Abstract: Vinorelbine (Navelbine) is a new, semisynthetic 5'Nor-vinca-alkaloid, modified on the catharantine ring, developed by Pierre Fabre Medicament. Vinorelbine is a potent as the other vinca alkaloids to inhibit mitotic microtubule polymerization. On the other hand, its activity is lower on axonal microtubule. Preclinical studies have shown its broad spectrum of activity in vitro and its antitumoral efficacy comparable or higher to that of other vinca alkaloids against murine tumors and in xenograft models. The main experimental toxicity of vinorelbine is a reversible leucopenia. No neurotoxicity was evidenced in rats, dogs and monkeys. After i.v. injection in patients, the plasma kinetic is described by a tricompartimental model with a high clearance, a very large volume of distribution and a long terminal half life, intermediate between vincristine and vinblastine. Tissue uptake of vinorelbine is very intense, probably related to its high liposolubility, leading to high tissue concentration compared to plasma. Phase I trial using weekly i.v. administration demonstrated a maximal tolerated dose (MTD) of 27.5 to 35.4 mg/m2 and the recommended dose was established at 30 mg/m2 weekly. In Phase II studies, Vinorelbine was shown to be effective in at least 4 types of cancer: Non-small cell lung cancer (remission rate: 33%), breast cancer (45%), advanced ovarian cancer (15% in heavily pretreated patients), Hodgkin's disease (90%). In all the trials, side effects are generally limited to a reversible and non-cumulative leucopenia. Neurotoxicity appears to be mild, similar to that observed with vinblastine and much less severe than with vincristine. No evidence of cardiac, pulmonary, renal, hepatic or other organ system toxicity has emerged.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: 20 patients with neuropathic pain syndromes due to tumor-infiltration, who had not responded to conventional analgesics including strong opioids, received additional combination anti-convulsant and an

Abstract: Continuous administration of gonadotrophin-releasing hormone (GnRH-)analogues leads to a receptor-down regulation of pituitary GnRH-receptors and subsequently inhibits ovarian hormone production Since October, 1984, 118 evaluable pre- and perimenopausal patients (median age 42, range 25-55 years) with metastatic breast cancer were entered into an open phase II multicenter trial to evaluate efficacy of this new treatment modality Patients were treated with the GnRH-analogue Goserelin (36 mg depot sc every 4 weeks) as first line therapy and followed up until progression Mean serum gonadotrophins LH and FSH were significantly suppressed by Goserelin Within 2-3 weeks, mean serum E2 values decreased to values seen in castrated women (less than 30 pg/ml) Overall objective response with complete and partial remissions (CR + PR) was achieved in 449% of patients with a median time to progression (mTTP) of 59 weeks, (range 20-163 weeks), no change (NC) in 280% with a mTPP of 27 weeks (range 16-101 weeks), and progression (P) in 271% Responses were seen in ER-positive as well as ER-negative tumors, and in patients with different sites of metastases (locoregional, bone, visceral, multiple) The value of different prognostic factors in relation to response rates, time to progression and time to death (overall survival) is discussed Median overall survival (time from beginning of palliative Goserelin treatment to death) was 148 weeks(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: Treatment failures following putatively curative resections for circumscribed neoplasms are well recognized and the recurrence patterns have been analyzed. These observations compel us to reshape our conceptual model, for such cancers, from one of malignancy as a localized process to that of a regionalized process. Consequently, treatments should evolve to include not only the primary cancer (removedby surgery) but also the entire anatomic region (peritoneal cavity). Regionalized processes command a combined-modality approach to effect cure or, at least, to favorably alter the natural history of the disease. It follows, then, that if for a given neoplasm the available agents are not ideal and, furthermore, that no new agents have been developed in the recent past that offer a hope of improved survival ; we must exploit the agents at hand in the most effective manner.

