Search PubMed⌕ Search

Biomedical subjects

P Dombernowsky

Publications and source records attributed to P Dombernowsky.

At least 73 records · Page 4Linked to original sources
PubMed1995

Treatment of metastatic breast cancer with paclitaxel and doxorubicin.

The activity of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) against untreated and previously treated metastatic breast cancer (documented in anthracycline-resistant disease and in extensively pretreated patients as well) has prompted investigations of the optimal doses and schedules of paclitaxel/doxorubicin combinations. With one exception, paclitaxel has been administered in either a 24- or a 3-hour infusion, while the administration times for doxorubicin vary from bolus injection to a 72-hour infusion. Results of these completed phase I and II trials are reviewed. Also reported are two ongoing European trials that have achieved promising preliminary results. In Milan, a phase I trial has achieved a preliminary response rate exceeding 90% in 30 chemotherapy-naive patients treated with an alternating schedule of paclitaxel over 3 hours and intravenous bolus doxorubicin. At doses of paclitaxel 200 mg/m2 and doxorubicin 60 mg/m2, the dose-limiting toxicity is leukopenia and mucositis. Furthermore, congestive heart failure has occurred in six patients. We are conducting a phase I/II study in minimally pretreated patients, with a 30-minute doxorubicin infusion preceding a 3-hour paclitaxel infusion every 3 weeks. Of 24 patients evaluable for response, five have achieved partial responses and three complete responses. (Another five partial and two complete responses need confirmation.) Of the two dose levels now given, all responses occurred at the higher paclitaxel/doxorubicin level, 175 and 60 mg/m2, respectively. Despite grades 3 and 4 neutropenia in 31% and 60% of courses, respectively, only six patients have been hospitalized for febrile neutropenia. Of concern, the left ventricular ejection fraction has decreased to below normal in six patients and two have developed symptomatic congestive heart failure. Whether lowering the peak doxorubicin concentration will preclude this effect, which has been observed only in the studies using short infusions of both drugs, is under investigation.

Antibiotics, Antineoplastic↗
PubMed1994

[Treatment of drug-induced nausea and vomiting].

Patients consider nausea (N) and vomiting (V) as severe adverse events to chemotherapy (CT). The introduction of the 5-HT3 antagonists have added a new dimension to the treatment of acute N and V. A review of the pathophysiology of N and V induced by CT and of the prescription of antiemetics used in Denmark is given. Dopamine D2 antagonists such as metoclopramide and metopimazine have a moderate antiemetic effect, when given in conventional low doses. A combination of one of these drugs and a steroid is recommended as first choice in patients receiving moderately emetogenic CT. In severe emetogenic CT, especially cisplatin-based, the 5-HT3 antagonists have resulted in a significant improvement and ondansetron, granisetron or tropisetron are in these patients recommended as first choice, either given alone or in combination with steroids. The duration of such a treatment should be restricted to the first 24 hrs after CT, as none of these expensive drugs seem to improve treatment of delayed emesis. The best known treatment of delayed emesis is the combination of a dopamine D2 antagonist and a steroid. Many pathophysiological and clinical questions are unanswered. Future trials using correct methodology should focus on patients receiving multiple-day CT, patients receiving multiple cycles of CT and on patients resistant to first-line antiemetic treatment.

Antiemetics↗
PubMed1994

Sex hormone levels in postmenopausal women with advanced metastatic breast cancer treated with CGS 169 49A.

30 postmenopausal patients with metastatic breast cancer were treated with three different doses of fadrozole hydrochloride (CGS 169 49A), a non-steroidal competitive aromatase inhibitor. The effect of 0.5, 1 and 2 mg given twice daily upon the levels of oestrogens, their androgen precursors and upon the concentration of sex hormone binding globulin (SHBG) was investigated after 1 and 3 months and then every 3 months until progression of disease. A significant reduction in the serum concentration of oestrone (P < 0.0001) was obtained at all doses. Also, the serum concentration of oestrone sulphate was significantly reduced (P < 0.0001). However, after 1 month, the concentration was significantly different from pretreatment levels (P < 0.01) only at the 4 mg daily dose. A decline was also observed in the concentration of SHBG (P < 0.05), with a concomitant elevation of the percentage non-SHBG-bound oestradiol. The androgens, testosterone and dehydroepiandrosterone sulphate, were unaltered during treatment, while androstendione was significantly elevated at the 2 mg daily dose (P < 0.001).

