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T Cerny

Publications and source records attributed to T Cerny.

124 records · Page 7Linked to original sources
PubMed1989

Prolongation of ifosfamide elimination half-life in obese patients due to altered drug distribution.

The pharmacokinetics of intravenous ifosfamide were determined in 16 patients with carcinoma of the bronchus. In all 25% (4) of these patients were obese (i.e. greater than 20% over their ideal body weight). The terminal elimination half-life (t1/2 beta) was found to be higher in the obese group than in the control group (6.36 h, range 5.77-7.45 h) vs 4.95 h, range 1.82-6.48 h) (P less than 0.05). This prolongation of the elimination half-life was due to an increased volume of distribution (Vd beta) in the obese group (42.81 1, range 35.49-51.90 l) vs 33.70 l range (17.76-50.62 l) (P less than 0.05). There was therefore no significant difference in total plasma clearance between the obese and normal groups. No correlation of ifosfamide plasma half-life was observed with total body weight (TBW) or ideal body weight (IBW). However, a significant positive correlation was observed between the percentage of IBW and plasma half-life. A strong positive correlation was observed between IBW and the plasma clearance of ifosfamide. The Vd beta correlated with both TBW and the percentage of IBW, but not with IBW itself. When Vd beta was normalised for IBW, there was a strong positive correlation with the percentage of IBW, suggesting that ifosfamide distribution into the TBW is higher than that into the IBW.

Adult↗
PubMed1989

Effect of in vivo administration of interferon gamma on expression of MHC products and tumour associated antigens in patients with metastatic melanoma.

IFN-gamma is an effective inducer of MHC class II antigen expression in cell lines of malignant melanoma. To investigate the possibility that IFN-gamma may increase MHC class I and II and melanoma tumour associated antigens in vivo, immunohistochemical analyses of biopsies from six patients with metastatic disease undergoing IFN-gamma treatment were performed. Before IFN-gamma treatment, the melanomas were class I positive and class II negative. After treatment, class I expression was neither enhanced nor class II expression induced in any tissue sample regardless of biopsy time or dose of IFN-gamma. TAA was similarly unchanged. However, in one of the six patients a primary cell line was established and IFN-gamma induced expression of MHC products. The possible reasons for lack of MHC induction are discussed, although qualitative changes in antigen expression cannot be excluded on the basis of qualitative immunocytochemical techniques alone.

Aged↗
PubMed1989

A simple outpatient treatment with oral ifosfamide and oral etoposide for patients with small cell lung cancer (SCLC).

For the first time in a clinical study oral Ifosfamide was used: 65 elderly or unfit patients with small cell lung cancer (SCLC) were treated as outpatients with fractionated oral Ifosfamide and Etoposide. Forty patients (62%) had extensive stage (ED) disease. The median age of the patients was 66 years. In the 60 patients evaluable for response the objective response rate was 90% with a complete response (CR) rate of 32% and a partial response (PR) rate of 58%. The overall median survival of all 65 patients was 11 months (13 months for LD, 9.5 months for ED). In those patients with LD achieving a CR or a PR radiotherapy was given to the mediastinum. No prophylactic cranial irradiation was given. There was a rapid improvement in the responding patients' performance status and symptoms generally with the first treatment cycle. Overall haematological toxicity was mild, with intravenous antibiotics only being required in 4% of the courses and with only one treatment-related death from septicaemia. A higher than expected rate of CNS toxicity was seen (30%). This was generally mild and always fully reversible and consisted mainly of forgetfulness, occasionally hallucinations, nightmares and somnolence. In only one case did encephalopathy necessitate early termination of treatment. This raises the question of whether Ifosfamide metabolism differs quantitatively or qualitatively when given by the oral route as opposed to the usual intravenous route. We conclude that this simple outpatient based treatment gives a high response rate with rapid improvement in symptoms.

Administration, Oral↗
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

[Involvement of the trachea and lungs in AIDS-associated Kaposi's sarcoma].

Kaposi's sarcoma is now the second most common AIDS-associated disease, Pneumocystis carinii pneumonia being the commonest. The clinical and radiological picture of bronchopulmonary Kaposi's sarcoma is often indistinguishable from that of nonspecific interstitial pneumonitis. Diagnosis of the sarcoma in the airways, and especially in the lung parenchyma, is difficult. The case of a patient with AIDS and bronchopulmonary Kaposi's sarcoma is presented and the diagnostic, therapeutic and prognostic problems are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Unexpected high toxicity in a phase II study of teniposide (VM-26) in elderly patients with untreated small cell lung cancer (SCLC).

