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K W Brunner

Publications and source records attributed to K W Brunner.

At least 19 recordsLinked to original sources
PubMed2003

Adjuvant therapy after excision and radiation of isolated postmastectomy locoregional breast cancer recurrence: definitive results of a phase III randomized trial (SAKK 23/82) comparing tamoxifen with observation.

BACKGROUND: Adjuvant systemic treatment for patients with isolated locoregional recurrence (ILRR) of breast cancer is based on a single reported randomized trial. The trial, conducted by the Swiss Group for Clinical Cancer Research, compared tamoxifen (TAM) with observation after complete excision of the ILRR and proper radiotherapy. We performed a definitive analysis of treatment outcome at >11 years of follow-up, after the majority of the patients had a subsequent event of interest. Patient and methods One hundred and sixty-seven patients with 'good-risk' characteristics of disease were randomized. 'Good-risk' was defined as estrogen receptor expression in the ILRR, or having a disease-free interval of >12 months and a recurrence consisting of three or less tumor nodules, each </=3 cm in diameter. Seventy-nine percent of the patients were postmenopausal at randomization. RESULTS: The median follow-up time of the surviving patients was 11.6 years. The median post ILRR disease-free survival (DFS) was 6.5 years with TAM and 2.7 years with observation (P = 0.053). The difference was mainly due to reduction of further local relapses (P = 0.011). In postmenopausal patients, TAM led to an increase of DFS from 33% to 61% (P = 0.006). In premenopausal women, 5-year DFS was 60%, independent of TAM medication. For the whole study population, the median post-recurrence overall survival (OS) was 11.2 and 11.5 years in the observation and the TAM group, respectively; premenopausal patients experienced a 5-year OS of 90% for observation compared with 67% for TAM (P = 0.175), while the respective figures for postmenopausal patients were both 75%. CONCLUSIONS: These definitive results confirmed that TAM significantly improves the post-recurrence DFS of patients after local treatment for ILRR. This beneficial effect does not translate into a detectable OS advantage.

Adult↗
PubMed1994

Present and future projects of the International Breast Cancer Study Group.

The International Breast Cancer Study Group (formerly the Ludwig Group) has conducted nine clinical trials since 1978 (see the Appendix for participants and authors). Biologic hypotheses related to the combined use of chemotherapy and endocrine therapy in women with operable breast cancer were tested. Questions of timing of chemotherapy with respect to tumor surgery and late introduction of chemotherapy were also evaluated. Ongoing and future trials continue in this tradition to investigate combinations of available endocrine therapies and cytotoxic agents.

Aged↗
PubMed1993

Bioavailability and feasibility of subcutaneous 5-fluorouracil.

Continuous intravenous (i.v.) infusion of 5-fluorouracil (5-FU) has been shown to be superior to bolus regimens in terms of response rates and toxicity. However, a continuous infusion is more expensive and prone to complications such as thromboembolism and infections. A way to circumvent these problems would be to administer 5-FU subcutaneously (s.c.). To assess feasibility and bioavailability of s.c. 5-FU, eight patients with advanced cancer received 250 mg 5-FU as an infusion over 90 min either intravenously (i.v.) or s.c. into the abdominal wall. The mean +/- s.d. bioavailability of s.c. 5-FU was 0.89 +/- 0.23. The interpatient variability for the area under the plasma concentration-time curve was 48% for the s.c. and 36% for the i.v. infusion. No local side effects were observed. To test the local tolerance of a more prolonged administration three patients received 930-1,000 mg m-2 5-FU by 24-h continuous s.c. infusion. The steady-state plasma levels were comparable to i.v. infusion. One patient developed a painless skin pigmentation at the s.c. infusion site. However, the same reaction was observed at the forearm after i.v. infusion. We conclude that at the dose studied s.c. 5-FU has an almost complete bioavailability and is well tolerated. Further work will show, whether prolonged s.c. infusion can be used as a safe and economical alternative to i.v. infusion.