Aged↗
PubMed1994

Fucosyl-GM1 in small-cell lung cancer. A comparison with the tumour marker neuron-specific enolase.

BACKGROUND: Recently, the ganglioside Fucosyl-GM1 (FucGM1) has been described as a possible new tumour marker for small-cell lung cancer (SCLC). FucGM1 has been detected in 75% to 90% of SCLC tumours by immunohistochemical analysis and in about 50% of sera from SCLC patients. Neuron-specific enolase (NSE) is a glycolytic enzyme which is expressed in the majority of SCLC tumours and patient sera. PATIENTS AND METHODS: Sera from 156 patients with SCLC were analyzed for FucGM1 with a scintillation proximity assay (SPA), which is a simple and sensitive analysis. Sera were analyzed before the initiation of chemotherapy, and twenty patients were monitored during and after treatment. The concentration of FucGM1 was compared to the tumour marker NSE and related to clinical data and survival. RESULTS: Sixty-three per cent of the patients were positive for FucGM1. The concentrations did not correlate with NSE or clinical data including stage of disease, organ site of metastases or ABO blood group status. Nor did the expression of FucGM1 correlate with survival. As a monitor of clinical response, a correlation was found in 8 out of 20 patients. Eighty-four per cent of the patients were positive for NSE; and 97% were positive for either FucGM1 or NSE. CONCLUSION: We conclude that FucGM1 does not have a clinical role as a tumour marker for patients with SCLC at diagnosis or during treatment.

Adult↗
PubMed1993

Ondansetron plus metopimazine compared with ondansetron alone in patients receiving moderately emetogenic chemotherapy.

BACKGROUND AND METHODS: The serotonin (5-hydroxytryptamine3) antagonists have improved the treatment of acute chemotherapy-induced nausea and vomiting, but their ability to prevent delayed nausea and vomiting seems less pronounced. The results of a preliminary open trial suggested that the addition of a selective dopamine D2 antagonist could improve the antiemetic efficacy of the serotonin antagonists. In a randomized, double-blind, crossover trial, we compared oral treatment with ondansetron (8 mg twice a day) and the dopamine D2 antagonist metopimazine (30 mg four times a day) with treatment with ondansetron alone for three days in 30 patients who had vomited during the previous cycle of chemotherapy. All the patients received moderately emetogenic chemotherapy. RESULTS: Combination treatment with ondansetron and metopimazine significantly reduced the incidence of acute (P = 0.006) and delayed (P = 0.02) nausea and acute (P = 0.02) and delayed (P = 0.006) vomiting, as compared with treatment with ondansetron alone. Patients had significantly fewer days of nausea (P = 0.03) and vomiting (P = 0.003) if they received combination therapy. Sixty-seven percent of the patients preferred ondansetron and metopimazine, and 33 percent favored ondansetron alone (P = 0.10). Adverse reactions were mild with both regimens. With the exception of constipation, which was reported more frequently with combination therapy (P = 0.03), there were no significant differences in adverse reactions. CONCLUSIONS: Ondansetron plus metopimazine is a highly effective and safe antiemetic regimen that is markedly superior to treatment with ondansetron alone in patients receiving moderately emetogenic chemotherapy.

Adult↗
PubMed1993

[The value of bone marrow scintigraphy in patients with recurrent breast cancer].

