Epirubicin and cyclophosphamide versus epirubicin and docetaxel as first-line therapy for women with metastatic breast cancer: final results of a randomised phase III trial.

BACKGROUND: This randomised phase III trial was carried out to compare the efficacy and safety of epirubicin and cyclophosphamide (EC) with epirubicin and docetaxel (Taxotere) (ED) as first-line chemotherapy for metastatic breast cancer. PATIENTS AND METHODS: Patients (n = 240) were randomly assigned to receive either ED (epirubicin 75 mg/m(2) and docetaxel 75 mg/m(2)) or EC (epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2)). The primary end point was objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: ORR for patients randomly assigned to receive EC and ED were 42% and 47%, respectively (P = 0.63). Median PFS [10.1 versus 10.3 months; hazard ratio (HR) 0.98; log-rank P = 0.38] and OS (19.9 versus 30.0 months; HR 0.663; log-rank P = 0.21) were comparable in both arms. Although grade 3/4 leucopenia occurred more frequently with ED (81% versus 73%; P = 0.01), there were no significant differences in the incidence of febrile neutropenia and grade 3/4 infections. Grade 3/4 non-haematologic toxicity was infrequent in both arms. Congestive heart failure was observed in one patient in each arm. CONCLUSION: In this randomised trial, no differences in the efficacy study end points were observed between the two treatment arms.

Gemcitabine and carboplatin in intensively pretreated patients with metastatic breast cancer.

BACKGROUND: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. PATIENTS AND METHODS: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. RESULTS: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombocytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. CONCLUSION: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2).

The clinical benefit of pegylated liposomal doxorubicin in patients with metastatic breast cancer previously treated with conventional anthracyclines: a multicentre phase II trial.

This study evaluates the clinical benefit of pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC), previously treated with conventional anthracyclines. Seventy-nine women with MBC previously treated with anthracyclines received PLD 50 mg m(-2) every 4 weeks. All patients were previously treated with chemotherapy and 30% of patients had > or =3 prior chemotherapies for metastatic disease. Patients were considered anthracycline resistant when they had disease progression on anthracycline therapy for MBC or within 6 months of adjuvant therapy. The overall clinical benefit rate (objective response+stable disease > or =24 weeks) was 24% (16.1% in patients with documented anthracycline resistance vs 29% in patients classified as having non-anthracycline-resistant disease). There was no difference with respect to the clinical benefit between patients who received PLD >12 months and those who received PLD < or =12 months since last anthracycline treatment for metastatic disease (clinical benefit 25 vs 24.1%, respectively). Median time to progression and overall survival were 3.6 and 12.3 months, respectively. The median duration of response was 12 months, and the median time to progression in patients with stable disease (any) was 9.5 months. Fourteen patients (17.7%) had a prolonged clinical benefit lasting > or =12 months. In conclusion, PLD was associated with an evident clinical benefit in anthracycline-pretreated patients with MBC.

Randomised trial: survival benefit and safety of adjuvant dose-dense chemotherapy for node-positive breast cancer.

We evaluated the survival benefit, safety, feasibility, and tolerability of dose-dense (DD) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer. Randomised patients (n=216) received DD or conventional-schedule (CS) chemotherapy. Dose-dense regimen patients (n=108) received epirubicin 90 mg m-2 plus paclitaxel 175 mg m-2 in four 14-day cycles, then cyclophosphamide 600 mg m-2, methotrexate 40 mg m-2, and fluorouracil 600 mg m-2 (CMF 600/40/600) in three 14-day cycles, plus filgrastim 5 microg kg day-1 as growth support in every cycle. Conventional-schedule regimen patients (n=108) received epirubicin 90 mg m-2 plus cyclophosphamide 600 mg m-2 in four 21-day cycles, then CMF 600/40/600 in three 21-day cycles, plus filgrastim if required. After a median follow-up of 38.4 months, 71 patients (33%) relapsed or died: DD, 33 patients (15 deaths); CS, 38 patients (22 deaths). Dose dense showed a trend for improved disease-free survival (DFS) and overall survival (OS). Four-year rates of DFS and OS were 64 and 85% for DD, and 58 and 75% for CS. All seven cycles were administered to 208 patients (96%). Rates of cycle delay, discontinuation, dose reduction, and adverse events were similar in both groups. Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF, supported by filgrastim, is safe and improves survival for patients with node-positive breast cancer.

