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Biomedical subjects

A P Lyss

Publications and source records attributed to A P Lyss.

At least 19 recordsLinked to original sources
PubMed1992

Intravenous 6-thioguanine or cisplatin, fluorouracil and leucovorin for advanced non-small cell lung cancer: a randomized phase II study of the cancer and leukemia group B.

This randomized phase II study was designed to evaluate the activity of intravenous 6-thioguanine (6-TG) as a single agent and the combination of cisplatin and 5-fluorouracil (5-Fu) modulated by oral leucovorin (PFL) in patients with advanced non-small cell lung cancer (NSCLC). Eligible patients had measurable or evaluable stage III B or IV NSCLC, had no received prior chemotherapy and had a performance status of 0-2. Patients were randomized to treatment with intravenous 6-TG at 55 mg/m2 administered over 30 minutes for 5 consecutive days and repeated every 35 days, or PFL chemotherapy with cisplatin 100 mg/m2 on day 1, 5-FU 800 mg/m2/day as a continuous intravenous infusion over 5 days and oral leucovorin administered at 100 mg every 4 hours during the entire duration of the cisplatin and 5-FU infusions. PFL was repeated every three weeks. Ninety-five eligible patients were randomized, 46 to 6-TG and 49 to PFL. Response rates were 4% for 6-TG (95% confidence interval 0.5%-14.8%, 1 partial, and 1 complete response) and 29% (16.6%-43.3%) for PFL (all partial). The median time to treatment failure was 2 and 4 months, respectively, and the median survival times were 6 and 10 months, respectively. Toxicities with 6-TG were, generally, mild to moderate but severe or life-threatening granulocytopenia was observed in 21% of patients. With PFL, mucositis was dose-limiting, and 78% of patients had severe or life-threatening mucositis. This led to dose reduction of 5-FU and leucovorin during subsequent cycles or treatment termination in 82% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Intensive etoposide and carboplatin chemotherapy for advanced non-small-cell lung cancer. A phase II trial of the Cancer and Leukemia Group B.

From April 2 to July 9, 1989, Cancer and Leukemia Group B (CALGB) conducted a Phase II study of etoposide and carboplatin in advanced (AJC Stage IIIb-IV) non-small-cell lung cancer (NSCLC) patients whose performance status (PS) was 0-2. The combination was given at the maximum tolerated dose as defined in a prior CALGB study. Of 76 eligible patients with follow-up data, complete responses were achieved in three patients (4%) and partial responses, in five patients (7%). One patient (1%) with evaluable disease showed improvement. There was only one partial response in the PS 2 patients. Performance status was a predictive factor for response or improvement (p = 0.0368). A high incidence (74%) of severe or life-threatening hematologic toxicity and fatal sepsis in four patients was a reflection of the intensity of the chemotherapeutic regime. The median survival from study entry was 7.4 months. Thirty-seven percent of the patients survived beyond 1 year; the median survival for the PS 0-1 patients was 11.7 months for the PS 2 patients, 4.1 months. Median time to treatment failure was 3.9 months, but treatment had not failed in 9% of the patients after 1 year, all of whom were PS 0-1 at time of study entry. Although the response rate with this dose-intensive chemotherapy regimen was disappointing, the median survival of PS 0-1 patients was equivalent to that of Stage III NSCLC patients in prior CALGB studies. In patients with NSCLC who are treated with chemotherapy, PS may be as important a prognostic factor as stage, when median survival is used as an endpoint.

Adult↗
PubMed1992

Evaluation of an implantable venous access system in a general oncology population.

Venous access has been a problem for the practicing oncologist. Previous approaches, such as arteriovenous fistulas, grafts, or percutaneous catheters, have not gained widespread acceptability. We report our experiences with 230 Port-a-Cath devices, a totally implantable venous access system. The catheters were placed in 218 general oncology patients for the administration of chemotherapy. One patient had three catheters placed and 10 patients had two catheters each. Most patients received standard bolus chemotherapy, while 25 patients were treated with continuous ambulatory infusions. The catheters were in place for an average of 271 days (range 2-1,427 days) for a total of 62,330 catheter days, representing the largest published experience with devices of this type in cancer patients. A total of 24 complications occurred in 22 patients. Catheter insertion was associated with four pneumothoraces, two of which required chest tube drainage. Five catheters were removed because of infection. There were 6 cases of venous thrombosis, but none resulted in pulmonary embolism. Other complications were manageable and included catheter occlusion, migration, and extravasation of chemotherapy agents. The Port-a-Cath is safe and is associated with a low rate of complications. Implantable venous access systems represent a significant advantage in the management of oncology patients with poor venous access.

