given as a single agent and also maintain the ifosfamide dose. This is now being tested in a randomized trial to determine whether improved response rates and other indicators of outcome will be seen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Classical prognostic factors in node-negative breast cancer: the DBCG experience.

Classical prognostic factors were analyzed in patients with low-risk primary breast cancer, defined as absence of tumor-positive axillary lymph nodes, tumor size less than or equal to 5 cm in diameter, and no invasion into skin or deep fascia. The primary surgical treatment was total mastectomy and lower axillary dissection. None of the patients received adjuvant therapy. Between 1977 and 1990, 7315 patients entered the study, and at the time of this analysis (January 1, 1990), the median follow-up time is 5 years. In univariate analyses, the following variables were significantly related to recurrence-free survival: age in premenopausal patients; tumor size; number of negative nodes removed; histological grade; and in premenopausal patients, estrogen receptor and progesterone (PgR) status. In multivariate analyses, age in premenopausal patients was the most important factor, followed by tumor size and histological grade, whereas PgR status in premenopausal patients was just of borderline significance. These variables should be included in multivariate analyses testing the value of more recently introduced prognostic factors.

Breast Neoplasms↗
PubMed1991

[Rationalization profits of radiographic diagnosis with systematic follow-up DBCG (Danish Breast Cancer Cooperative Group) programs. 1].

In the follow-up programme of the DBCG-77 control and treatment protocols for primary operable breast cancer, bone scintigraphy and chest X-ray were performed 6 months after surgery and thereafter yearly until the diagnosis of any recurrence or another cancer. In the present study, the value of the two examinations was examined to the 6th year control. As a result of a low incidence of primary recurrence to the bone (0.6-3.9%) and to the chest (0.0-3.0%) the value was found to be low. About two thirds of the patients with primary chest recurrence addressed themselves with or had at the time of control pulmonary symptoms. About one half of those patients, in whom (during a 12-month period after the scheduled bone scintigraphy) bone metastases were diagnosed by another method, had a normal scheduled bone scintigraphy. False positive changes were not infrequent, especially at the bone scintigraphies. The diagnosis of asymptomatic chest recurrence did not reduce the mortality among stage II patients, among whom the greatest value of the control examination was found. It is concluded, that systematic use of bone scintigraphy and chest X-ray is not justified in a follow-up programme for stage I and II breast cancer patients.

Bone and Bones↗
PubMed1991

[Prognosis after surgical treatment of breast cancer. 3. The low-risk group of the DBCG (Danish Breast Cancer Cooperative Group)].

The two therapeutic protocols of The Danish Breast Cancer Cooperative Group (DBCG) DBCG 77a (1977-1982) and 82a (1982-1990) comprise patients who were classified as low risk patients after operation for cancer of the breast, a total of 7,315 women. Treatment consisted of mastectomy and dissection of the lower and middle axillary levels. The median period of observation for DBCG 77a was 9 1/2 years and for DBCG 82a 3 1/3 years. The curves for recurrence-free survival and survival were found to be congruent in the two protocols. The recurrence-free survival after five years was 70% and 55% after ten years. Survival was 87% after five years and 70% after ten years. Local recurrence developed in 12.7% and 1.1% had distant recurrences simultaneously. Local recurrence was distributed with 60% in the scar or thoracic wall, 33% in the axilla and 7% in the clavicular lymph nodes. Distant recurrence alone developed in 11.4%. The time curves for development of local or distant recurrences were practically congruent. Local recurrence developed in 3.8% of the patients per annum during the first four years and after that in 1.5% per annum. Distant recurrence was found in 3.5% per annum in the first four years and after that in 1.8% per annum. The survival was significantly different after local and distant recurrence. Patients with tumours of grade 1 anaplasia had better prognoses than patient with grade 2 og 3 tumours as regards recurrence-free survival and survival. Multivariate analysis revealed that age under 40 years and anaplasia grad were significant prognostic variables for the parameters: distant recurrence and local recurrence. In addition, the number of lymph nodes in the operation specimen was a prognostic variable for local recurrence.