First-line gemcitabine versus epirubicin in postmenopausal women aged 60 or older with metastatic breast cancer: a multicenter, randomized, phase III study.

BACKGROUND: This randomized, phase III study compared the efficacy and safety of first-line gemcitabine versus epirubicin in the treatment of postmenopausal women with metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients aged > or = 60 years (median 68 years) with clinically measurable MBC received either gemcitabine 1200 mg/m(2) or epirubicin 35 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. RESULTS: Of 410 patients entered, 397 (198 gemcitabine and 199 epirubicin) were randomized and qualified for the time to progressive disease (TTP) and survival analyses. Total cycles administered in 185 gemcitabine and 192 epirubicin patients, respectively, were 699 (mean 3.5, range 0-12) and 917 (mean 4.6, range 0-10). Epirubicin demonstrated statistically significant superiority in TTP (6.1 and 3.4 months, P=0.0001), overall survival (19.1 and 11.8 months, P=0.0004), and independently assessed response rate (40.3% and 16.4% in 186 and 183 evaluable patients, P <0.001). For gemcitabine (n=190) and epirubicin (n=192), respectively, common WHO grade 3/4 toxicities were neutropenia (25.3% and 17.9%) and leukopenia (14.3% and 19.3%). Of the 28 on-study deaths (17 gemcitabine, 11 epirubicin), three were considered possibly or probably related to treatment (gemcitabine). CONCLUSIONS: Postmenopausal women > or =60 years of age with MBC tolerate chemotherapy well. In this study, epirubicin was superior to gemcitabine in the treatment of MBC in women age > or =60, confirming that anthracyclines remain important drugs for first-line treatment of MBC.

Primary chemotherapy with doxorubicin and paclitaxel in patients with early breast cancer: final results of a multicenter phase II study.

PURPOSE: To assess the efficacy and safety of primary systemic treatment with doxorubicin and paclitaxel in patients with early breast cancer. PATIENTS AND METHODS: Forty patients with newly diagnosed, histologically confirmed breast cancer (T2, N0-1, M0) received primary chemotherapy with doxorubicin (60 mg/m2) and paclitaxel (200 mg/m2) in 3-week intervals for up to four courses. RESULTS: A total of 151 cycles were administered. The clinical response rate as assessed by sonographic measurement was 70%, and complete remissions of the primary tumor occurred in two patients. Eight patients (20%) had histologically confirmed complete responses. Predominant toxicity was myelosuppression with grade 3/4 neutropenia in 70% of patients. Non-hematological toxicity was generally moderate. Grade 4 non-hematological toxicities were not observed and grade 3 toxicity was reported with alopecia (98%) and stomatitis (10%). CONCLUSIONS: The combination of doxorubicin and paclitaxel is safe and highly active in patients with early breast cancer. The evaluated schedule is suitable for phase III studies.

Adjuvant treatment of breast cancer patients with 1-3 positive lymph nodes: vinorelbine plus epirubicin; vinorelbine plus epirubicin sequential followed up by paclitaxel; epirubicin plus cyclophosphamide; epirubicin plus cyclophosphamide sequential followed up by paclitaxel. A phase II study.

PURPOSE: The efficacy of anthracyclin-containing adjuvant chemotherapy of node-positive breast cancer can be further improved by adding sequential paclitaxel (T). There is also clinical evidence that replacing cyclophosphamide (C) with vinorelbin (V) might further reduce toxicity. In order to assess the safety of these options, we initiated a clinical cohort study of epirubicin/cyclophoshamide and epirubicin/vinorelbine with or without sequential paclitaxel. METHOD: Patients with node-positive (1-3) breast cancer were assigned to open-label epirubicin/vinorelbine (EV), epirubicin/vino-relbine and sequential paclitaxel (EV/T), epirubicin/cyclophosphamide (EC) or epirubicin/cyclophosphamide plus sequential paclitaxel (EC/T) therapy. RESULTS: Fifty four outpatients received a total of 304 chemotherapy cycles. There were significant differences in grade III/IV anemia only between the EV/T and EC/T groups, in favor of the EC/T group (P=0.002). CONCLUSIONS: The safety of paclitaxel is not impaired when given sequentially after administration of the two anthracyclin-containing regimens. The exchange of cyclophosphamide against vinorelbine leads to deteriorating safety of the EC/T regimen.

