[Detection of disseminated carcinoma cells in bone marrow and peripheral blood in primary breast cancer with RT/PCR of parathyroid hormone-related protein (PTHrP)].

The analysis of tissue specific gene expression by reverse transcription based RT/PCR methods is currently evaluated as a method for the detection of tumor cell dissemination in patients with cancer. Breast cancer tissues express PTHrP and the level of PTHrP expression in the primary tumor correlates with the incidence of metastases in the bone. We applied a RT/PCR assay of PTHrP to detect tumor cells in the mononuclear cell fraction of peripheral blood (pb) and bone marrow (bm) of patients with newly diagnosed breast cancer.

Systemic therapy for treating locoregional recurrence in women with breast cancer.

Background: Between 10% and 35% of women with operable breast cancer will experience an isolated locoregional recurrence following their primary treatment. There is currently no good evidence that adjuvant systemic treatment is effective in this situation and there is no standard treatment for women who have such a recurrence.

Objectives: To investigate whether additional systemic treatment will improve the result of local therapy in regard to relapse-free and overall survival in women with potentially curatively resected loco-regional recurrence following breast cancer, who have not had a previous or synchronous distant metastases.

[Introduction of studies by the German Breast Center Study Group (GBSG)].

The GBSG is actually running two studies on breast cancer therapy: GBSG-5 addresses the necessity of radiotherapy following tumor removal, in breast preserving treatment of pT1N0M0 G1 breast cancer. The other question to be answered in a randomised 2- by 2-design is related to the replacement of radiotherapy by a 5-year treatment with tamoxifen. Up till now, 341 patients have been randomised.

Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancer: a randomised trial. European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group, the Gruppo Interdisciplinare Valutazione Interventi in Oncologia, and the Japanese Foundation for Cancer Research.

Background: There is conflicting evidence on the efficacy of regional adjuvant chemotherapy, via portal-vein infusion (PVI), after resection of colorectal cancer. We undertook a randomised controlled multicentre trial to investigate the efficacy of PVI (500 mg/m2 fluorouracil plus 5000 IU heparin daily for 7 days).

Methods: 1235 of about 1500 potentially eligible patients were randomly assigned surgery plus PVI or surgery alone (control).

Grading system for breast cancer.

As recurrence rates in breast cancer depend significantly on degree of malignancy (6-9) and mitotic rates as part of the grading system are difficult to assess in exact manner, we widened the grading system by evaluation of the proliferative compartment to get more information about proliferation activity as an important factor for tumor-progression (15, 16). This additional analysis can be used as a control factor for the correctness of the evaluation of mitotic activity. We practice this procedure at present as a "working formulation".

Eight-year results of a prospective non-randomised study on therapy of small breast cancer. The German Breast Cancer Study Group (GBSG).

In this report, the results of the first controlled clinical trial on breast cancer in Germany, begun in 1983, are presented after a median follow-up of 8 years. Four-year results have been previously published. In pT1 N0 M0 breast cancer, mastectomy as the standard treatment was to be compared with tumorectomy plus radiotherapy to the remaining breast tissue.

Final results of a phase III clinical trial on adjuvant intraportal infusion with heparin and 5-fluorouracil (5-FU) in resectable colon cancer (EORTC GITCCG 1983-1987). European Organization for Research and Treatment of Cancer. Gastrointestinal Tract Cancer Cooperative Group.

In this phase III clinical trial conducted by the Gastrointestinal Tract Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer (GITCCG-EORTC), we evaluated the effect of adjuvant intraportal infusion of heparin (HEP) and 5-fluorouracil (5-FU) on overall survival, disease-free survival and time to progression in patients with resectable colon cancer. From January 1983 to June 1987, 235 patients were randomised from 14 institutions in seven European countries: 79 patients made up the control group (control): 72 the portal vein infusion group given heparin alone (5000 IU daily x 7 consecutive days) (HEP); 84 the portal vein infusion group given heparin (5000 IU daily x 7 consecutive days) and 5-FU (500 mg/m2 daily x 7 consecutive days) (HEP/5-FU); 34 patients were considered ineligible. The 199 patients considered eligible were well balanced for age, sex, Karnofsky index, tumour location, surgery, surgical procedure and Dukes' stage.

Phase II evaluation of 5-fluourouracil plus folinic acid and alpha 2b-interferon in metastatic colorectal cancer.