Abstract: A clinical phase I trial with an oral formulation of miltefosine (MIL) was performed in patients with various advanced malignant diseases. The capsulated drug (50 mg or 100 mg capsules) was given once a week over a period of twelve hours with a starting dose of 100 mg (2x50 mg). Dose escalation proceeded up to 300 mg per week. At least three patients were treated at each dose level for eight weeks or until progressive disease or dose limiting toxicity occurred. 34 patients entered this study with 26 patients completing one eight-week course of therapy. Only gastrointestinal side effects were seen, namely nausea and vomiting or diarrhea up to grade III (WHO). Severity of these side effects was dose-related, but there was considerable individual variation. MTD was reached at the 300 mg dose level. Pharmacokinetic studies performed at this dose level showed peak plasma levels of approx. 15 nmol/ml and a plasma half life in excess of eight days after application on one single day. No objective remission has been seen in the patients of this study.

Abstract: Combination chemotherapy with etoposide, leucovorin and 5-FU (ELF) was investigated in a phase-II study in patients with advanced gastric carcinoma (stage III and IV). Only ambulatory patients (performance status WHO ≤2) above 65 years or younger patients with cardiac disease were entered. A remission rate of 53% could be achieved in 51 evaluable patients, including 12% complete remissions. One toxic death was observed. Remission rate was particularly high in patients with locally advanced disease (70%, 7/10 patients). Median remission duration was 8 months, median overall survival 11.5 months. Patients with peritoneal carcinosis lived significantly shorter than those with other distant metastases (P

Abstract: Idarubicin is a new anthracycline derivative with therapeutic efficacy in metastatic breast cancer. In a phase II trial we treated 23 patients with advanced breast carcinoma and favourable prognostic factors. Oral dose of idarubicin was 15 mg/m2 day 1-3 repeated every 3 weeks. All patients were pretreated with hormones. Idarubicin was administered as first line chemotherapy. 20 patients were evaluable for response: 3 patients achieved partial remission, 12 patients stable disease; tumour progression occurred in 5 patients. 3 patients were not evaluable for response because only 1 treatment cycle was administered. Main toxicites were leukopenia (median WHO-grade: 2,r:0-4), nausea and vomiting (median: 1,r:0-4) and alopezia (median: 1,r:0-3). 1 patient died in septic shock: Immediately after the administration of one idarubicine cycle, she was extensively irradiated because of bone metastasis. The fatal course of the disease in this patient does not depend only on the idarubicin therapy, but also on the extensive bone infiltration and on intensive radiation therapy. Idarubicin proved to be an effective drug in metastatic breast cancer with low systemic toxicity and the advantage of oral administration. The drug is an enrichment of therapeutic armament, especially in patients with soft tissue and bone metastasis.

Abstract: Fifteen patients (8 female, 7 male) with advanced melanoma received intravenous injections of a pyrogenic bacterial lysate consisting of streptococci and serratia marcescens. In three cases with skin

Abstract: Two types of local chemotherapies were combined intraoperatively with gastric resection for gastric cancer. One chemotherapy was intralymph nodal injection of mitomycin C adsorbed on small activated c

Abstract: Results of surgical treatment for squamous cell carcinoma of the esophagus are not satisfactory. The relatively low resectability rate, extensive surgery associated with a relatively high morbidity and mortality as well as the high risk for local recurrence and distant metastases influence the unfavorable prognosis. The improvement of these risk factors has been attempted through multimodality therapy such as preoperative radiotherapy and/or chemotherapy. Even with the advantages of such a treatment plan which was documented in different phase II studies, it has not been possible to prove in randomized studies its advantage in comparison to immediate surgery. But there is some evidence that multimodality therapy may benefit some patient groups. The definition of these groups has to be the task of future studies. Important selection criteria may be tumor size, tumor localization and response to preoperative chemo- and/or radiotherapy. Before these questions are answered in further studies, the best treatment for non metastatic localized, esophageal carcinoma is still radical surgical resection.

Abstract: Consideration of significant prognostic factors has been omitted in most studies on adjuvant treatment of colorectal carcinoma published to date. Patients with regional lymph node metastases were not classified according to the currently valid UICC/AJCC pN classification. Neither surgical methods (type of surgery, surgical procedure, technique of tumor mobilization, intraoperative tumor cell dissemination), nor a series of further independent factors, which, in addition to TNM and surgical treatment influence prognosis, have been taken into account. For future studies, data collection according to the recently published recommendations of the ‘International Documentation System for Colorectal Cancer (IDS for CRC)’ as well as the compilation of quality control data related to patient selection should be made mandatory.