Adult↗
PubMed1993

Oral ondansetron in the prophylaxis of nausea and vomiting induced by cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in women with breast cancer. Results of a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: The combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) is a widely used chemotherapy regimen in breast cancer patients. However, the control of nausea and vomiting induced by oral CMF is a rarely examined problem. Therefore we felt a randomized, placebo controlled study justified in order to improve currently available antiemetic therapy. SUBJECTS AND METHODS: In a randomised double-blind trial ondansetron given orally, 8 mg three times a day for 15 days, was compared with placebo in 82 breast cancer patients receiving chemotherapy with CMF (cyclophosphamide 100 mg/m2 orally days 1-14, methotrexate 40 mg/m2 i.v. days 1 and 8 and 5-fluorouracil 600 mg/m2 i.v. days 1 and 8). The patients recorded nausea and the number of vomits and retches daily on diary cards. Forty-two patients received ondansetron and 40 received placebo. RESULTS: Significantly more patients who received ondansetron experienced neither vomiting nor retching (emesis) compared to those receiving placebo over a 15 day treatment period (60% vs. 35%, p = 0.027). The difference, with 95% confidence limits, was estimated at 25 (4.45%). Furthermore, there was a trend in favour of ondansetron in the control of nausea. Ondansetron was well tolerated, with 25 patients (59%) reporting at least 1 adverse event compared to 18 patients (45%) receiving placebo (p = 0.191). CONCLUSION: The results indicate that ondansetron given orally for 15 days is safe and effective in the control of emesis induced by CMF. It is however too early to recommend ondansetron as standard antiemetic therapy for oral CMF, as the treatment of nausea and vomiting in this setting has not been studied thoroughly enough.

Administration, Oral↗
PubMed1992

[Leiomyosarcoma of the breast 16 years following successful treatment of a rhabdomyosarcoma of the orbit in childhood].

A case of a mammary leiomyosarcoma in a 23-year-old woman is presented. The tumor appeared 16 years after successful treatment of an embryonal rhabdomyosarcoma of the orbit. Rhabdomyosarcomas are the most frequent soft tissue tumors of childhood, the orbit and the paratesticular region being the most common primary site for this tumor. In contrast, leiomyosarcomas other than those evolving from the viscera or the urogenital organs are rare neoplasms at any age. With the improvement of cancer treatment and survival rates, the risk of late effects after successful treatment for malignant tumors during childhood is increasing. Growth, development and fertility may be impaired and cosmetically disturbing facial and dental complications are common. Development of novel primary tumors is a known further consequence of successful treatment of brain tumors, retinoblastoma and acute leukemias. This is the case when high dose local radiation therapy and/or chemotherapy, especially alkylating agents, were used. Development of novel primary tumors is also known after treatment of childhood rhabdomyosarcomas. This report is intended to show that a second primary tumor may occur many years after a first successfully treated malignant neoplasm, and that young people are at risk for development of tumors at sites that are uncommon to this age group.

Adult↗
PubMed1992

Phase II study of continuous subcutaneous interferon-alfa combined with cisplatin in advanced malignant melanoma.

Interferon-alfa (IFN-alpha) and cisplatin have shown synergism in vitro against tumour cell lines and optimal effects were observed with continuous and high IFN concentration. 20 patients with advanced malignant melanoma were treated with 10 MU IFN subcutaneously continuously, daily, plus cisplatin 50 mg/m2 intravenously on days 8 and 9. Cisplatin was repeated every 4 weeks. The main toxic effects were myelosuppression, fatigue and weight loss. Toxicities always resolved completely after reduction/interruption of IFN and no life-threatening infection was observed. There were 1 complete and 6 partial responses. 6 patients had stable disease. Median time to progression was 7 months with a range of 16 to 2 months. The combined regimen of IFN-alpha and cisplatin is active in patients with multiple visceral and skeletal sites.

Adult↗
PubMed1991

[Syndrome of inappropriate ADH secretion (SIADH) in small-cell bronchus carcinoma].

Based upon the pertinent literature, the paraneoplastic syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with small cell lung cancer is reviewed. Small cell lung cancer is a distinct tumor with neuroendocrine features capable of producing peptide hormones amongst which the antidiuretic hormone (ADH, arginine vasopressin) is one of the most frequent. Paraneoplastic SIADH may result from ectopic ADH production or from other tumor-related mechanisms leading to increased pituitary ADH secretion. The overt SIADH is characterized by neurological and psychiatric symptoms attributable to cerebral edema. Pooled published data suggest that the average incidence of clinically manifest SIADH in patients with newly diagnosed small cell lung cancer is 4%. Cases without clinical symptoms, detectable by laboratory tests only, are more frequent: hyponatremia, serum hypoosmolality and urine hyperosmolality are present in 14%, and an inappropriately elevated level of immunoreactive ADH in 38% of all patients respectively. Successful treatment of the underlying tumor, accompanied by a restricted fluid intake in severe cases, will usually result in prompt disappearance of the paraneoplastic SIADH. During and after the tumor treatment, plasma ADH may be useful as a tumor marker.

Biomarkers, Tumor↗
PubMed1991

[Current developments in systemic therapy of breast carcinoma].

