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Biomedical subjects

K Brunner

Publications and source records attributed to K Brunner.

At least 19 recordsLinked to original sources
PubMed1992

Feasibility of quality of life assessment in a randomized phase III trial of small cell lung cancer--a lesson from the real world--the Swiss Group for Clinical Cancer Research SAKK.

Between 1985 and 1990 the Swiss Group for Clinical Cancer Research (SAKK) for the first time assessed quality of life (QL) variables in 188 patients in a multicenter small-cell lung cancer trial that compared two different regimens of combination chemotherapy. QL-assessment was scheduled at the beginning of each of the six treatment cycles. The self-rating QL questionnaire included an early version of the EORTC QL questionnaire, a mood adjective checklist (Bf-S) and a single linear analogue scale (LASA) measuring general well-being. Compliance with completion of the scheduled questionnaires varied between 37% and 58% over the six cycles, and between 21% and 68% among the 7 participating institutions. Mean compliance was 49%. The institution was found the only significant factor predicting compliance (p < 0.001). Patient age, sex, education and biological prognostic factors at randomization were not predictors of compliance. Although compliance was poor, the data received was of high quality. We suggest practical guidelines for improving compliance with QL data collection in multicenter clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Considerable side effects of chemoembolization for colorectal carcinoma metastatic to the liver.

The feasibility of one whole liver chemoembolization (CE) procedure with Angiostat, a vasoocclusive collagen, mitomycin, doxorubicin, and cisplatin was evaluated in eight patients with unresectable colorectal carcinoma metastatic to the liver and good performance status. One heavily pretreated patient showed a partial response in the liver lasting 188 days. Five patients had stabilization of the disease for 85-150 days. The side effects of the treatment were considerable with a fatigue syndrome lasting up to eight weeks, chemical and ischemic hepatitis, severe thrombopenia (WHO grade 4 in 2 pts) and icterus being the most disturbing toxicities. We recommend to restrict CE to patients with a life expectancy of more than 4-6 months confined to protocols, which evaluate efficacy, toxicity and influence on quality of life of CE with various cytotoxic drugs. We further suggest to perform staged unilobar CE at 4- to 6-week intervals rather than whole liver CE.

Adult↗
PubMed1992

Attempted prevention of blast crisis in chronic myeloid leukemia by the use of pulsed doses of cytarabine and lomustine. A Cancer and Leukemia Group B study.

An attempt to prevent the blast crisis in chronic myeloid leukemia by the use of pulsed doses of (cytarabine cytosine arabinoside) and lomustine was attempted as a cooperative group study by Cancer and Leukemia Group B. The basis for this study was to delay the development of blast crisis by pulsing dose of drugs known to be effective against emerging "blast" cells. The experimental arm which consisted of cytarabine and lomustine did not produce overall results superior to conventional treatment with busulfan. This was related to the non-hematologic effects of the combination which produced significant gastrointestinal toxicity leading to relatively early discontinuation of the combination. Nevertheless, the trial design allowed relatively prompt discontinuation of experimental arm and cross-over to conventional treatment with either hydrea or busulfan. No evidence existed that the use of new drug combinations in CML prejudiced the patient's chance to response to conventional chemotherapy. Thus, a role model for future trials in this disease was developed. With the development of the interferons and other experimental forms of therapy this conceptual development may be of significance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[The biochemical modulation of 5-fluorouracil by leucovorin].

5-fluorouracil (5-FU) is the most effective drug in the treatment of advanced colorectal carcinoma and has definite activity in a variety of other solid tumors. However, remissions occur in only about 20% of the patients and usually are of short duration. Biochemical modulation is a way of enhancing the efficacy of 5-FU by manipulation of intracellular metabolic pathways. Leucovorin (LV) prolongs the inhibition of the key enzyme, thymidylate synthetase, by stabilizing the ternary complex with activated 5-FU, thus leading to "thymidine-less" death. Phase II trials showed promising response rates in colorectal, gastric, and breast cancer. This translated into prolonged survival and into an increased therapeutic index in some phase III studies comparing the combination 5-FU/LV with 5-FU monotherapy in colorectal cancer. The present article focuses on the pharmacological background of the therapy with 5-FU/LV, summarizes the clinical data and gives a short overview on other ways of increasing the therapeutic index of 5-FU.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Structural studies of thiophilic N-chloroazasteroids.

