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Biomedical subjects

K W Brunner

Publications and source records attributed to K W Brunner.

At least 19 recordsLinked to original sources
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↗
PubMed1989

[Immunoscintigraphy with 99mTc marked melanoma antibody in patients with malignant melanoma].

In 38 patients with malignant melanoma 44 radioimmunoscintigraphies (RIS) with 99mTc labeled F(ab')2 fragments of an anti-melanoma monoclonal antibody (225.28S, Tecnemab-K, Sorin Biomedica) have been performed. No side effects have been observed even in the patients with repeated RIS. Overall 81% (35/43) of all lesions were detected by imaging and 9 lesions have been previously unknown. Sensitivity and specificity was highest for lymphnode metastases with 100% each. Poor imaging was observed in lung and mediastinal metastases (2/7) as well as small skin metastases. RIS has to be studied for its clinical value in staging of lymphnode metastases preoperatively in patients undergoing regional lymphnode dissection.

Antibodies, Monoclonal↗
PubMed1988

[Loco-regional recurrence following surgery of breast carcinoma: prognostic factors and therapeutic consequences].

The course following local relapse after mastectomy was studied prospectively in 225 women. Factors significantly influencing the further course were determined. On the whole the prognosis was relatively good, with a projected 5-year relapse-free survival of 47%, a median time interval of 53 months until development of distant metastases, and an estimated death rate of 41% after 5 years. The most important factor influencing the incidence and time interval until appearance of distant metastases is the axillary lymph node status at the time of mastectomy. N0 patients have a much better prognosis than N+ patients in univariate as well as multivariate analysis. Other factors in univariate analysis which play a role in either the incidence of distant metastases or overall survival include estrogen receptor content, site of the local relapse (skin or regional lymph nodes), time interval between mastectomy and the occurrence of the local relapse, and number of tumor nodules in the local relapse. In multivariate analysis virtually the only really independent prognostic factors are primarily the initial axillary lymph node status for survival free of distant metastases and the time interval from mastectomy to local relapse for overall survival.

Breast Neoplasms↗
PubMed1988

Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy.

Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.

Abdomen↗