Adult↗
PubMed1991

[Adjuvant endocrine treatment of postmenopausal patients with breast cancer with high risk of recurrence. 5. Results from the DBCG (Danish Breast Cancer Cooperative Group) 77C randomized trial].

The role of antiestrogen treatment of postmenopausal breast cancer patients with high risk of recurrent disease is evaluated in a nationwide, prospective trial conducted by the Danish Breast Cancer Cooperative Group (DBCG). After total mastectomy and postoperative radiotherapy (RT), 840 patients were randomized to treatment with tamoxifen (RT + TAM) for one year, and 824 were randomized to no further therapy (RT). The recurrenceree survival (RFS) after ten years of lifeable analysis is 31% in the RT + TAM treated group, and 28% in the RT group (p = 0.01). Survival is 38% and 34% in the two treatment groups, respectively (p = 0.04). The data were further analyzed with respect to prognostic factors such as age, number of positive nodes, tumour size, and degree of anaplasia. Survival is prolonged in nearly all subgroups of patients treated with RT + TAM. However, the prolongation is only significant in patients with four or more positive nodes, with tumours of less than 5 centimeters or with tumours of anaplasia grade II. Estrogen (ER) and progesterone receptor (PgR) concentrations were measured in tumours from 309 and 219 patients, respectively. Only patients with ER and PgR values above 100 fmol/mg cytosol protein seemed to have a prolongation of survival. In conclusion, a modest survival benefit is achieved with one year of adjuvant tamoxifen treatment. Nevertheless, this is the first example of a systemic treatment approach being able to change the fatal course of breast cancer in postmenopausal patients. By means of endocrine therapy, and in the context of a new randomized trial, the DBCG will try to improve the survival in these patients even further.

Aged↗
PubMed1991

[Adjuvant chemotherapy in premenopausal and menopausal high-risk patients with breast cancer. 4. Results of the DBCG (Danish Breast Cancer Cooperative Group) 77B study].

From October 1977 to November 1982 premenopausal and menopausal high-risk breast cancer patients were included in a randomized trial (DBCG 77B). The primary surgical treatment was total mastectomy with axillary dissection. In the trial, a total of 1,034 patients were enrolled and received postoperative radiotherapy (RT) and were further randomized to 1) no systemic treatment, 2) cyclophosphamide, or 3) cyclophosphamide + methotrexate + 5-fluorouracil. The chemotherapy was given for one year. With a median observation time of ten years, the survival was 45, 60 and 62%, respectively. Retrospectively, the survival benefit was observed to be most pronounced in the age group less than 40 years, in patients with tumour size less than or equal to 5 cm or with less than or equal to 3 positive lymph nodes. In high-risk premenopausal and menopausal patients adjuvant chemotherapy combined with RT thus resulted in a more than 25% relative reduction in mortality at ten years of observation compared with RT alone.

Adult↗
PubMed1991

Tissue polypeptide antigen activity in cerebrospinal fluid: a marker of central nervous system metastases of breast cancer.

Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis, and 36 had no CNS involvement. The concentration of TPpA, which is a nonspecific marker for cell proliferation, was significantly higher in patients with CNS metastases than in those without it (P less than .0001; Mann-Whitney test). A tentative cutoff value for CNS metastases was set at 95 U/L TPpA; the upper limit of values indicating absence of CNS metastases was 89 U/L. Given these cutoff points, the sensitivity of TPpA as a marker for CNS metastases was 74% and the specificity was 100%; the predictive values of positive and negative tests were 100% and 86%, respectively. In 16 patients with CNS metastases, no correlation was found between TPpA activity in corresponding CSF and blood samples (correlation coefficient, Spearman's rho = .4; P greater than .1). In three patients treated for leptomeningeal carcinomatosis, the measurements of CSF TPpA showed correlation between the presence of tumor cells in the CSF and neurological clinical function. TPpA concentrations decreased in parallel with the clinical response and increased prior to CNS disease progression. As a marker for CNS metastases, the level of TPpA in the CSF in breast cancer patients appears to be superior to the level of protein, lactate dehydrogenase, or glucose, which showed very low sensitivity (41%, 47%, and 8%, respectively). For quantitative evaluation of treatment for leptomeningeal carcinomatosis, the TPpA level appears to be valuable and superior to CSF cytology, because tumor cells are not always present in CSF samples from patients with this condition.