Gemcitabine combined with cisplatin as first-line treatment in patients 60 years or older with epithelial ovarian cancer: a phase II study.

This phase II study evaluated the activity and toxicity of gemcitabine plus cisplatin as first-line treatment of patients with advanced ovarian cancer. Chemonaive patients >/=60-year-old with FIGO stage IIIC or IV epithelial ovarian carcinoma were enrolled. Patients received cisplatin 75 mg /m2 on day 1 and gemcitabine 1250 mg /m2 on day 1 (before cisplatin) and day 8 of a 21-day cycle. Of 44 female patients (median age, 70 years), 72.7% had stage IIIC disease and 67.4% had a Karnofsky performance status >/=80. Of the 37 response-evaluable patients (35 with measurable lesion[s] >/=2 cm), there were seven (18.9%) pathologic complete responses, two (5.4%) pathologic partial responses, two (5.4%) clinical complete responses, and 12 (32.4%) clinical partial responses, for an overall response rate of 62.2% (95% CI, 44.8%-77.5%), and a pathologic response rate of 24.3% (95% CI, 11.8%-41.2%). Median survival was 27.7 months (95% CI, 14.3-40.8 months). Grade 3/4 neutropenia and thrombocytopenia occurred in 59.5% and 30.2% of patients, respectively, with neutropenic fever in one patient. Grade 3 nausea /vomiting and alopecia occurred in 25.6% and 9.5% of patients, respectively. We conclude that gemcitabine plus cisplatin is active and feasible as first-line treatment of advanced epithelial ovarian cancer in patients >/=60 years. Further clinical trials adding gemcitabine to current standard, first-line treatment seem warranted in younger as well as older patients.

Necrotizing small-vessel vasculitis confined to the uterine cervix.

OBJECTIVES: To report our experience with five cases of apparently isolated small-vessel vasculitis of the uterine cervix. METHODS: Case study of five patients with necrotizing vasculitis discovered incidentally in surgical specimens of the female genital tract, and a review of the pertinent literature on this subject. RESULTS: All patients lacked clinical and serological features of the well-delineated vasculitic syndromes. Comprehensive workup failed to yield any evidence of an underlying disorder. All patients were managed expectantly and did not develop systemic vasculitis during follow-up ranging from 6 months to 5 years. CONCLUSIONS: Isolated vasculitis of the female genital tract can be encountered as an innocuous finding in otherwise healthy individuals. The cause and pathogenesis of this disorder remain obscure. Rheumatologists should be familiar with this rare and vexing form of vasculitis and with its benign prognosis.

Entbindungsmodus und Neonatalzustand in Abhangigkeit vom Gestationsalter bei Geburten aus Beckenendlage.

OBJECTIVE: The objective of this retrospective analysis was to compare the obstetrical procedures at premature birth and delivery at term. The aim was to show the influence of gestational time on mode of delivery and neonatal state. MATERIAL AND METHODS: 339 births from breech presentation between 1988-1990 were compared with premature births and deliveries at term. RESULTS: Frequency of breech presentation totalled 4.1%. 173 deliveries (51.7%) resulted vaginally, 26 cases (7.8%) with freeing of arms and 4 cases (1.2%) as extraction. Frequency of cesarean sections totalled 48.3%. The number of premature births reached in the group of breech presentation 23.1%. Births at term resulted with 58% predominantly vaginally (abdominally in 42%). Between the 31st and 36th gestational week the number of cesarean sections rose to 67.3%, in the 31st week it even reached 78.9%. The neonatal state was described with the help of Apgar-scores and umbilical cord-pH-values. The share of newborns with optimal Apgar-values after 1 minute (8-10) was in premature births with 36.5% only about half as large as in deliveries at term (77.6%). Only 9.6% of the children showed pH-values below 7.20. Number of newborns with these pH-values totalled in premature births in the 31st week 35.3%, for terms between the 31st and 36th week 15.6%, and declined in mature births to only 6.2%. CONCLUSIONS: Estimating the neonatal state of the group of breech presentations the vaginal birth should keep an equal rank in the delivery plan of a clinic. At the appraisal of the childlike early morbidity of a delivery group the number of premature newborns is decisive.

