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Biomedical subjects

T Cerny

Publications and source records attributed to T Cerny.

At least 91 records · Page 5Linked to original sources
PubMed1994

Docetaxel (Taxotere) is active in non-small-cell lung cancer: a phase II trial of the EORTC Early Clinical Trials Group (ECTG)

In a multicentre trial of the EORTC ECTG we have treated 43 non-pretreated patients with advanced non-small-cell lung cancer (NSCLC) with the new semisynthetic taxoid docetaxel (Taxotere). Six patients were ineligible; of the 37 eligible patients, ten had prior radiotherapy and 18 prior surgery. They received 100 mg m-2 in 1 h i.v. every 3 weeks, usually in an outpatient setting. Prophylactic steroids, antihistaminics or antiemetics were not routinely given. Two patients were not evaluable because they withdrew from the study because of a hypersensitivity reaction after the second cycle. The main toxicity was neutropenia (80% of cycles), although infections were rare (4%). One patient died from sepsis during neutropenia. Hypersensitivity reactions necessitating interruption of docetaxel (Taxotere) infusions were found in only 10% of cycles. The overall response rate was 23% with one complete response, and seven partial responses. Stable disease was found in 16 patients. The median duration of response was 36 weeks, and the median survival of all patients was 11 months. Docetaxel (Taxotere) is among the most active drugs for treatment of NSCLC.

Adult↗
PubMed1994

Randomized study of recombinant human granulocyte colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation for high-risk lymphoid malignancies.

PURPOSE: The aim of this prospective randomized trial was to examine the efficacy and safety of filgrastim after high-dose chemotherapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Patients with poor-risk non-Hodgkin's lymphoma or relapsed Hodgkin's disease were treated in a randomized, open-label trial to study the use of filgrastim as an adjunct to high-dose chemotherapy and ABMT. Of 43 assessable patients, 19 were randomized to receive filgrastim by continuous subcutaneous infusion at a dose of 10 micrograms/kg/d, 10 to filgrastim 20 micrograms/kg/d, and 14 to a parallel control group that received no filgrastim after ABMT. RESULTS: For all filgrastim-treated patients analyzed together, the median time to neutrophil recovery > or = 0.5 x 10(9)/L after the day of ABMT was significantly accelerated to 10 days compared with 18 days in control patients (P = .0001). The median number of platelet transfusions was identical in both groups. Clinical parameters, including the median number of days with fever (1 v 4, P = .0418) and neutropenic fever (5 v 13.5, P = .0001) were significantly shorter in the filgrastim than in the control group. The number of days on intravenous antibiotics and duration of hospitalization were also shorter in the treated groups; however, the differences did not reach statistical significance. For patients treated with the two different dose levels of filgrastim, the neutrophil recovery and clinical results were similar. Filgrastim-associated toxicity appeared to be minimal, with five adverse events considered at least possibly related to filgrastim: two in the higher-dose group and three in the lower-dose group. All of these were rated moderate, except one case of severe bone pain that did not preclude continued filgrastim treatment at a lower dose. Survival and relapse-free survival were similar for control and filgrastim-treated patients. CONCLUSION: Taken together, the results of this first randomized study support the role of filgrastim given as an adjunct to ABMT in accelerating neutrophil recovery, as well as in reducing treatment-related morbidity and overall duration of the treatment procedure.

Adolescent↗
PubMed1994

[Chemotherapy in lung carcinoma].

Lung cancer is still one of the main reasons for death in the western world. Its prevalence follows the pattern of smoking habits. Despite extensive research efforts there is still no break-through in systemic therapy of advanced lung cancer. Nevertheless, long-term survival has steadily been increasing during the last decades. This review is focussing on recent progress in treating non-small cell and small cell lung cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[Does non-conventional complementary therapies improve the quality of life of cancer patients? A critical literature review].

Despite substantial progress in biomedicine, a majority of advanced cancer diseases currently cannot be cured. In addition to conventional medical symptom management (palliation) and improvement of quality of life, methods of complementary medicine and supportive psychotherapy are increasingly applied. Whereas the efficacy of biomedical and psychotherapeutic interventions has been documented, controlled investigations of complementary methods are rare and their efficacy is poorly documented or is viewed controversially. Complementary methods are defined as methods applied by conventionally trained physicians and are based on tradition, or the perspective of human arts, which are not investigated or taught at universities. As an example of the latter, anthroposophic medicine is presented. Finally, we present a project developed within the scope of NFP 34, where the efficacy of a routine biomedical treatment is compared with an additional anthroposophic and psychotherapeutic intervention respectively.