N-Chloroazasteroids form covalent S-N bonds with thiol groups and so are of interest as chemoselective irreversible binding agents for the active sites of steroid receptors and enzymes. The solid-state structures of N-chloro-3-methoxy-17-aza-D-homo-1,3,5(10)-estratrien-16-one (1), N-chloro-3-methoxy-17-aza-D-homo-1,3,5(10)-estratrien-17a-on e (2) and N-chloro-3-methoxy-16-aza-1,3,5(10)-estratrien-17-one (3) were determined to obtain information about the spatial arrangement of the N-Cl groups. Crystal data: (1) C19H24ClNO2, Mr = 333.84, orthorhombic, P2l2l2l, a = 8.0190 (3), b = 12.7175 (5), c = 16.5047 (9) A, V = 1683.2 (1) A3, Z = 4, Dx = 1.317 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 20.9 cm-1, F(000) = 712, T = 295 K, R = 0.045 for 1786 observed reflections; (2) C19H24ClNO2, Mr = 333.84, orthorhombic, P2l2l2l, a = 10.9853 (7), b = 11.8216 (5), c = 12.9851 (9) A, V = 1686.3 (2) A3, Z = 4, Dx = 1.315 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 20.9 cm-1, F(000) = 712, T = 295 K, R = 0.035 for 1891 observed reflections; (3) C18H22ClNO2, Mr = 319.81, monoclinic, P2l, a = 13.246 (2), b = 7.972 (2), c = 7.696 (3) A, beta = 90.24 (2) degrees, V = 812.7 (4) A3, Z = 2, Dx = 1.307 g cm-3, lambda(Cu K alpha) = 1.54178 A, mu = 21.4 cm-1, F(000) = 340, T = 295 K, R = 0.045 for 1636 observed reflections.(ABSTRACT TRUNCATED AT 250 WORDS)

Azasteroids↗
PubMed1991

[Adjuvant therapies in breast carcinoma].

During the last two decades the treatment strategy in operable breast cancer has been revolutionized by the introduction of adjuvant systemic therapies. This article reviews the basis for the use of adjuvant systemic therapy and summarizes the results achieved so far. Practical guidelines are formulated.

Adult↗
PubMed1990

Effectiveness and low toxicity of hepatic artery infusion with fluorouracil and mitomycin for metastatic colorectal cancer confined to the liver. The Swiss Group for Clinical and Epidemiological Cancer Research (SAKK).

The usefulness of hepatic artery infusion (HAI) with floxuridine is limited by the severe biliary and hepatic toxicity of floxuridine. This prompted the SAKK to evaluate the effectiveness, toxicity and feasibility of HAI with fluorouracil (FU) and mitomycin (MMC) administered by an external portable pump. Of 28 patients treated, partial responses were obtained in 14 (50%, 95% confidence interval: 30% to 70%) and stabilization in 11 (39%, 21% to 60%), for a median duration of 12.6+ months. Median survival was 19.5+ months. Grade I-II toxicity (WHO) consisted of nausea (46%), leucopenia (32%) thrombocytopenia (21%) and abdominal discomfort (25%). Two patients developed gastro-duodenal ulcers and two others grade III leucopenia. No life-threatening side effects, especially no sclerosing cholangitis or chemical hepatitis, were observed. In conclusion, HAI with FU and MMC is a valid alternative to floxuridine HAI in metastatic colorectal cancer confined to the liver.

Adult↗
PubMed1989

[BRL 43694A--a 5-hydroxytryptamine receptor blocker as an antiemetic in cytostatic therapy].

An open study of the new antiemetic BRL 43694A, a 5-hydroxytryptamine-3-receptor antagonist, was performed in 29 patients undergoing highly emetogenic cancer chemotherapy (25 patients received cisplatin in a dose greater than or equal to 50 mg/m2). Patients received BRL 43694A as a 30-minute infusion one hour after the administration of chemotherapy. 7 patients were treated with 40 micrograms/kg and 13 patients with 100 micrograms/kg BRL 43694A; the last 9 patients received an initial dose of 40 micrograms/kg with a provision for two additional interventional doses over 24 hours in the event of prolonged nausea or vomiting. 14 patients experienced no vomiting (48%) and 13 patients (45%) had 1-5 vomiting episodes over 24 hours following administration of the cytostatic agents. BRL 43694A did not cause major side effects. Based on our preliminary experience the new 5-HT3-receptor antagonist BRL 43694A is a potent antiemetic drug for the treatment of chemotherapy-induced nausea and vomiting.

Adult↗
PubMed1989

[The vascularization of the intervertebral disks of the adult dog].

The (mainly lumbar) intervertebral discs of 21 recently euthanatized dogs (aged 3 days to 14 years) were examined grossly, under the dissection microscope and by light microscopy. The findings of the adult animals and the salient differences from the younger ones are reported. A few capillaries were observed in the outer 2-4 layers of the anulus fibrosus; these arose from segmental arteries that lay directly on the intervertebral discs. The principal supply of all intervertebral discs occurs by diffusion emanating from capillary loops. These are visible at 10-30 times enlargement in both unstained and benzidine stained preparations. They pass through the end plate of the vertebral body to where the bone gives way to the softer tissue of the disc. The capillary loops have wider lumina and are more numerous opposite the nucleus pulposus and in the adjacent perinuclear zone than more peripherally where the annular fibers attach to the bone.

Animals↗
PubMed1988

Vincristine and prednisone prolong the survival of patients receiving intravenous or oral melphalan for multiple myeloma: Cancer and Leukemia Group B experience.