Attempts were made to assess the value of various methods of demonstration of bone metastases in patients with recurrence of cancer of the breast. A material of 123 patients with suspected or verified recurrence of cancer of the breast was submitted to a programme of investigation consisting of conventional X-ray survey of the axial skeleton and thorax, bone tissue scintigraphy, bone marrow scintigraphy, bone biopsy and aspiration of marrow and blood status including serum alkaline phosphatase. 54% and 29% of the patients had bone, metastases as assessed radiographically and by biopsy, respectively. In patients with radiographically demonstrated bone metastases, the predictive value of positive (PV-pos) whole-body scintigraphy was 79%. The findings on bone tissue scintigraphy and bone marrow scintigraphy were in agreement with the radiographic findings in 78% and 72%, respectively, and with the biopsy findings in 71% and 74%, respectively, of the cases. All of the cases of metastases verified by biopsy were identified also by radiographic examination and by bone tissue scintigraphy. The predictive value of negative bone tissue scintigraphy (PV-neg) was 76% and of bone marrow scintigraphy 65%. With biopsy as the final proof, bone tissue scintigraphy, bone marrow scintigraphy and radiography were found to have PV-pos values of 96%, 89% and 95%, respectively and PV-neg values of approximately 50% for all three forms of examination. Bone marrow scintigraphy has thus no diagnostic advantages as compared with bone tissue scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗
PubMed1993

Toremifene and tamoxifen in advanced breast cancer--a double-blind cross-over trial.

Toremifene (TOR) is a triphenylethylene derivative related to tamoxifen (TAM). TOR has antitumor activity, not dependent on estrogen receptors, and responses with TOR have been observed in patients with progressive disease during TAM-treatment. To elucidate possible cross-resistance between these two antiestrogens, we compared their anti-tumor activity in a randomized, double-blind, cross-over study. 66 postmenopausal women with advanced estrogen receptor positive or unknown breast cancer and a median age of 63 years (range 38-82) were included. Patients were randomized to TAM 40 mg/day or TOR 240 mg/day. Treatment continued until progressive disease, when cross-over to the alternative treatment was done. The response rate with first line TOR was 29% (95% confidence limits 10-41%) and with TAM 42% (95% confidence limits 25-61%). Response rates and response durations, survival and toxicity were not significantly different between the two treatments. 44 patients progressing on first line TAM or TOR were evaluable for second line TOR or TAM treatment. As no responses were observed, the possibility of over-looking a response rate of 20% or more is less than 1%. In conclusion, this study strongly indicates that TOR and TAM are clinically cross-resistant in patients with advanced breast cancer.

Adult↗
PubMed1993

Phase II study of 4'-iodo-4'-deoxydoxorubicin in non-resectable non-small-cell lung cancer.

A total of 44 patients with previously untreated; non-resectable non-small-cell lung cancer (NSCLC) were treated with 4'-iodo-4'-deoxydoxorubicin (IDX), which is an analogue of doxorubicin with less cardiotoxicity. Patients received 80 mg/m2 i.v. every 3 weeks. Dose reductions were carried out for haematological toxicity. Response was assessed prior to each treatment according to WHO criteria. Among the 43 evaluable patients, 1 (2%; 95% confidence limits, 0-8%) achieved a partial response. Leucocytopenia of WHO grade 3 or 4 occurred in 64% of patients and corresponding thrombocytopenia grade 3 or 4 occurred in 30%. Of the 26 patients who were evaluated by measurements of the left ventricular ejection fraction (LVEF), 4 had a decline in LVEF of more than 15%, and 2 patients developed congestive heart failure. Myocardial biopsies were not done. In conclusion, IDX is not active in NSCLC at the applied dose and on the schedule used. Moreover, it does not seem possible to increase the dose intensity further due to the observed toxicity.

Carcinoma, Non-Small-Cell Lung↗
PubMed1993

Ceftriaxone versus latamoxef in febrile neutropenic patients: empirical monotherapy in patients with solid tumours.

121 patients with 132 febrile episodes were randomised to ceftriaxone or latamoxef monotherapy in order to compare antibiotic efficacy in neutropenic patients treated with cytotoxic chemotherapy for solid tumours. In 80 evaluable episodes no significant differences were observed between the two groups with respect to efficacy and fatal failure rates. Of episodes treated with ceftriaxone, 67% showed a favourable clinical response vs. 61% in the latamoxef group. The clinical response rates in episodes with documented bacterial infections were 67 and 56% in the two treatment groups. In 18% of the episodes with documented initial infections the patients died of presumably uncontrolled infection. The convenient once daily dosage schedule combined with fewer severe adverse reactions favours the use of ceftriaxone instead of latamoxef. Although a relative high degree of response was seen, empirical antibiotic monotherapy apparently does not offer a sufficient antibacterial cover in infections in this type of patient with defective host immunity.