New developments in hormone- and chemotherapy of metastasizing breast cancer comprise replacement of ovariectomy by LH-RH antagonists in premenopausal women, new antiestrogens with less residual estrogenic activity for use mainly in postmenopausal patients as well as new potent inhibitors of aromatase with fewer adverse effects also for postmenopausal women. These new drugs will possibly provide better efficacy with fewer side effects, but at higher cost. In chemotherapy the search for more potent regimes continues. Experiments are under way with high-dose chemotherapy plans in conjunction with autologous bone marrow transplantation and hemopoietic growth factors; however, the result of these latter studies are so far disappointing. It has become clear that in nonaggressive metastasizing cancer of the breast high rates of remission seem not to be the ultimate goal. At this stage of disease the natural course is very heterogeneous; therefore, chemotherapy has to be adapted to risk. The goal must be improvement of quality of life for the remaining life-span by palliation of symptomatic disease while inducing as few side effects of treatment as possible. New; more potent chemotherapeutic agents are not at sight. Research has recently produced derivatives of already known agents producing fewer adverse effects at equal efficacy. Decisive for the choice of primary chemotherapy are prognostic indicators of the disease. For most cases, tumor specific therapeutic modalities have to be optimized.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Subcutaneous continuous infusion of ifosfamide and cyclophosphamide in ambulatory cancer patients: bioavailability and feasibility.

The oxazaphosphorines ifosfamide (IFO) and cyclophosphamide (CTX) are standard alkylating agents. Both drugs show an increased therapeutic index when given as a fractionated dosage over several days. Maximal fractionation is achieved by continuous infusion. We have studied the feasibility and bioavailability of a subcutaneously (s.c.) administered isotonic and neutral (pH 7) solution of IFO (10 h up to 5 days infusion) and CTX (12-24 h infusion) in patients with advanced cancer. A portable disposable gas-driven infusor syringe was used for ambulatory patients. Our results show 90%-100% bioavailability of s.c. IFO and CTX. The isotonic solution of IFO and CTX (pH 7) showed no significant local toxicity (one local infection in 51 cycles) during or after s.c. administration of 33 cycles with IFO and 18 with CTX. Haematotoxicity of both drugs was equal after s.c. and i.v. application. For IFO-treated patients no uro- or neurotoxicity was observed. We conclude that this novel continuous s.c. oxazaphosphorine infusion over a prolonged period is a rational, well-tolerated and economic way of delivering this drug on an outpatient basis.

Adult↗
PubMed1991

Continuous 5-day infusion of ifosfamide with mesna in inoperable pancreatic cancer patients: a phase II study.

Phase II studies on ifosfamide and mesna in pancreatic cancer have mostly been inconclusive. In all of these studies ifosfamide was administered as an i.v. bolus or by short infusions. Since dose fractionation of ifosfamide over several days increases its therapeutic index, we chose to maximize the dose fractioning by selecting a continuous-infusion schedule (1.75 g/m2 on days 1-5 every 21-28 days, with mesna 60%-100% of the ifosfamide dose up to 12 h after ifosfamide). Since 1987 29 patients (performance status less than or equal to 2) with advanced inoperable adenocarcinoma of the pancreas were studied (8 women and 21 men; median age 58 years: 36-73 years). A total of 25 patients are evaluable for response (1 ineligible; 3 inevaluable: 2 early deaths due to disseminated intravascular coagulation, 1 refusal). One female patient with a complete response on computed tomography scan (after five cycles) but residual liver metastases on surgical exploration survived for 473 days. Three male patients with partial response survived for 205, 335 and 355 days. Six more patients with minor response (3) or no change (3) but significant decrease of tumour marker CA 19-9 had a median survival of 213 days (106-243). Responders seemed to benefit in terms of pain relief and general well-being. The median overall survival of all patients was 148 days (21-473). Haematotoxicity was rarely dose-limiting [median nadirs: white blood cells = 2.1 x 10(9)/l (0.45-6.4), Hb = 10.7 g/dl (7.5-13), platelets = 137 x 10(9)/l (21-411)]. Nausea and vomiting were mild with prophylactic oral metoclopramide. No central nervous system toxicity or urotoxicity was observed. Alopecia was seen in all patients who had received at least two cycles. Continuous infusion of ifosfamide was generally well tolerated and useful for palliation in 10 of 25 patients. A higher dose intensity is recommended.

Adenocarcinoma↗
PubMed1990

[Goals, results and limitations of multimodal tumor therapy].

