High efficacy of gemcitabine and cisplatin in patients with predominantly anthracycline- and taxane-pretreated metastatic breast cancer.

BACKGROUND: Effective and tolerable regimens are sought specifically in patients who have been pretreated with anthracyclines and taxanes. Gemcitabine and cisplatin demonstrated synergistic activity in vitro and provides a new mechanism of drug interaction. PATIENTS AND METHODS: Previously treated patients with metastatic breast cancer (MBC) were enrolled in a multicentre phase II study. Treatment consisted of gemcitabine (750 mg/m(2)) and cisplatin (30 mg/m(2)) given on day 1 and 8 every 3 weeks. RESULTS: Thirty-eight patients were recruited, all of whom had previously received chemotherapy (35 pretreated with taxanes, 33 pretreated with anthracyclines). A median of 5 cycles of the study treatment was delivered. There were 2 complete and 13 partial responses, for an overall response rate of 40% (95% confidence interval: 23-56%). Thirteen patients (35%) had stable disease. Tumour response appeared independent of previously applied chemotherapy. Median time-to-progression was 6 months and median overall survival was 13.5 months. Main toxicities were leucopenia and thrombocytopenia (grade 3/4 in 26 and 16% of cycles, respectively). Non-haematological toxicity was rarely severe. CONCLUSIONS: Combination chemotherapy with gemcitabine and cisplatin given on 2 out of 3 weeks is well tolerated and active in heavily pretreated patients with MBC, even after prior exposure to anthracyclines and taxanes.

Primary cancer of the fallopian tube. Treatment and results of 37 cases.

OBJECTIVE: A collective of 37 patients with primary cancer of the fallopian tube treated at the Gynecologic Clinic of the Justus Liebig University of Giessen, between 1976 and 1995 was retrospectively evaluated for stage, histo-pathology, treatment and results. PATIENTS: Median age was 61.5 years, FIGO stages: I 17 (45.9%), II 7 (18.9%,. III 12 (32.4%), and IV 1 (2.7%). Histopathology: adenocarcinoma 45.9%, papillary adenocarcinoma 27%, solid carcinoma 8.1%, undifferentiated carcinoma 5.4%, and others 13.6%. TREATMENT: 24 patients (64.9%) underwent complete bilateral salpingo-oophorectomy and hysterectomy (BSOH); 13 (35.1%) had incomplete surgery. POSTOPERATIVE TREATMENT: 31 patients (83.8%) had chemotherapy (since 1982 with platinum), 28 (75.7%) intraperitoneal radionuclides, 23 (62.2%) percutaneous irradiation, and 6 (16.2%) additional vaginal brachytherapy. RESULTS: The cumulative survival rates were 40% for the total of 37 patients, stage I 68%, stage II 29%, stage III 10%, stage IV 0%. From 1976 to 1985 the cumulative survival rate was 25%, from 1986 to 1995, 54%. Stage was a significant prognostic factor (p = 0.0001), surgery, age, chemotherapy and irradiation were not. Severe complications occurred in 7 patients (18.9%): 4 fistulas, 1 myelosuppression, 1 ileus, 1 peritonitis. CONCLUSION: Due to the long period of time and alterations in the mode of treatment the benefit of single treatment modalities could not be evaluated, but prognosis-dependent multimodality treatment (radical surgery, irradiation, platinum-containing chemotherapy) has resulted in higher 5-year survival rates for the last decade.

Complications in connection with venous port systems: prevention and therapy.

Post-operative difficulties apart, venous thrombosis, extravasation and dislocation, obstruction, catheter leakage and local and systemic infections are the typical complications associated with venous port systems. Such complications considerably reduce the benefits otherwise accruing from a reliable access to the venous system of patients with malignant tumours. The vast majority of such disadvantages are attributable to the inexpert handling of ports and, therefore, should be avoidable. This applies to such areas as selecting the right port system, the proper installation of the port chamber and catheter and also to efficient handling and maintenance by trained staff. In may cases it will be possible, with the help of a specific diagnostic investigation, to identify and correct a fault and this ensure that the system installed continues to function. Typical and frequent complications observed (with specific examples) in connection with port systems are described together with preventative measures, diagnosis and therapy.

Pleurodesis with recombinant tumour necrosis factor in gynaecological neoplasms.