Biochemical modulation of 5-fluorouracil (5-FU) by folinic acid (FA) increases the response rate in patients with metastatic colorectal cancer compared to 5-FU alone. Phase II trials also demonstrated increased efficacy when interferon was added to 5-FU. In two consecutive trials, 76 patients were treated on days 1-5 with FA 200 mg/m2 plus interferon 5 x 10(6) U/m2 and 5-FU 350 mg/m2 as intravenous bolus injection (n = 33, regimen A) or 5-FU 500 mg/m2 as 2-hour infusion (n = 43, regimen B), repeated every 3 weeks with individual 5-FU dose escalation in steps of 50 (regimen A) or 100 mg/m2 (regimen B).

[Therapy of the small breast carcinoma--generalized conversion to breast-saving treatment in Germany. 8 years results].

In the prospective nonrandomized observation study "Therapy of Small Breast Cancer", which was the first multicenter trial on breast cancer ever conducted in Germany, mastectomy (303 cases) was compared with breast-preservation therapy (733 cases) in patients with stage pT1N0M0 breast cancer. After a median follow-up of 8 years, there is no difference between the treatment modalities with regard to disease-free and overall survival which compares well with the results of international randomized studies. There is no difference in treatment outcome between centers specialized in the therapy of breast diseases in comparison to less experienced institutions as long as a high standard of treatment performance is guaranteed by reference centers.

[Brief interdisciplinary oncology: a model for ambulatory, multimodal treatment of tumor patients].

Since 10/1994 the Interdisziplinäre Kurzzeit-Onkologie (IKO) is an outpatient department for the treatment of patients with cancer used by the departments of hematology/oncology and surgery. Between 09/1995 and 02/1997, 818 patients received 2024 cytotoxic therapies with neoadjuvant (15%), adjuvant (65%) or palliative (20%) intention-mostly within multicenter clinical studies. Ambulatory operations like removal of lymph nodes for diagnosis or the implantation of venous catheter systems prepared the way for specialized modalities of cancer therapy.

Reverse transcriptase/polymerase chain reaction analysis of parathyroid hormone-related protein for the detection of tumor cell dissemination in the peripheral blood and bone marrow of patients with breast cancer.

Tumor cell dissemination in the bone marrow is an independent prognostic marker for relapse and survival for patients with primary breast cancer. Parathyroid-hormone-related protein (PTHrP) is expressed in most primary tumors and bone metastases of patients with breast cancer. PTHrP acts as an autocrine growth factor for breast cancer cells in vitro and there is evidence that it is especially important for osseous metastasis.

Leakage measurement during selective limb perfusion using a gamma probe.

The objective of this study was to establish a probe system for intraoperative quantitative leakage measurement during selective limb perfusion for adjuvant high-dose chemotherapy in patients with malignant melanomas. We used a portable gamma probe with digital display and investigated the physical properties in a phantom study simulating blood pool activity at different angles of the probe to the surface and different distances. In 20 patients the limb circulation was surgically separated from the systemic blood circulation, and the limb was then selectively perfused (cytostatics added) for 60 min.

Interferon-alpha does not improve the antineoplastic efficacy of high-dose infusional 5-fluorouracil plus folinic acid in advanced colorectal cancer. First results of a randomized multicenter study by the Association of Medical Oncology of the German Cancer Society (AIO).

Background: High-dose 5-FU given weekly as a 24-h infusion in combination with folinic acid (FA) has been associated with low toxicity and a high response rate. Interferon-alpha (IFN) either alone or in combination with FA has also improved treatment results by modulating 5-FU activity. We therefore initiated a randomized multicenter trial comparing the ability of FA or IFN to modulate infusional 5-FU.

Randomized 2 x 2 trial evaluating hormonal treatment and the duration of chemotherapy in node-positive breast cancer patients. German Breast Cancer Study Group.

Purpose: In 1984, the German Breast Cancer Study Group (GBSG) started a multicenter randomized clinical trial to compare the effectiveness of three versus six cycles of 500 mg/m2 cyclophosphamide, 40 mg/m2 methotrexate, and 600 mg/m2 fluorouracil (CMF) on day 1 and 8 starting perioperatively with or without tamoxifen (TAM) (3 x 10 mg/d for 2 years). The aim of the trial was to compare recurrence-free and overall survival between the different treatment modalities.