Teniposide (VM 26) as a single agent has shown promising results in the treatment of patients with small cell lung cancer. We treated 32 (30 evaluable) non-pretreated elderly and poor prognosis patients with small cell lung cancer with teniposide 100 mg/day (30 min infusion) days 1-5, every 3-4 weeks. Overall initial performance status was poor (WHO 2 or 3 in 62%). Extensive disease (ED) was documented in 50% including five patients with CNS metastases all of whom received simultaneous cranial irradiation. There was an unexpected high early death rate of 30% (9/30) including five patients with early toxic death due to severe bone marrow suppression leading to fatal septicaemia. The overall response rate was only 33% with no complete response. Where appropriate non-responding or relapsing patients received second line treatment with multidrug regimens +/- radiotherapy. The overall median survival was 5.6 months [ED: 1.7, limited disease (LD): 7.5 months]. Median response duration was 5.4 months (ED: 5.1, LD: 6.7 months). For responding patients median survival was 8.8 months (ED) and 11.5 months (LD). We conclude that in elderly and poor performance status patients single agent teniposide as used in this study has an unacceptable high early death rate and that the response rate is inferior to modern standard multidrug regimens.

Aged↗
PubMed1987

Ifosfamide, etoposide, and thoracic irradiation therapy in 163 patients with unresectable small cell lung cancer.

One hundred sixty-three patients with small cell lung cancer were treated with six courses, at 3-week intervals, of ifosfamide (5 g/m2) with mesna and etoposide. Thoracic radiotherapy was delivered to the limited stage (LS) patients. The complete response rate (CR, determined clinically and radiologically) was 76% for the 78 LS patients with a further 14% partial response (PR). The majority of the CRs were confirmed on a follow-up bronchoscopy. The CR rate was 27% for extensive stage (ES) patients with another 38% undergoing a partial response. The median survival for LS patients was 11 months, (16 months for CR confirmed by rebronchoscopy) and 8 months for ES patients. The 2-year actuarial survival for LS patients is 27%, follow-up ranges from 12 months to 30 months with a median of 22 months. Toxicity was not severe for the patient population, of whom only 20% had a good performance status before chemotherapy. Parental antibiotics were required on 4% of all 844 chemotherapy courses and 12% of courses were delayed due to side effects. The majority of responses occurred within the first two courses of chemotherapy and there was a corresponding improvement in the patients' symptoms and performance status. The regimen produced rapid tumor response with corresponding improvement in symptoms without marked toxicity and allowed further treatment development.

Adult↗
PubMed1987

Pretreatment prognostic factors and scoring system in 407 small-cell lung cancer patients.

In 407 patients with small-cell lung cancer (SCLC), 61 pretreatment variables were evaluated in a Cox multiple regression analysis to assess their prognostic value. All patients received short-term intensive regimens (cyclophosphamide, etoposide and methotrexate or ifosfamide and etoposide, both followed by thoracic irradiation if complete response was noted). Lactate dehydrogenase (p = 0.001), tumour stage (p = 0.0001), serum sodium (p = 0.0009), pretreatment Karnofsky performance score (p = 0.0121), alkaline phosphatase (p = 0.0186) and serum bicarbonate (p = 0.0321) were the important prognostic factors. Once these variables were taken into account no other variable provided additional prognostic information. A simple scoring system ("Manchester Score") using these variables was established and shows little loss of information compared to the Cox analysis. The score distinguishes 3 prognostic groups, the best of which contains all long-term survivors, whereas the bad prognostic group contains no patient surviving longer than one year. The scoring system may help to design new treatment strategies and may also facilitate the comparison of different studies.

Carcinoma, Small Cell↗
PubMed1987

Immunoscintigraphy with 99mTc labelled F(ab')2 fragments of an anti melanoma monoclonal antibody (225.28S) in patients with metastatic malignant melanoma.

Immunoscintigraphy was performed in 25 patients with malignant melanoma using a 99mTc labelled monoclonal antibody (225.28S). In four cases, imaging was repeated following treatment with recombinant gamma interferon. In 11 cases, tissue samples of metastatic lesions were investigated for the expression of melanoma associated antigens by immunohistochemical techniques. Overall, 59% of known lesions were detected by imaging. The highest rates of detection were in bone, liver and lymph nodes and the lowest in lung, stomach and bowel. Six lesions were detected which had not shown up on routine clinical and radiological examination. There was no evidence of enhanced or induced HMW-MAA expression following interferon treatment. This technique has been found to be useful in staging patients and has been free from side effects.