A total of 589 patients with previously untreated multiple myeloma were randomized to receive daily oral melphalan, pulse-dose intravenous (IV) melphalan, carmustine (BCNU), or lomustine (CCNU). All patients received an initial tapering course of prednisone (Pred). During week 22 (day 154), patients were randomized to receive or not to receive additional therapy with vincristine (VCR) (1 mg/m2) and prednisone (0.6 mg/kg/d for seven days) at 8-week intervals. The influence of VCR/Pred was determined in 302 patients who remained on study beyond 22 weeks after initial therapy. VCR/Pred converted a significant percentage of nonresponders to responders in patients treated with melphalan (55% v 19%, P = .002), but not in patients treated with a nitrosourea (48% v 23%, P = .06). Survival beyond week 22 was significantly longer following the addition of VCR/Pred in patients receiving melphalan (median, 35.3 months v 27.0 months; P = .003) but not in patients receiving BCNU or CCNU (median, 28.1 months v 26.2 months; P = .91). These differences were seen both for oral and IV melphalan. A trend for beneficial effect of VCR/Pred was definitely seen in the good-risk patients (P = .03) but only suggestive for poor-risk patients (P = .12). Following adjustment for VCR/Pred effects, there were no differences in the survival of patients receiving any of the four initial treatments.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1979

[Pregnancy following tumor therapy].

A report is presented on 9 patients who became pregnant and gave birth to 11 children after intensive or long-term tumor therapy. Eight patients had Hodgkin's disease and one patient metastatic choriocarcinoma. Two children had a birth defect probably related to the anticancer therapy: one child has hearing loss of the inner ear and one child a cleft lip and palate. Some general issues relating to pregnancy after tumor therapy are discussed.

Abnormalities, Drug-Induced↗
PubMed1979

A comparative study of a BCNU containing 4-drug program versus MOPP versus 3-drug combinations in advanced Hodgkin's disease: a cooperative study by the Cancer and Leukemia Group B.

A prospective randomized trial by CALGB examined the relative value of four chemotherapy regimens in 537 patients with stage III B and IV Hodgkin's disease. A new combination BOPP, derived by substitution of BCNU for nitrogen mustard in the MOPP regimen, was compared to MOPP and to two 3-drug regimens, derived by removing the procarbazine in BOPP (BOP) or removing the alkylating agent (OPP). The 4-drug programs gave significantly higher frequency of complete remissions (BOPP 67%, MOPP 63%) than the 3-drug regimens (BOP 40%, OPP 42%), and significantly longer duration of remission and survival. BOPP had a therapeutic activity equal to MOPP, and was accompanied by less toxicity. After 6 cycles of induction chemotherapy, responding patients, both CR and PR, were continued on maintenance chemotherapy for 3 years. No significant difference in relapse rate was demonstrated following maintenance treatment with either vinblastine, chlorambucil, or chlorambucil plus monthly vincristine + prednisone doses. Nor could a reinforcement phase late in the maintenance program be shown to influence the relapse rate. The median survival for all patients entered on the 4-drug programs was 5 years, while the median has not yet been reached at 6 years for those patients, who obtained CR.

Adult↗
PubMed1978

[Evaluation program for cancer patients].

The medical evaluation and requisite radiologic examinations for the cancer patient are presented. Adequate clinical staging is essential for determining prognosis, optimal therapeutic plan, and evaluation of therapy results. Newer radiologic methods allow more detailed evaluation and determination of disease stage.

Bronchial Neoplasms↗
PubMed1978

[Interdisciplinary treatment planning in cancer].

The prerequisites for and purpose of optimal interdisciplinary cooperation in cancer treatment planning are presented from the viewpoint of the medical oncologist, the surgeon and the therapeutic radiologists. Only with full appreciation of the therapeutic possibilities offered by each individual treatment modality and speciality can an optimal interdisciplinary treatment plan be devised. This maximum of cooperation and interdisciplinary teamwork is also the basis for further progress and improvement of therapeutic results.

Breast Neoplasms↗
PubMed1976

[Prognostic factors concerning the survival time of Hodgkin's disease stage III and IV, treated with cytostatic agents].

On the basis of a retrospective study of 79 well-documented cases of Hodgkin's disease it has been possible to determine the prognostic significance of several factors in regard to 3-year survival. All patients evaluated were in stage III or IV and receiving polychemotherapy. According to the survival curves, the following factors adversely affected the prognosis to a significant extent: clinical stage IV, the presence of systemic symptoms, male sex, and failure to receive maintenance therapy. Also, patients treated by polychemotherapy only on relapse following other prior treatment, had a somewhat worse prognosis, though in out patient material this was not statistically significant. Other criteria significantly affecting the probability of 3-year survival in a negative sense were: decreased activity index, anemia, lymphopenia, elevated alkaline phosphatase values, low serum albumin and high serum globulin values. Elevated sedimentation rate, leukocytosis and leukopenia had no statistically significant influence upon survival.

Adolescent↗