Adult↗
PubMed1993

The diagnostic and prognostic value of serum bone Gla protein (osteocalcin) in patients with recurrent breast cancer.

Serum bone Gla protein (S-BGP), a marker of bone metabolism, was measured in 60 patients included in a staging programme for recurrent breast cancer. Other diagnostic procedures comprised S-alkaline phosphatase (S-AP), bone scan (B-scan), bilateral iliac crest bone marrow biopsies, and radiological bone survey. The sites of recurrence were bone (61%), bone marrow (46%), soft tissue (52%), lung (13%), pleura (11%), liver (4%), and brain (2%). Radiology and bone biopsy served as key diagnoses as to the presence or absence of bone metastases. The diagnostic efficiency of B-scan and S-AP was greater than that of S-BGP, and the result of BGP measurement was associated with neither extent nor number of bone metastases. However, the BGP values were significantly lower in patients who had visceral metastases, and the median duration of survival after recurrence was 13 months for patients with low S-BGP levels (= < 2.0 nmol l-1), compared to 18 months for patients with medium S-BGP values (2.0-2.9 nmol l-1), and 25 months for patients with high values (> 3.0 nmol l-1) (p = 0.19). Analyses of the simultaneous effect of univariate prognostic factors were performed using the Cox proportional hazards model. S-alkaline phosphatase (S-AP) and S-BGP were the only significant, independent prognostic factors.

Adult↗
PubMed1993

A novel method for monitoring high-risk breast cancer with tumor markers: CA 15.3 compared to CEA and TPA.

BACKGROUND: An early and reliable diagnosis of metastatic spread has increased interest in serum tumor markers. This study investigated the ability of CA 15.3, CEA, and TPA to identify, predict, and exclude metastases in bone/viscera during adjuvant treatment and follow-up of high-risk breast cancer. METHODS: Ninety females with high-risk breast cancer were included in the study. Response evaluation was based upon clinical examination, x-rays or histology and elaborated marker criteria. RESULTS: During the marker monitoring period, metastases in four patients were confined to skin or lymph nodes, 21 developed metastases to bone/viscera, and 65 females had no evidence of metastases. CA 15.3, CEA, and TPA correctly classified 48%, 10%, and 19% of the patients with metastases in bone/viscera, and 100%, 94%, and 98% without. Following CA 15.3, CEA, and TPA recurrence, 100%, 33%, and 60% of the patients developed metastases in bone/viscera. Metastases in bone/viscera were excluded in 86%, 76%, and 79% of patients without CA 15.3, CEA, and TPA recurrence. CONCLUSION: Only CA 15.3 gave reliable information about recurrence. Metastases in bone/viscera were identified in 10 of the 21 patients with CA 15.3. There was no false-positive CA 15.3 information on the 65 patients without clinical recurrence. The PVneg (86%) indicated that when CA 15.3 did not signal recurrence, metastases to bone/viscera were not likely.

Adult↗
PubMed1993

Prognostic value of serum tetranectin in patients with metastatic breast cancer.

To evaluate serum tetranectin as a prognostic marker before first-line chemotherapy, serum levels were studied in 67 patients with metastatic breast cancer. In the Cox analyses, the relative risk (RR) for death of cancer varied with the cut-off level of serum tetranectin. A maximal RR of 5.0 was found for patients with serum tetranectin < or = 5.4 mg/l. The maximal RR of death for the other prognostic variables were multiple metastases 2.8, and for a poor performance status 2.0. Testing for the outcome, progressive disease, a maximal RR of 3.8 was found for patients with serum tetranectin < or = 5.3 mg/l, a maximal RR of 3.7 for multiple metastases and a maximal RR of 1.8 for a poor performance status. Significantly lower serum tetranectin values were found in patients with a poor treatment response compared to well responding patients. Serum tetranectrin seems to be useful as an additional prognostic factor in metastatic breast cancer.