Abstract: 525 patients with acute lymphoblastic leukemia (ALL) between the ages of 15 and 44 were treated according to the German study protocol 41 patients received HLA-identical sibling bone marrow transplants in first remission Disease-free survival was compared in patients with transplants and patients who were intended for further chemotherapy After adjusting for potential biases, prognostic profiles of the two groups could be determined, the impact of time-to-transplant bias estimated and similar patients compared after appropriate adjustments The initial patient characteristics of both groups were quite comparable as was the treatment outcome The three year probability of disease-free survival was 34 % (95 % confidence interval: 16% to 52%) in both groups after statistical adjustment

Abstract: 17 patients with advanced low-risk breast carcinoma not previously pretreated by cytostatic agents were treated by Vinorelbine (VIN), 5’-Nor-anhydro-vinblastine, a new semisynthetic compound of the vi

Abstract: Since its pioneer days, liver transplantation for malignant liver tumors has decreased worldwide, the present percentage within Europe being roughly 15%. There are mainly two reasons for this decrease

Abstract: With the introduction of an ambulatory community-centered comprehensive cancer care system in Hamburg, based on private practice outpatient day clinics in 1976, it became obligatory to study the psychosocial consequences both for the patient and the relatives taking care of them and their impact on private and professional cancer nursing. In a common effort of qualified cancer nurses, medical psychologists and oncologists, we visited 59 surviving dependents who had cared for their relatives who had died from cancer four to twelve weeks before. In semi-structured interviews comprising 117 questions we studied the subjective and objective burden related to psychological, social, physical and nursing areas. In 85% the nursing service was predominantly supported by the spouses, in 15% by children or parents. The average duration of total dependence of the bed-ridden patient was 16 days. In 94%, gratitude for and acknowledgement of the deceased were the dominant motivation, in 44% the relations towards the patient grew more affectionate. Being responsible for the terminal care was experienced as too heavy a burden because of insufficient medical (39%) or nursing support (35%), 64% claimed an inadequate preparation for death as a sudden and frightening event. In retrospective, 76% of the caring relatives would again prefer terminal home care to hospital services. Following a discussion of problematic methodological aspects of the responses to our interviews, consequences are presented for an improved support of the terminally ill patient and his caring family, as well as for professional education and further development of the hospice system in Germany.

Abstract: There is growing consensus that patient-based criteria for assessment of the quality of life should supplement the judgements of physicians. There is, however, no widely accepted instrument that fulfills all stipulations. We therefore propose a questionnaire that can be supplemented according to specific problems in various clinical trials as well as under clinical routine conditions. Its modules have been tested for reliability, responsiveness to change, content, concurrent validity, predictive validity, feasibility, and compliance in a prospective study using 488 single assessments with a total of 31,073 evaluable answers and a total of 2,961 curves. The questionnaire is proposed as a compromise between desired information and the patients’ compliance.

Abstract: Der Einsatz von Steroidhormonen als Tragermolekule zur Anreicherung von Radionukliden in Tumorzellen erscheint als eine interessante neue Therapiestrategie vor dem Hintergrund, das zahlreiche Karzinom

Abstract: Zur Festlegung des Stellenwertes der Staging-Laparotomie (LAP) bei Morbus Hodgkin analysierten wir die klinischen und pathologischen Befunde von 282 neu diagnostizierten Patienten der klinischen Stadi

Abstract: In a prospective randomized study with a population of 40 patients suffering from metastatic colorectal cancer, the efficacy of additional Rubratin (N-CWS), an unspecific therapeutic agent, was tested in combination with cytostatic treatment. After allocating patients to either intra-arterial (liver metastases only) or intravenous (extra-hepatic metastases) 5-FU chemotherapy, patients were randomized for combined chemo-/immunotherapy (5-FU/Rubratin (N-CWS)) or chemotherapy (5-FU) alone. The toxic side effects were not different from those generally seen in 5-FU chemotherapy. Administration did not significantly add to the side effects. On the other hand, we saw local erythema and indurations in most patients following intra-cutaneous injections of Rubratin (N-CWS). More than one third of these patients refused to continue this kind of immunotherapy. There were no significant differences in both chemotherapy groups, neither concerning median survival nor median progression-free intervals. The additional immunotherapy did not influence these results.