Multimodal tumor therapy, or the employment of two or more treatment modalities in combination, had led to several advances in the cure or long-term survival of patients with various tumor types. The individual established indications for multimodal tumor therapy are listed and described. Other indications remain controversial or are under evaluation in prospective randomized studies. In certain tumor types no advantage from the use of multimodal treatment has been demonstrated as yet. Aside from the advantages of multimodal therapy, the problems involved and possible side effects, especially in regard to short-, mid- and long-term toxic effects are described.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Bioavailability of subcutaneous ifosfamide and feasibility of continuous outpatient application in cancer patients.

The oxazaphosphorine prodrug Ifosfamide (IFO) in conjunction with the uroprotective agent Mesna is becoming a standard alkylating agent. It has an increased therapeutic index when given as a fractionated dosage over 3-5 days. Maximal fractionation is achieved by continuous infusion over several days and has been shown to be less emetic and neurotoxic than regimens with bolus infusions. We have studied in patients with advanced cancer the feasibility and bioavailability of a subcutaneously administered isotonic and neutral (pH 7) IFO solution given continuously over 10 h for up to 5 days. A portable disposable gas-driven infusor syringe was used. Our results show 90-100% bioavailability of sc administered IFO. The isotonic solution of IFO (pH 7) showed no significant local toxicity during or after sc administration. Haematotoxicity was equal for sc and iv application. No uro- or neurotoxicity has been observed in 24 sc cycles. We conclude that this novel continuous sc IFO infusion over several days is a rational, well-tolerated and economical way of delivering this drug on an outpatient basis.

Aged↗
PubMed1989

[Radioimmunoscintigraphy with a 99mTc-labeled F(ab')2 fragment of a monoclonal antibody (HMW-MAA 225.28S) in 71 patients with malignant melanoma].

In 71 patients with malignant melanoma 85 radioimmunoscintigraphies (RIS) with 99mTc-radiolabeled F(ab')2 fragments of a murine monoclonal antibody have been performed. The antibody is specific for an epitope of the HMW-MAA glycoprotein complex which is present in 90% of melanoma tissue samples. Sensitivity for RIS was 79% (73 metastatic sites out of a total of 92). 20 previously unknown lesions were found and there were also 2 false positives. Conventional staging procedures alone revealed 78% of the metastatic sites (72 of 92). No side effects were observed. RIS was especially useful for detection of lymph node metastases not found by conventional methods and is therefore considered complementary to conventional preoperative staging procedures.

Adult↗
PubMed1989

[Urinary bioavailability of sodium-2-mercaptoethanesulfonate (Uromitexan) following intravenous, subcutaneous and continuous subcutaneous administration].

The dose-limiting urotoxicity of the oxazaphosphorines (t1/2 = 4-15 h) is due to renal elimination of metabolites such as acrolein. The occurrence of hemorrhagic cystitis can be safely prevented by the concomitant use of i.v. or oral 2-mercaptoethanesulfonate sodium (DCI MESNA; Uromitexane). The bioavailability of oral MESNA is in the range of 20-50% and its unpleasant taste severely limits patient compliance. Due to the short half-life of MESNA (approx. 40 min) a regular fractionated or continuous administration is mandatory. In 6 healthy volunteers we have studied the pharmacokinetics of urinary MESNA elimination for the assessment of MESNA bioavailability after i.v. and s.c. drug administration. MESNA was given at doses of 400 mg for i.v. and s.c. bolus injections and 800 mg for continuous s.c. administration by a portable infusion pump. For the s.c. route an isotonic solution was prepared. The total amount of urinary thiols was assessed by the Ellman method (photometric reading at 412 nm). Total elimination of i.v. MESNA was 83.2 +/- 3.4% of the dose administered. The respective results for s.c. bolus and s.c. continuous drug administration were 81.9 +/- 3.4% and 79.4 +/- 3.6% of the dose. Continuous administration theoretically will provide optimal uroprotection from short term (hemorrhagic cystitis) and long term (bladder fibrosis and cancer) toxicity.

Biological Availability↗
PubMed1989

[Chemotherapy of bronchus carcinoma].

The use of chemotherapy will eventually be discussed in most patients with lung cancer, due to the systemic nature of the disease. In small cell lung cancer combination chemotherapy will achieve a response in the majority of patients and will lead to a five-fold increase in median survival. A small proportion of these patients will survive disease-free for a prolonged period of time and may be cured of their disease. In non-small cell lung cancer about one third of all patients will achieve an objective tumor response with the use of cisplatin-based combination chemotherapy. There is a small, but definite increase in median survival with the use of combination chemotherapy compared to best supportive care alone. Also in non-small cell lung cancer a small proportion of patients will survive after combination chemotherapy for a prolonged period of time. The use of cytotoxic treatment in lung cancer is associated with considerable toxicity so that optimal supportive care is mandatory.

Antineoplastic Combined Chemotherapy Protocols↗