Adult↗
PubMed1986

A simple quantitative HPLC assay for ifosfamide in biological fluids.

A high performance liquid chromatography method is described for measuring Ifosfamide (I) in human serum. This involves solvent extraction, reverse phase HPLC and UV detection at 190 nm. Standard curves of peak height x detector sensitivity versus I concentration in serum were linear with a lower limit of detection of 100 ng/ml. Authentic 14C-labelled I cochromatographed with standard I and with I found in serum from treated patients. The concentration-time curves of I determined by both HPLC and gas chromatography were indistinguishable. We conclude that this method is suitable for determining I pharmacokinetics in biological specimens.

Carbon Radioisotopes↗
PubMed1986

Bioavailability of ifosfamide in patients with bronchial carcinoma.

The pharmacokinetics of ifosfamide (I) were determined in ten patients with bronchogenic carcinoma. In seven patients, doses of 1 and 2 g (I) were given both as a bolus orally and later intravenously and were well tolerated. A further three patients received 5 g (I) as a single oral dose but in two this produced reversible CNS toxicity and severe vomiting. The area under the curve (AUC, microgram . h . l-1) for the 1-g dose was the same following oral and i.v. treatment and this was also true for the 2-g doses. There was a proportionate increase in the AUC for the 5-g oral dose, indicating 100% bioavailability at all three dose levels. We conclude that doses up to 2 g by mouth represent a well-tolerated alternative route of administration.

Administration, Oral↗
PubMed1986

Expression of epidermal growth factor receptor (EGF-R) in human lung tumours.

Epidermal growth factor receptor (EGF-R) expression was assessed in 63 lung tumour samples with a monoclonal antibody (EGF-R1) by indirect immunoperoxidase staining on cryostat sections. All 15 small cell lung cancer samples were negative whereas over 80% of the 48 non small lung cancer stained positively. In 30 bronchial biopsies two monoclonal antibodies against the cytoplasmic part of the EGF-R were evaluated. These antibodies showed weaker staining than EGF-R1. No additional or enhanced staining as compared with EGF-R1 was observed, suggesting a lack of enhanced expression of a truncated EGF-R analogous to the v-erb-B oncogene product. Monoclonal antibodies against the EGF-R may be helpful diagnostically in differentiating small cell from non small cell lung cancer and may also be important in elucidating biological differences in primary lung cancer.

Adenocarcinoma↗
PubMed1986

Genetic predisposition to human lung cancer.

The influence of polymorphic variants of the human c-Ha-ras gene on predisposition to lung cancer has been investigated. The human c-Ha-ras gene has been shown to reside on a polymorphic BamH1 restriction fragment. This restriction fragment length polymorphism (RFLP) results from variation in the size of a region of repetitive DNA 3' to the gene. An attempt has been made to characterise and compare the c-Ha-ras RFLP's in a normal population and in a group of cancer patients. DNA was extracted from the white blood cells of 101 normal donors and four common Ha-ras alleles identified, with occasional rare alleles of various sizes. The allele frequencies were examined in 132 lung cancer patients, comprising 66 individuals with small cell carcinoma of the lung (SCCL) and 66 with non-small cell carcinoma of the lung (non-SCCL). An abnormal allele distribution was found in individuals with non-SCCL compared to both control and SCCL values suggesting a degree of genetic pre-position to non-SCCL. In addition, analysis of the Ha-ras RFLP's in solid samples inferred a deletion of material from the short arm of chromosome 11 in two of 16 informative samples.

Adenocarcinoma↗
PubMedDate not supplied

Phase II studies of 4'-iodo-4'-deoxydoxorubicin in advanced non-small cell lung, colon and breast cancers.

The new anthracycline analogue, 4'-iodo-4'-deoxydoxorubicin (I-DOX), was administered at 70 mg/m2 as first chemotherapy in 61 patients with advanced NSCL (19), colon (20) and breast cancers (22). Treatment was repeated every 3 weeks; the dose was decreased to 60 mg/m2 (19% of the cycles) or increased to 80 mg/m2 (17% of the cycles) according to the granulocyte count nadir. Partial responses were observed in 6% of the patients with NSCL, in 5.5% of those with colon and in 10% of those with breast cancers. The main toxicity was a selective granulocytopenia characterized by a duration of about 1 week, and a high inter-patient variability. Non-haematological toxicities were mild. The negative results obtained in breast cancer might be related to the dose administered. Further studies in this tumour type should be performed with a more aggressive schedule.

Adult↗