Recombinant Tumour Necrosis Factor (rHuTNF) was locally applied to 18 patients with gynaecological tumours and recurrent malignant pleural effusions. Twenty-nine administrations with doses between 0.10 mg and 0.50 mg were carried out. Side-effects were flu-like symptoms (41%), fever/chill (34%), fatigue/malaise (28%), nausea/vomiting (10%), chest pain (14%). A dose-toxicity or dose-response relationship could not be established. Eighty-eight percent of the patients treated with rHuTNF did not suffer from any recurrent effusion within 4 weeks after treatment. Regarding the total survival time after therapy with rHuTNF 78% of all patients did not require any further pleural aspiration. Instillation of rHuTNF appears to be an effective method which can be used for pleurodesis with relatively few side-effects. It is a treatment which can also be applied to patients who are in a poor general state of health. It is especially recommendable since it can be successfully applied even after other pleurodesis devices have failed.

Venous port systems in the field of gynaecological oncology.

In the field of gynaecological oncology, which is characterised by the frequent application of cytotoxic drugs strongly necrotising to tissue, fully implantable venous port systems are of particular relevance. Frequent and serious complications such as infection, thrombosis, obstruction, leakage, or paravasation detract considerably, however, from the advantages otherwise deriving from a safe and reliable means of accessing a patient's venous system. Most complications are caused by the inexpert handling of these fully implantable catheters and should, therefore, be avoidable. In many cases, it will be possible after efficient diagnosis to solve the complication and keep the port functioning. On the basis of 8 actual cases typical and frequent complications observed in connection with port systems are described, together with preventive measures, diagnosis and therapy.

Recombinant tumour necrosis factor in the local therapy of malignant pleural effusion.

rHuTNF was locally applied to 26 patients with diverse advanced tumours and malignant pleural effusions following maximum possible drainage of their pleural cavities. 46 instillations (an average of 1.8 per patient) with doses between 0.10 mg and 0.50 mg were carried out. The total doses ranged from 0.15 mg to 1.01 mg per patient. 41% of the instillations resulted in flu-like symptoms, 35% fever/chill, 24% fatigue/malaise, 11% nausea/vomiting and 11% chest pain. All toxicities were fully reversible and could be treated successfully. There was no apparent relation between dose and side-effects. Of those patients treated primarily with TNF, 87% did not suffer from any recurrent effusion within 4 weeks after treatment. In patients who had already been treated employing other methods, this figure was 86%. Complete drainage of the pleural cavity was not absolutely necessary before application of TNF. Intrapleural instillation of TNF appears to be an effective method for achieving pleurodesis with relatively few side-effects and can be successful even after other methods have failed. It is a method which can also be applied to patients who have a poor general state of health.

[Menopausal symptoms in breast carcinoma patients. Is effective treatment possible?]. / Wechseljahresbeschwerden bei Mammakarzinompatientinnen. 1st eine effektive Be

Vasomotor complaints occuring during the menopause need treatment, and this also applies to patients with cancer, whose quality of life, already reduced by the disease, its treatment and sequelae of therapy, would otherwise decline further. While estrogen replacement therapy is employed to treat climacteric symptoms, the fact that estrogens may stimulate the growth of the mammary carcinoma cells would appear to rule out estrogen replacement in patients with breast cancer. Against this background, a stepped treatment plan is recommended, in which the initial application of symptomatic measures/placebos is followed by non-hormonal drugs and, finally, hormones. Should the results obtained be inadequate, and distress-causing symptoms persist, estrogen replacement treatment aimed at improving quality of life may be employed as a last resort, after a careful weighing up of the risks and establishment of an "informed consensus".

[Congenital ectopic ureteral orifice as the cause of 70 years incontinence]. / Konnatale ektope Uretermündung als Ursache siebzigjähriger Inkontinenz.

A female patient of 70 years of age had been suffering from absolute incontinence of urine from birth. Although doctors had been consulted repeatedly, the real cause had never been discovered. It was now possible to identify the cause of the complaint by means of transvaginal contrast visualisation: ureter orifice and vagina were ectopically conjoined.

[Morphologic comparison of stroma rich and stroma poor tumors in the agar colony-forming test]. / Morphologischer Vergleich stromareicher und stromaarmer Tumoren im Agarkoloniebildungstest.