Controlled multicentre study of the influence of subcutaneous recombinant human erythropoietin on anaemia and transfusion dependency in patients with ovarian carcinoma treated with platinum-based chemotherapy.

This randomised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin (rhEPO) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy. The patients were randomly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously, three times a week, or open control. Patients also received up to 6 cycles of carboplatin or cisplatin, alone or in combination with other cytotoxic agents. Intention-to-treat analysis showed that 39.4% of patients in the control group received at least one blood transfusion, compared with 9.2% of patients treated with rhEPO. Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels < 10 g/dl (P < 0.001 and < 0.05, respectively). A haemoglobin decrease < 1 g/dl during the first chemotherapy cycle, as well as a low baseline serum erythropoietin concentration, predicted a low transfusion need in rhEPO-treated patients but not in controls. During the study, 103 patients suffered at least one adverse event, but no serious, and only nine non-serious adverse events were considered possibly related to rhEPO therapy. These results indicate that treatment with rhEPO prevents anaemia, it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy, and it is well tolerated. A starting dose of 150 U/kg of rhEPO, three times a week, may be recommended.

[Prognostic factors and results of treatment in endometrial carcinoma]. / Prognosefaktoren und Behandlungsergebnisse beim Endometriumkarzinom.

158 patients with endometrial cancer who were treated between 1980-1990 at the Department of Obstetrics and Gynecology, Hospital Berlin-Buch, were reviewed retrospectively with regard to prognostical and therapeutical aspects. The 5-year-survival rate of all patients amounted to 84%. The 5-year-survivals were 92.6% for stage I, 87.5% for stage II and 47.6% for stage III (old FIGO classification). Depth of myometrial invasion, lymph-vascular space involvement, lymph-nodal status, tumor type and grading are of dominant prognostic value. Surgery was the treatment of choice in all reviewed cases. No statistically significant difference was observed in the 5-year survival rate between vaginal and abdominal hysterectomy. The 5-year survival rate for cases with vaginal hysterectomy was 85.4% and for abdominal hysterectomy 87.8%.

[Evaluation of epidemiologic risk factors for endometrial carcinoma based on a case-control study]. / Wertung von epidemiologischen Risikofaktoren für das Endometriumkarzinom auf der Basis einer Fall-Kontroll-Studie.

In a case-control-study an epidemiological investigation of cancer of the endometrium was carried out. The study included 159 cases and 159 controls. It was shown, that woman in the sixth life decade with overweight, a smaller number of deliveries and a later menopause had a higher risk for endometrial cancer. Other risk factors are diabetes mellitus and hypertension. But it is necessary to see the relationship between the typical age for these two characteristics and the typical age for endometrial cancer. The intake of estrogens without enough gestagens during an estrogen replacement therapy was associated with an increased risk. Furthermore the patients with carcinoma of the uterine corpus had a higher incidence of malignant tumors in their families and more breast cancer in their own case history. A history of oral contraceptive use appeared to reduce the risk of endometrial cancer. In addition there is an negative association between smoking and endometrial cancer. Thus factors of high risk related to cancer of the endometrium could be defined. Preventive examinations of high risk groups could help to decrease the incidence of endometrial cancer.

[Fathers in the delivery room--an East/West comparison]. / Väter im Kreisssaal--ein Ost/West-Vergleich.

The attendance of fathers in the delivery room to accompany the women giving birth is in Germany quite common. In this study we wanted to compare the results of a questionnaire on feelings, intention an anxiety of attending fathers in an east and west German maternity hospital. Although social acceptance of fathers in the delivery room in the eastern part of Germany is delayed by 10 years (compared to western clinics) the over all impression of attending fathers was similar. We aid find differences concerning the expectations, the way of mental preparing and considerations participating the approaching birth in east and west questionared fathers. The results also showed variable knowledge in respect of pregnancy and birth. We do think that after a time of ("father") experience in the east part of Germany the expression of opinion will adjust.