Anthroposophy↗
PubMed1993

[Malignant lymphoma of the neck, nose and pharyngeal region].

Malignant lymphomas (Hodgkin's and Non Hodgkin's Lymphoma) are often diagnosed in lymphoid structures of the head and neck region as part of either a localized or an already disseminated disease. Its careful work-up with histology and accurate staging is the base of a successful therapeutic strategy. With appropriate chemotherapy and/or radiotherapy, the primary aim is often cure of disease. Other diseases important for differential diagnosis are discussed.

Adolescent↗
PubMed1993

Oral bioavailability of mesna tablets.

To test the feasibility of uroprotection with sodium 2-mercaptoethane-sulfonate (mesna) in tablet form the bioavailability of mesna tablets was determined in healthy volunteers by HPLC. The area under the plasma concentration-time curve (AUC) of free mesna was significantly lower following oral (110 mumol.l-1 x h-1; 95% CI 98-122) than following i.v. administration of 1.2 g of mesna (201 mumol.l-1 x h-1; 95% CI 158-244). The AUC for total mesna, i.e. dimesna and mixed disulfides, however, were comparable in the two groups, with 628 (539-717) and 772 (713-831) mumol.l-1 x h-1, respectively. The mean residence time was significantly longer following oral mesna, at 79 (76-83) min vs 239 (229-250) min. Following oral mesna 51.1% (46.2-56.0%) of the administered dose was recovered in the urine in 24 h, compared with 60.6 (53.6-67.6)% in 4 h following i.v. mesna, and the average concentration of mesna in the urine exceeded 3 mmol.l-1 for 8 h. The data indicate that mesna in tablet form has an adequate bioavailability for uroprotection and therefore may be preferable to liquid mesna, which has an unpleasant taste. Oral mesna has a longer mean residence time than i.v. mesna, which means that uroprotection can be achieved with longer dosing intervals.

Administration, Oral↗
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

Depletion of circulating cyst(e)ine by oral and intravenous mesna.

The sulfhydryl status of normal and tumour cells is critically important in determining their susceptibility to various cytostatic agents. As a sulfhydryl compound, mesna (sodium 2-mercaptoethane-sulfonate) which is used in large doses to prevent haemorrhagic cystitis associated with certain chemotherapeutic regimens might derange cellular thiol homeostasis. In order to investigate the effects of mesna on the concentrations of thiols in plasma, cysteine, glutathione and their disulfides were measured by HPLC following the oral and intravenous administration of mesna to healthy volunteers. After 7.3 mmol mesna i.v. free cysteine rose from 8.2 (95% CI 7.0-9.4) nmol ml-1 to 53.6 (47.4-59.8) nmol ml-1 at 5 min, most likely due to reduction of circulating cystine by the sulfhydryl drug. This initial rise was followed by a marked decrease of total cyst(e)ine in plasma from 276 (215-337) nmol ml-1 to a nadir of 102 (89-115) nmol ml-1 between 30-120 min after infusion, most likely due to an increased uptake of cysteine into cells and an increased urinary excretion of cyst(e)ine. Qualitatively similar changes were seen after oral mesna. The present data indicate that mesna depletes circulating cyst(e)ine and may thereby markedly alter the sulfhydryl status of cells in vivo although the drug itself is not taken up by most cells.

Administration, Oral↗
PubMed1993

Cytostatic drug resistance: parallel assessment of glutathione-based detoxifying enzymes, O6-alkylguanine-DNA-alkyltransferase and P-glycoprotein in adult patients with leukaemia.