Patients And Methods: During 5 years, 41 institutions randomized 473 patients (3 x CMF: 145; 3 x CMF + TAM: 93; 6 x CMF 144; 6 x CMF + TAM: 91).

Randomised trial of epirubicin versus fluorouracil in advanced gastric cancer. An International Collaborative Cancer Group (ICCG) study.

Background: It is not yet established whether doses of epirubicin equitoxic to adriamycin are more effective in the treatment of locally advanced or metastatic gastric cancer.

Patients And Methods: Seventy patients with advanced gastric cancer were randomised to receive fluorouracil (500 mg/m2 days 1-5 every three weeks) or epirubicin (100 mg/m2 every three weeks), with doses escalating to a maximum dose of 700 mg/m2 of fluorouracil or 140 mg/m2 of epirubicin.

Results: No patients attained complete response.

Quality control review for radiotherapy of small breast cancer: analysis of 708 patients in the GBSG I trial. German Breast Study Group (GBSG).

Within six years between November 1983 and December 1989 the German Breast Cancer Study Group (GBSG) conducted a prospective multicenter trial on the treatment of pT1 pN0 M0 breast carcinoma. Out of 1036 eligible patients from 69 hospitals, a total of 733 underwent breast preservation surgery and postoperative radiotherapy. A detailed quality control (QC) screening of 708 available radiotherapy records was performed by the radiotherapy reference center.

The prognostic effect of histological tumor grade in node-negative breast cancer patients.

The prognostic effect of histological tumor grade was evaluated in 1036 patients with early breast cancer (pT1 pN0 M0) entered into a trial comparing mastectomy and breast preserving treatment. All analyses were adjusted for the factors treatment, patients' age, and tumor size. Tumor grade was defined according to Bloom and Richardson based on the sum of scores assigned to each of three histological features: 1) degree of differentiation, 2) pleomorphism, and 3) mitotic index.

[Initial results of the Project of the German Breast Cancer Study Group on "Breast saving therapy of the small breast cancer"].

In the German Breast Cancer Study Group (GBSG) multicenter trial "Breast preservation in small breast cancer" 1119 patients were accrued over a period of six years. The study was originally designed as a randomized trial which had to be changed into a prospective observation study. A high therapeutic standard was guaranteed by quality control.

Breast preservation versus mastectomy in early breast cancer--1991 update of the GBSG 1--protocol and prognostic factors. The German Breast Cancer Study Group.

In 1983, the German Breast Cancer Study Group (GBSG), sponsored by the Federal Ministry of Research and Technology, started a prospective multicenter trial on the treatment of early breast cancer (pT1 pN0 M0). This was preceded by a three-year reviewing period because of some novelties of medical, juristical and ethical problems in the FRG. University and, in the majority, community hospitals participated, combining all together 69 different institutions.

Therapy of small breast cancer: a prospective study on 1036 patients with special emphasis on prognostic factors.

In 1983, The German Breast Cancer Study Group, sponsored by the Federal Ministry of Research and Technology, started a prospective multicenter trial on the treatment of early breast cancer pT1 pN0 M0. Treatment consisted of initial tumorectomy with microscopically free margins and lower axillary dissection. After conformation of a pT1 pN0-stage, additional treatment was either mastectomy or adjuvant radiotherapy (50 Gy in 25 fractions to the entire breast plus 12 Gy electron boost).

Kinetics of melphalan leakage during hyperthermic isolation perfusion in melanoma of the limb.

The kinetics of melphalan leakage into the peripheral blood were studied in 21 patients undergoing hyperthermic isolation perfusion of the upper or lower limb as an adjuvant treatment in high-risk melanoma; in 5 patients cisplatin was added. The melphalan concentrations in the peripheral blood rose predominantly during the first 20 min of perfusion and levelled out to an apparent steady state of about 0.28 micrograms/ml in upper extremity perfusions, and 0.

[Decreased plasma zinc levels in metastatic breast cancer].

Zinc is an essential component of many metalloenzymes for DNA and proteinsynthesis including RNA and DNA polymerases. It has been shown by several investigators that zinc is accumulated in breast cancer tissues. To investigate a possible relation between plasma zinc levels and tumor load, plasma zinc levels were evaluated in 76 patients with non metastatic breast cancer (no evidence for disease after mastectomy) and in 66 patients with metastatic breast cancer.