Catheters, Indwelling↗
PubMed1992

Carboplatin in non-small cell lung cancer: an update on the Cancer and Leukemia Group B experience.

Since 1984, the Respiratory Committee of the Cancer and Leukemia Group B (CALGB) has evaluated carboplatin, either alone or in combination, in five separate phase II studies for patients with inoperable non-small cell lung cancer (NSCLC). All patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 and had not received previous treatment with chemotherapy. In 70 patients with stage IIIB or IV disease, carboplatin 400 mg/m2 administered intravenously once every 4 weeks produced a 16% overall response rate and an acceptable toxicity profile. Subsequently, combinations of carboplatin/cisplatin, carboplatin/etoposide, and carboplatin/vinblastine have been evaluated in similar patient groups. Response rates of 11%, 12%, and 20%, respectively, were obtained. Myelosuppressive toxicity was substantially greater with carboplatin/etoposide and carboplatin/vinblastine than with carboplatin alone. Carboplatin/vinblastine demonstrated efficacy similar to that of the cisplatin/vinblastine combination previously evaluated by CALGB for treatment of similar patients with advanced NSCLC; ease of administration and lack of significant nephrotoxicity also compared favorably with cisplatin-based therapy. In regional NSCLC patients, carboplatin 100 mg/m2/wk can be administered intravenously concurrently with 60 Gy thoracic radiotherapy given over 6 weeks. The impact of concurrent carboplatin added to a sequential chemotherapy-radiotherapy program for patients with regional NSCLC is currently under study by the CALGB Respiratory Committee.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

A simple method to estimate the initial dose of gentamicin.

A simple equation to estimate the initial dosing interval of gentamicin was compared with the "rule of eights" equation in 81 adult patients with stable renal function. The Sawchuk-Zaske method was employed as the standard with which dosing intervals estimated by the simple equation and the rule of eights method were compared. The actual mean peak gentamicin concentration was not significantly different from that predicted by the Sawchuk-Zaske method. The actual mean trough concentration was significantly higher than the predicted concentration, but trough concentrations within the usual therapeutic range of 0.5-2 microgram/ml were achieved in more than 90% of patients. The mean dosing interval calculated by Sawchuk-Zaske was not significantly different from that calculated by the equation, but was longer than the one calculated by the rule of eights. A peak gentamicin concentration within the usual therapeutic range was generally achieved with a total daily dose of 3-5 mg/kg of actual body weight. Until gentamicin concentrations are known, an easily remembered equation can be used to estimate the initial dosing interval for gentamicin. When used together with a standard total daily dose of 3-5 mg/kg total body weight, usual therapeutic concentrations are achieved in the majority of patients.

Adolescent↗
PubMed1991

Positron tomographic assessment of 16 alpha-[18F] fluoro-17 beta-estradiol uptake in metastatic breast carcinoma.

The positron-emitting estrogenic steroid 16 alpha-[18F]fluoro-17 beta-estradiol (FES) has been shown to exhibit selective uptake in primary breast carcinomas; the uptake of tracer by positron emission tomography (PET) is strongly correlated with the tumor estrogen-receptor concentration. We have now extended the use of this radiopharmaceutical for imaging of metastases of breast carcinoma by PET in 16 patients with clinical or radiographic evidence of metastatic disease. Increased uptake of FES was identified on PET images in 53 of 57 metastatic lesions (93%); only two apparent false-positive foci of FES uptake were seen. In seven of the patients, evaluable PET studies were obtained both before and after initiation of antiestrogen therapy. In all cases, there was a decrease in FES uptake in the tumor deposits after initiation of antiestrogen therapy, and the mean (+/- standard deviation) uptake decreased from 2.22 (+/- 1.23) to 0.80 (+/- 0.42) x 10(3)+ dose/ml. These results indicate that PET with FES has high sensitivity and specificity for detecting metastatic breast carcinoma and provide additional confirmatory evidence that the tumor uptake of this ligand is a receptor-mediated process.

Breast Neoplasms↗
PubMed1991

Management of soft tissue sarcomas of the extremities.

The management of soft tissue sarcomas has undergone and continues to undergo important changes. The purpose of this report is to review the presentation, diagnosis, and natural history of soft tissue sarcomas. In so doing, the importance of a careful and rigorous method of evaluation will be emphasized. Furthermore, the results of multidisciplinary treatment, with a goal towards limb salvage, will be reviewed. With appropriate and timely intervention, selected patients with pulmonary metastases may still experience long-term survival. Throughout this review, the importance of early and continuing multidisciplinary treatment and evaluation will be emphasized.