Abstract: In einer multizentrischen Studie wird gepruft, ob der Einsatz von Hydroxyurea oder von Interferon alpha anstatt von Bulsulfan die Dauer der chronischen Phase bei Patienten mit Philadelphia-Chromo-som-positiver CML verlangert. Zusatzliche Ziele sind die Prufung, ob sich der Typ der Krankheitsevolution und die terminalen Phasen bei den verschiedenen Therapiegruppen unterscheiden, sowie die pro-, spektive Erkennung von Prognosekriterien fur die Dauer der chronischen Phase. Bis zum 5.9.1990 waren 593 CML-Patienten randomisiert, 221 fur Busulfan, 228 fur Hydroxyurea und 144 fur Interferon alpha. Das Durchschnittsalter aller Patienten liegt bei etwa 51 Jahren. Bis zum Stichtag am 30.4.1990 hatten 106 Patienten das Ende der chronischen Phase erreicht, 126 waren verstorben. Die mediane Uberlebenszeit der Philadelphia-positiven Patienten betrug 3,95 Jahre, die aller Patienten 3,75 Jahre. Die mittlere Beobachtungszeit betrug 1,34 (1,60) Jahre. Erwartungsgemas besteht bisher noch kein signifikanter Unterschied zwischen den drei Studienarmen, wenn auch im Hydroxyurea-Arm weniger Nebenwirkungen beobachtet wurden.

Abstract: The implantation of a small silicon catheter for repeated intravenous applications of drugs in laboratory animals (rats) is described. Under an operation-microscope, the catheter is inserted into the external jugular vein and remains in situ in a skin pocket during the treatment. By dissecting the wound, multiple fractions of drugs can be administered via the catheter at intervals of days or weeks. The method has the advantage that in long-term studies with rats, intravenous injections or infusions of cytostatic drugs are possible with high accuracy.

Abstract: A 16-year old girl died from a bilateral teratoma of the ovary after she had been treated for a bilateral retinoblastoma at the age of 9 months. Remarkable are the similar morphological patterns of th

Abstract: To evaluate the effect of immunochemotherapy starting in the early postoperative period for stage III gastric cancer, 330 patients after radical subtotal gastrectomy were randomly allocated to receive immunochemotherapy (n = 159), chemotherapy (n = 77) and surgery alone (n = 94). For immunotherapy, a Streptococcus pyogenes preparation (Picibanil) was administered intramuscularly with a dosage of 1.0 KE every week from the fourth or fifth postoperative day on. Mitomycin C 4 mg/50 kg and 5-Fluorouracil 500 mg/50 kg were given intravenously twice a week for the first two weeks, and then weekly for the next six weeks. Thereafter, oral 5-Fluorouracil (600 mg/50 kg) was given daily. Immunochemotherapy was continued for 24 months if possible. In all treatment groups, the immune status using skin tests, lymphocyte count and stimulation as well as cytotoxicity was investigated before an operation and at the third and fourth postoperative months. Five-year survival rates of groups 1, 2 and 3 were 45.3%, 29.8% and 24.4% respectively, the difference between the immunochemotherapy group and the other two groups being significant. All postoperative immune parameters showed more favorable values in the immunochemotherapy group. The data suggest that the postoperative adjuvant unspecific immunotherapy is able to prolong survival for stage III gastric cancer patients.

Abstract: Um Inanspruchnahme und Erfolg von stationaren Nachsorgekuren fur onkologische Patienten im Zusammenhang mit dem Bewaltigungsver-halten zu untersuchen, wurde eine unausgelesene Stichprobe von 100 Tumor

Abstract: With a few notable exceptions, surgical adjuvant therapy has little altered the survival of patients with gastrointestinal cancers. Progress has resulted from earlier diagosis due to fiberoptic endosc

Abstract: Multidrug-resistance (mdr) of tumor cell-lines to several natural product cytotoxines (e.g. vinca alkaloids, podophyllotoxine derivatives and anthracycline derivatives) is often related to enhanced ex

Abstract: The determination of clinical stage in hairy cell leukemia is hampered by the lack of common criteria. Furthermore, clinical stages in which the disease should be treated have not yet been defined. In