[Effectiveness of cisplatin alone and in combination within the scope of primary therapy of ovarian cancer. Results of a prospective multicenter study]. / Die Effektivität von Cisplatin allein und in Kombination im Rahmen der Primärtherapie des Ovarialkarzinoms. Ergebnisse einer prospektiven Multizenterstudie.

The efficiency of cis Platin (DDP) alone and in combination with Adriamycine (ADM) and Cyclophosphamid (CTX) were evaluated in a prospective randomized trial containing 173 pat. suffering from advanced ovarian cancer (FIGO III/IV). Therapeutic schedule and results: (table; see text) The most side effects concerned vomiting (WHO Grad 2) in 90%, nausea (WHO Grad 2) in 95% and alopecia in 50% out of all pat.

[C-reactive protein in the maternal serum and risk of maternal infection in premature rupture of the fetal membranes and threatened premature labor]. / C-reaktives Protein (CRP) im mütterlichen Serum und mütterliches Infektionsrisiko bei vorzeitigem Blasensprung und drohender Frühgeburt.

For diagnosis of ascending intra-uterine infections, regular controls of the serum CRP levels were carried out in 129 patients with premature rupture of membranes and impending premature labour. The height of the maternal CRP level and the simultaneously determined leucocyte counts and band counts were compared with the peripartal fever morbidity (intrapartal fever, puerperal fever). It was established that patients who had a prepartal CRP level of 10 mg/l or more suffered febrile complications more frequently (fever morbidity 18.2%) than females in whom such high CRP values did not occur (fever morbidity 3.4%). Similar correlations existed between the other parameters tested and the fever morbidity, and subclinical intrauterine infections were recognized with higher reliability if CRP, leucocyte count and band count had been determined in combination.

[C-reactive protein in the maternal serum and risk of fetal infection in premature rupture of the fetal membranes and threatened premature labor]. / C-reaktives Protein (CRP) im mütterlichen Serum und kindliches Infektionsrisiko bei vorzeitigem Blasensprung und drohender Frühgeburt.

In order to find out whether, in the framework of our obstetrical management, determinations of the C-creative protein (CRP) in maternal serum enables recognition of incipient intra-uterine infections, regular controls of the CRP level were performed in 129 patients with premature rupture of membranes and impending premature labour. The maternal CRP levels and the simultaneously determined total leukocyte counts and band counts were compared with the frequency of neonatal infectious diseases up to the 3rd day of life. None of the infants were affected whose mothers never had values above 10.0 mg/l. If he maternal CRP values exceeded the 10.0 mg/l limit, then 6.3%-57.1% of the newborns were affected depending on their birth weight. Therefore, the prepartal CRP diagnosis can, especially in infants with low birth weight, help to determine the risk of infection.

[Rapid determination of C-reactive protein using latex agglutination]. / Die schnelle Bestimmung des C-reaktiven Proteins mittels Latex-Agglutination.

A simple and fast Latex agglutination assay for the determination of C-reactive protein (CRP) is described. The decision range of the assay presented is 7 mg/l; the measuring range extend from 7 mg/l up to 8,000 mg/l. Presented assay allows the cyto-determination of CRP in clinical routine work and therefore is suitable for the early diagnosis of infections in gynecology and obstetrics.

[Serum sialic acid levels in cancer, pregnancy and upper respiratory infections]. / Der Sialinsäuregehalt des Serums bei Krebs, Schwangerschaft sowie Infektionen der oberen Atemwege.

A significant increase in sialic acid content is demonstrable in the sera of cancer patients. Our investigations were performed to find out whether the serum sialic acid level is altered also during pregnancy or with infections of the upper respiratory tract. Our results have revealed a slight increase in sialic acid level to occur only in the last trimester of pregnancy. However, this distinct, though statistically insignificant, increase will not lead to misjudgement in regard to cancer diagnosis, or in case control of this disease. By contrast, in 7 out of 15 patients with infected upper respiratory tract the sialic acid content was clearly above the tolerance limit so that false positive findings may possibly be obtained.