Arm↗
PubMed1989

Vindesine and mitomycin C in metastatic breast cancer. A Southeastern Cancer Study Group Trial.

64 eligible women with previously treated metastatic breast cancer received mitomycin C plus vindesine chemotherapy. Dosage was based on investigators' estimate of patients' bone marrow reserve. There were 19 evaluable patients in the good marrow reserve category, with two complete and three partial responses (26%). In the poor marrow reserve category there were 29 evaluable patients with four partial responses (14%). The 26% response rate in patients with good marrow reserve is consistent with results obtained with this and similar combinations by other investigators.

Adult↗
PubMed1988

Appendiceal malignancies.

Malignancies of the appendix are extremely rare. Of the reported cases, carcinoid tumors are most common, with mucinous cystadenocarcinomas and adenocarcinomas next in frequency. Adenocarcinoids, which share morphologic and clinical features that are a composite of adenocarcinomas and carcinoids, have been described. Concomitant second malignancies, most often in the GI tract, occur with greater than expected frequency in patients with appendiceal tumors. Treatment and prognosis are markedly different for each of the histologic variants of appendiceal malignancy. In general, carcinoid tumors (smaller than 2 cm in diameter) may be treated by appendectomy alone and are associated with long term survival. Adenocarcinomas, unless well differentiated and extremely superficial and localized, required hemicolectomy and confer a prognosis that is, stage for stage, similar to that of adenocarcinoma of the colon. Mucinous cystadenocarcinomas may spread widely through the abdomen, resulting in P peritonei, but can be associated with long survival duration if surgical treatment is aggressive. There is evidence that adenocarcinoids develop from simultaneous neoplastic change in two stem cell populations. Metastases may show histologic features of adenocarcinomas alone, of carcinoid tumors alone, or may resemble a composite neoplasm. The prognosis is variable and treatment recommendations are not well defined.

Adenocarcinoma↗
PubMed1987

Systemic treatment for prostate cancer.

Prostate cancer is a leading cause of cancer mortality in adult men. The majority of patients have subclinical systemic disease at diagnosis and will eventually require systemic therapy for palliation of symptoms. Recent development of new hormonal treatment options (e.g., gonadotropin-releasing hormone analogues and estramustine) has yet to demonstrate potential for improving the therapeutic index or for lengthening survival over results achieved with traditional modalities (i.e., supplemental estrogens or castration). Chemotherapeutic agents have demonstrated palliative efficacy and are being tested in multidrug regimens and in combination with hormones. At the present time, the optimal use of cytotoxic drugs remains undefined, since recently published studies have shown neither that combination chemotherapy is superior to single agents nor that chemo-hormonal therapy produces more favorable results than hormonal treatment alone.

Acid Phosphatase↗
PubMed1987

Reversibility of severe left ventricular dysfunction due to doxorubicin cardiotoxicity. Report of three cases.

Doxorubicin is a potent anticancer agent effective in a wide range of malignancies, but its use is limited by dose-dependent late cardiotoxicity. Severe doxorubicin cardiotoxicity has been associated with a poor prognosis and a high mortality rate, and until recently has been thought to be irreversible. We describe the cases of three patients with well-documented severe left ventricular dysfunction due to doxorubicin who had complete clinical recovery with return of cardiac function to normal. Because severe doxorubicin cardiotoxicity is reversible in some patients, aggressive supportive therapy is warranted.

Adult↗
PubMed1984

Chemotherapy of advanced breast cancer. A general survey.

Most patients with locally advanced primary breast cancer and almost all patients with disseminated malignancy will ultimately die of their disease. Nevertheless, because breast cancer is one of the most responsive of the solid tumors to cytotoxic drugs, appropriately chosen chemotherapy can relieve symptoms and prolong survival. Adriamycin (doxorubicin) is the most effective among many useful single agents. Combination chemotherapy can augment responses with acceptable toxicity and, along with hormonal manipulation in selected situations, constitutes the standard of care for metastatic disease in 1983. In the interpretation of the clinical oncology literature, meticulous attention to prognostic factors and details of study design is necessary in order to assess the superiority of any particular regimen. Controlled clinical trials of various drug combinations and schedules are especially valuable. The use of an integrated clinical approach involving rational surgical, radiologic, and medical strategies in the management of locally advanced as well as metastatic breast cancer can provide not only meaningful palliation but prolonged disease-free survival for many patients with this common neoplasm.

Antineoplastic Agents↗
PubMed1984

Ph1-positive acute leukemia with a 17q;21q translocation.