Adult↗
PubMed1993

Interpretation of results for tumor markers on the basis of analytical imprecision and biological variation.

Interpretation of results for CA 15.3, carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) during breast cancer monitoring requires data on intra- (CVP) and inter- (CVG) individual biological variation, analytical imprecision (CVA), and indices of individuality. The average CVP and CVG obtained from 22 healthy women were, respectively, 6.2% and 62.9% (CA 15.3), 9.3% and 86.8% (CEA), and 28.3% and 133% (TPA). The indices of individuality were all < 0.6: 0.2 (CA 15.3), 0.15 (CEA), and 0.2 (TPA). CVA depended on the concentration of the analytes. CVP and CVA determine what constitutes a significant difference between sequential results. Assuming a CVA of 11.2% (CA 15.3), 9.5% (CEA), or 11.9% (TPA), results must differ by 30%, 31%, or 72%, respectively, for P < or = 0.05. We found that CVP and CVA contribute considerably to the variation during breast cancer monitoring. Consequently, both CVP and CVA should be considered in criteria for marker evaluation. Because of low indices of individuality, conventional cutoff limits are inappropriate both for initial identification and for follow-up of breast cancer.

Adult↗
PubMed1993

Cyclophosphamide versus ifosfamide: a randomized phase II trial in adult soft-tissue sarcomas. The European Organization for Research and Treatment of Cancer [EORTC], Soft Tissue and Bone Sarcoma Group.

Ifosfamide (5 g/m2) was compared with its parent analogue cyclophosphamide (1.5 g/m2) in a randomized phase II study. Both drugs were given by 24-h intravenous (i.v.) infusion every 3 weeks along with i.v. bolus infusions of mesna (400 mg/m2), which was given every 4 h for nine administrations. Eligibility criteria included an age of 15-75 years, biopsy-proven advanced metastatic soft-tissue sarcoma, and a World Health Organization performance status of 0-2. Exclusion criteria were prior treatment with classic alkylating agents, a creatinine level of > 150 mumol/l, a bilirubin level of > 20 mumol/l, a leukocyte cell count of < 3.5 x 10(9)/l, and a platelet count of < 100 x 10(9)/l. A total of 171 patients were entered, 24 of whom were ineligible and 12, inevaluable, leaving 135 patients evaluable. In all, 67 patients were treated with cyclophosphamide, and the overall response rate was 7.5%. All responders to cyclophosphamide were patients who had not received prior chemotherapy (13% of 38 patients). Another 68 patients were given ifosfamide, 18% of whom responded to treatment. Of the 28 ifosfamide-treated patients who had received prior chemotherapy, 7% were responders. The response rate for the remaining 40 patients was 25%. The higher overall response rate (P = 0.13) obtained with less myelosuppression in ifosfamide-treated patients suggests that this agent may have advantages over cyclophosphamide in combination therapy.

Adolescent↗
PubMed1993

Ifosfamide plus doxorubicin in previously untreated patients with advanced soft-tissue sarcoma.

The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft-tissue sarcoma. Treatment consisted of an intravenous bolus injection of doxorubicin at a dose of 50 mg/m2 followed by a 24-h infusion of ifosfamide at 5 g/m2 plus mesna, with therapy being repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of the 203 patients entered, 175 were evaluable for response. The overall response rate was 35% (95% confidence interval, 28%-42%), with 9% of patients achieving complete responses and 26% showing partial responses. The median time to progression was 29 weeks for all evaluable patients and 67, 40, and 28 weeks for complete and partial responders and patients with stable disease, respectively. The median duration of survival was 58 weeks. Myelosuppression was the dose-limiting toxicity, resulting in leukopenia (World Health Organization grades 3 and 4) in 73% of the evaluable patients. Other side effects were rare and usually well manageable.

Adolescent↗