The levels of several potential indicators of resistance to cytostatic drugs were measured in leukaemic cells of a total of 64 adult patients with acute or chronic leukaemias before and during treatment and at relapse or recurrence of disease and compared with those of mononuclear cells from the bone marrow of healthy donors. The resistance factors included glutathione (GSH) and its associated enzymes glutathione-S-transferase (GST) and glutathione peroxidase (GPx) as well as O6-alkyguanine-DNA-alkyltransferase (ATase) and P-glycoprotein. Median values for most parameters were significantly higher in leukaemic cells than in those of normal donors although wide interindividual variation in the values of the various parameters, particularly GST, were seen. P-glycoprotein was measurable in 12.5% of untreated leukaemias but in none of the normal donors. The values of the parameters in untreated leukaemic patients were not statistically different from those at relapse or during disease progression. However, the median values for GSH, GST and GPx but not ATase in samples from untreated patients were significantly higher than those in samples taken during drug treatment. Patient response, disease-free survival or duration of remission did not correlate with the values of any of the parameters studied.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Prevalence of the Rhesus-negative phenotype in Caucasian patients with small-cell lung cancer (SCLC).

We report that the Rhesus (Rh)-negative phenotype is more prevalent in patients with small-cell lung cancer (SCLC) than in the normal Caucasian population (SCLC: 25% Rh-negative vs. 15% expected, p less than 0.0001). This finding has been validated for a Central and a Northern European population (Switzerland and UK). In contrast, the Rh-negative phenotype is no more frequent in non-small-cell lung cancer patients or in heavy smokers with coronary heart disease than in the general population. There was a normal distribution of the ABO blood group phenotype in all patients studied. Whilst the significance of this observation is unclear, we hypothesize that a genetic predisposition to the development of SCLC may be linked to a hitherto unidentified gene on chromosome 1p near the Rh locus. Our observation may perhaps allow further progress to be made in understanding genetic mechanisms of SCLC carcinogenesis.

ABO Blood-Group System↗
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

Novel approaches with ifosfamide in small cell lung cancer.

During the past 5 years, ifosfamide has been used increasingly in combination chemotherapy for small cell lung cancer (SCLC). The high activity and favorable toxicity spectrum (with the uroprotector mesna) will encourage further use. A policy of no dosage reduction is feasible in patients receiving combination chemotherapy with ifosfamide given as a 24-hour intravenous (IV) infusion, which is much more convenient than the more commonly used 4- to 5-day fractionated regimen. This policy has resulted in actual 2-year survivals of 22% to 33% among SCLC patients not intensively staged. The stability of ifosfamide and its high bioavailability have allowed its use in chronic, 7-day ambulatory IV infusions, with decreased toxicity and hospitalization. Recently, oral and subcutaneous administration also have been tried, again allowing outpatient treatment. The first studies with hemopoietic growth factor support, eg, granulocyte colony-stimulating factor, conducted with combination chemotherapy with ifosfamide-containing regimens in SCLC, demonstrated significant reduction in neutropenia, infections, and antibiotic use. It is clear that the dosage of ifosfamide can be intensified in the future. The broad versatility of the drug will allow interesting new studies, including those to be conducted with outpatients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Palliative treatment of liver tumors].

Metastases of extrahepatic primaries are the most prevalent cause of malignant cells found in the liver. This overview is focusing on different regional and systemic palliative treatment modalities according to the histology of the primary tumor with special emphasis on metastastic colonic cancer. Furthermore indications and contraindications of the various treatment options are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
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

Assessment of P-glycoprotein, glutathione-based detoxifying enzymes and O6-alkylguanine-DNA alkyltransferase as potential indicators of constitutive drug resistance in human colorectal tumors.

Drug resistance is a major problem in cancer chemotherapy. Treatment protocols generally include a number of different cytotoxic drugs given in combination. Therefore, drug resistance in the tumor is likely to result from the coexpression of several cellular activities able to prevent cell killing by any of the drugs used. In this study we have measured several potential drug resistance mechanisms consisting of the multidrug resistance gene product P-glycoprotein, glutathione, glutathione-transferase and -peroxidase, and the DNA repair enzyme O6-alkylguanine-DNA-alkyltransferase in samples of colon carcinoma and normal adjacent mucosa from 23 untreated patients. All of these, with the exception of P-glycoprotein, showed significant increases in tumor tissue levels when compared with normal tissue from the same patient. The significance was highest for glutathione peroxidase (P less than or equal to 0.0005). Individual patients, however, showed very different patterns, with none, several, or all monitored resistance mechanisms elevated in the tumor. The implications both in the choice of drugs and in the use of resistance modifying agents to improve therapy for the individual patient are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