Chromosome studies on the neoplastic cells of an adult patient with poorly differentiated acute leukemia revealed two Ph1-positive subpopulations, with and without a 17q;21q (q22;q22) translocation. The breakpoints appeared to be the same as in the 8;21 and 15;17 translocations of acute mytelogenous leukemia (AML) and acute promyelocytic leukemia (APL), emphasizing the significance of rearrangements involving these sites in the pathogenesis of acute leukemia. Terminally, there was clonal evolution, with the new predominant subline having an additional translocation, 1q;19q, resulting in trisomy for most of 1q and, apparently, additional selective advantage.

Adult↗
PubMed1984

Presence of complement-fixing anti-endothelial cell antibodies in systemic lupus erythematosus.

Vasculitis in systemic lupus erythematosus (SLE) is associated with the deposition of IgG and complement in blood vessel walls. However, it is not known whether immune injury to endothelial cells is a part of this process. Therefore, we used a solid phase radioimmunoassay to study the ability of IgG from normal human sera and sera from patients with SLE to bind to endothelial cells. In this assay, cultured human umbilical venous endothelial cells were sequentially incubated with normal or SLE sera, goat anti-human IgG, and 125I-labeled staphylococcal protein A (*SPA). After exposure to normal sera, 2.5 +/- 0.5% (mean +/- SD) of the added *SPA bound to the cells, whereas after exposure to SLE sera 13.8 +/- 7.6% of the added *SPA bound to these cells. This difference in binding was highly significant (P less than 0.001). Binding was partially reduced when SLE sera were preincubated with B-lymphocytes or monocytes, but not after exposure to erythrocytes, platelets, or T lymphocytes. Incubation of endothelial cells with the 7S fraction of SLE sera or with the F(ab')2 fragment of SLE-IgG resulted in the deposition of greater than 80% as much IgG as was deposited on endothelial cells by whole serum. However, since higher molecular weight fractions (greater than 7S) of SLE sera were also active, we tested the capacity of endothelial cells to bind IgG complexes. Endothelial cells bound heat-aggregated IgG (HA-IgG) in a saturable manner at one log concentration below the binding of normal monomeric IgG. Binding of HA-IgG to endothelial cells was markedly enhanced by preincubation with a serum source of complement. Both HA-IgG and SLE-IgG also bound to freshly obtained endothelial cells in suspension, as detected by automated fluorescence flow cytometry. Binding of SLE-IgG and HA-IgG to endothelium initiated complement activation, deposition of the third component of complement, and disruption of the monolayer. In addition, SLE-IgG and HA-IgG caused endothelial cells to secrete prostacyclin and caused the adherence of platelets, confirmed by scanning electron microscopy. These studies demonstrate that IgG anti-endothelial antibodies are present in the sera of patients with active SLE. These sera may also contain IgG complexes that are capable of binding to endothelial cells. The association of IgG and complement with endothelial cells may initiate vascular injury in SLE and other human disorders.

Antibody Specificity↗
PubMed1982

Fc and C3 receptors induced by herpes simplex virus on cultured human endothelial cells.

The mechanism by which immune complexes deposit in vascular tissue is uncertain. Several human viruses, including herpes simplex virus, have recently been demonstrated to replicate in human endothelial cells. Such viruses may injure vascular tissue and could play a role in the pathogenesis of immune complex deposition. Therefore, we studied the expression of receptors for immune complexes containing IgG and C3 on endothelial cells after infection with herpes simplex virus type I.Human umbilical vein endothelial cells were incubated with (51)Cr-labeled sheep erythrocytes sensitized with IgG, IgM, or IgM plus complement. Preferential binding of IgG or complement-coated erythrocytes to uninfected endothelial monolayers was not observed. In contrast, significant binding of erythrocytes coated with IgG or IgM plus complement was observed after viral infection. Phase-contrast and scanning electron microscopy demonstrated erythrocyte adherence around the infected endothelial cells in a rosette pattern. Binding of IgG-coated erythrocytes was fully inhibited by Fc (0.31 mg/ml) but not Fab' fragments of nonimmune IgG. Binding of complement-coated cells was unaffected by the presence of IgG (1 mg/ml). With purified individual components, binding of complement-coated erythrocytes depended on the presence and was proportional to the concentration of C3. Binding of IgG-or C3-coated cells was detected beginning 4 h after infection. These studies indicate that herpes simplex virus type I infection can induce IgG and C3 receptors on human endothelial cells. These receptors may promote the deposition of immune complexes in vascular tissue after certain viral infections.

Culture Techniques↗