In the study reported here the morphologic relationship between the original tumor and a colony cultured in vitro was investigated in stroma-rich and stroma-poor tumors. The colonies, cultured in a double-layer agar system were marked with graphite and bedded in paraffin after centrifuging. Subsequent preparation of the microtome sections was in accordance with customary histologic methods. Taking an ovarian carcinoma as an example, far-reaching agreement between the original histologic findings and the section through the colony in the light-microscopic image was demonstrated. In contrast, the tumor cell colonies in mammary carcinomas, which are typically representative of stroma-rich tumors, generally showed less similarity to the histologic structure of the mother tumor, since the formation of connective tissue cannot be induced due to the lack of mesenchymal elements in the agar culture. However, under comparable in vivo and in vitro conditions, e.g., tumor manifestation in performed cavities, there was, also with mammary carcinomas, a similar morphologic analogy between the original tumor and the clone, as in cell-rich neoplasms. The possibility of identifying malignancy directly in colonies and knowledge of their morphologic relationship to the primary tumor increase the relevance of chemosensitivity testing in colonization tests.

[Hysterography with afterloading-applicator in place. A simple method for improving the treatment planning of uterine cancer]. / Die Hysterographie bei liegendem Afterloading-Applikator. Eine einfache Methode zur Verbesserung der Bestrahlungsplanung des Korpuskarzinoms.

Anatomical configurations often are an obstacle to a convenient dose-distribution in intracavitary afterloading irradiation. Multiple applicators (splay applicators, twin applicators) cannot be introduced in all cases because of the necessary cervix dilatation. In several cases can be demonstrated, that a defined intracavitary irradiation is possible only by hysterographic control of the intrauterine position of the applicator. By this control generally a mono-applicator is sufficient, which can be placed according the anatomy of the uterine cavity in each session. For this purpose a simple hysterographic method with applicator in position is demonstrated, which requires only few additional effort during intracavitary irradiation.

[Recent trends in the therapy of vaginal carcinoma]. / Neuere Gesichtspunkte in der Therapie des Vaginalkarzinoms.

The presented paper gives a historic review of the change from the contact therapy to the percutaneous irradiation. The dominating role of radiotherapy compared to surgery is pointed out. With the help of therapeutic planning in Giessen an aimed pendulum irradiation, a high-volume percutaneous irradiation, a modern high-intensity afterloading system (Buchler), and an interstitial therapy are reported. Recently published important cure rates are shown in a table. The 5-year survival rate of 78 patients in Giessen from 1957-1975 was 42.3%. The discussion concentrates on the tolerance dose of the vagina according to the different dose rates and fractionations.

[The behavior of tumor cells of female genital carcinomas in vitro under irradiation with different activities of radiogold (author's transl)]. / Das Verhalten von Tumorzellen weiblicher Genitalkarzinome in vitro unter Bestrahlung mit unterschiedlichen Aktivitäten von Radiogold.

A method is reported which permits an assessment of the effect of radiation, especially with 198Au, upon primary cultures. Thus, a statement of the individual radiation sensitivity of a tumor can be made, which is not possible with conventional methods. The tumors investigated by us exhibited a dependence of their cells in vitro upon the activity of the radiogold, and different tumors revealed a different radiosensitivity to the same dose.

[Effect of colloidal 198Au on cell cultures of human tumors (author's transl)]. / Die Wirkung von kolloidalem 198Au auf Zellkulturen menschlicher Tumoren. Eine morphologische Studie.

The authors observed the effect of colloidal 198Au on the morphology of cells in 19 cell cultures of human tumors. Partly, there were typical modifications. The reactions of the individual cells were different and the radiosensibility and dependence on the dose seemed to vary with different concentrations of the radiogold. The importance of this study with regard to clinical problems is discussed.

[Changes in the electrolyte and acid-base equilibrium during the first days of life]. / Veränderungen im Elektrolyt- und Säure-Basen-Haushalt während der ersten Lebenstage

The concentrations of potassium, sodium and magnesium in plasma, red corpuscels and acid-base status were measured during the first five days of life. Significant differences were observed during this period of life, these values also differ markedly from those of adults. The causes of the particular conditions of the neonates are complex and not all known at present.

[Infantile and hypoplastic uterus: a contribution to overcome the confusion of terms (author's transl)]. / Infantiler und hypoplastischer Uterus. Ein Beitrag zur überwindung einer Begriffsverwirrung

The confusion of terms between the radiological literature and the gynaecological and anatomical literature regarding the definitions of the infantile and the hypoplastic uterus are described. The history of this confusion is traced. The two types of uterus were clearly defined by K. Menge and K.v. Oettingen in 1930. The infantile uterus shows an abnormal relationship between the length of the cervix and the length of the uterine cavity of 1:1 or 2:1, whereas the hypoplastic uterus shows a normal relationship between the length of the cervix and the length of the uterine cavity of approximately 1:2.