Antigens, Neoplasm↗
PubMed1991

Phase II study of teniposide in adenocarcinoma of the lung.

A total of 26 evaluable patients with previously untreated, non-resectable adenocarcinoma of the lung were given 80 mg/m2 i.v. teniposide daily for 5 days every 3 weeks. Three partial responses (11%) were obtained that lasted for 12, 11 and 32 weeks, respectively. Leucopenia was the dose-limiting side effect, with WBC counts of less than 2 x 10(9)/l being observed in 42% of patients, resulting in one septic death. At the dose and schedule used in the present study, teniposide showed only limited activity in adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1991

Iron status markers in patients with small cell carcinoma of the lung. Relation to survival.

A longitudinal study of iron status markers (haemoglobin (Hb), serum (S-) iron, S-transferrin, transferrin saturation, S-ferritin) was performed in 31 chemotherapy treated patients with small cell lung cancer. At discovery, eight patients were anaemic (Hb less than 121 g l-1). Hb, S-iron and transferrin saturation were lower (P less than 0.01), and S-ferritin higher (P less than 0.01) than in healthy subjects. Chemotherapy induced an immediate fall in Hb (P less than 0.003), increase in S-iron (P less than 0.003) and transferrin saturation (P less than 0.001). Later in the disease a fall in S-transferrin (P less than 0.006) and an increase in S-ferritin (P less than 0.02) occurred. Thirty patients died during the 2 years observation. S-ferritin at discovery was correlated to performance status score (r = 0.57, P = 0.01) and to survival (r = -0.63, P less than 0.0002). Patients with S-ferritin less than or equal to 400 micrograms l-1 (n = 13) had longer survival than those with S-ferritin greater than 400 micrograms l-1 (n = 18) (P = 0.004).

Adult↗
PubMed1991

Combination chemotherapy of limited-stage small-cell lung cancer. A controlled trial on 221 patients comparing two alternating regimens.

The outcome of two different alternating regimens of chemotherapy was investigated in a prospective controlled trial in limited-stage small-cell lung cancer (SCLC). Both regimens comprised cyclophosphamide, lomustine, vincristine, methotrexate, doxorubicin and etoposide administered in different schedules. The investigative regimen (B) included simultaneous administration of cyclophosphamide + lomustine alternating with cyclophosphamide + doxorubicin, and with doxorubicin + lomustine. The hypothetical superiority of this regimen was based on data from experimental animal tumors suggesting potentiated efficacy of the three specific combinations. A total of 234 patients were included, and 113 vs 108 patients were eligible. Median survival in both groups was 48 weeks (p = 0.89). Complete remissions were observed in 36/101 and in 42/99 patients evaluable for response. There was no significant difference in response duration. At restaging after 18 months of chemotherapy 27 patients (16%) and 22 patients (16%), respectively, were free of disease. Six patients, three in each arm, are still alive, 8+ to 10.5+ years after diagnosis. Scheduled doses of the six agents were the same in the two regimens except for a 30% reduction of every second dose of cyclophosphamide in regimen B. Nevertheless, regimen B resulted in significantly more leukopenic patients, septicemic episodes, and blood transfusions, and the dosage of etoposide was more often reduced in arm B than in arm A. The increased toxicity was not associated with improved treatment results.

Adult↗