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Biomedical subjects

J Klastersky

Publications and source records attributed to J Klastersky.

At least 199 records · Page 11Linked to original sources
PubMed1986

Emergence of resistance as a consequence of antimicrobial prophylaxis in immunocompromised patients.

Many authors in the literature have investigated the use of antibiotics in prophylaxis against infections in granulocytopenic patients. Two general methods have been used: one consists in trying to decontaminate the digestive tract in the hope of reducing the amount of microorganisms responsible for systemic infections. Another method is to use well-absorbed oral antibiotics, like trimethoprim-sulphamethoxazole, throughout the neutropenic period. It is considered critical to preserve as much as possible of the anaerobic flora, which is believed to provide protection against colonization by aerobic microorganisms or by fungi. Experimental and clinical evidence for this is critically reviewed. The efficacy of such methods has been variable, but there is also widespread fears that they could enhance selection of resistant organisms. We have reviewed the literature, specifically looking for data on the emergence of such resistant organisms, as well as data on changes in bacterial and fungal faecal flora.

Agranulocytosis↗
PubMed1986

Combination chemotherapy with mitomycin and vindesine in advanced non-small cell lung cancer: a pilot study by the Lung Cancer Working Party (Belgium).

The combination of mitomycin plus vindesine in advanced non-small cell lung cancer induced an objective response rate of 23% in 43 evaluable patients: 33% in nonpretreated patients (nine responses among 27 patients) and 6% in pretreated patients (one response among 16 patients). Toxicity was tolerable. We conclude that the regimen was a moderately active and easy to administer treatment for advanced non-small cell lung cancer.

Adult↗
PubMed1985

Combination chemotherapy with adriamycin, etoposide, and cyclophosphamide for small cell carcinoma of the lung. A study by the EORTC Lung Cancer Working Party (Belgium).

The current study reports the results of Adriamycin (doxorubicin), etoposide, and cyclophosphamide (AVE) in small cell bronchogenic carcinoma. The overall rate of response was 82% in patients with limited disease and 66% in patients with extensive disease; complete remissions have been achieved in 20% of the patients with limited disease and in 7% of those with extensive disease. The median duration of survival was 14 months in patients with limited disease and 8.3 months in those with extensive disease. The results, and the analysis of literature, suggest that survival rather than response should be used to compare studies of chemotherapy in small cell bronchogenic carcinoma.

Adult↗
PubMed1985

Complete remissions in non small cell lung cancer.

We studied 241 patients with non small cell bronchogenic cancer who were treated with cisplatin and etoposide or cisplatin, etoposide and vindesine. There were 11 (4.5%) complete responders in these series most of whom had a prolonged survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Phase II study of ametantrone in a human tumor cloning assay.

The anticancer activity of ametantrone was investigated in a human tumor cloning assay. Tumor samples were freshly obtained from 105 patients. Cells were exposed for 1 hr to drug concentrations of 1 and 10 micrograms/ml. A reduction in the number of tumor colony-forming units by 50% or more was seen in 2/31 breast cancers, 2/25 ovarian cancers, 1/10 primaries of unknown origin, 1/10 melanomas, 2/8 non-small cell lung cancers, 1/5 small cell lung cancers and 1/3 colon cancers. Only three of these in vitro responses were consistently obtained at the probably more relevant concentration of 1 microgram/ml. These findings indicate that low efficacy should be expected in cancer patients with ametantrone. The predictive value of these in vitro phase II data remains to be demonstrated.

Anthraquinones↗
PubMed1985

Comparative in-vitro activities of azlocillin, ticarcillin and ticarcillin plus clavulanic acid against Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa.

Azlocillin (5 g), ticarcillin (5 g) and ticarcillin (5 g) plus clavulanic acid (200 mg) were administered intravenously on separate days to human volunteers. Serum levels 1 h after the infusion were (mean +/- S.E.): 263 +/- 40 mg/1 for azlocillin, 238 +/- 56 mg/l for ticarcillin and 5.5 +/- 1.9 mg/l for clavulanic acid. Serum withdrawn at 0.5 h was titrated against ten strains of Staphylococcus aureus, ten Klebsiella pneumoniae and nine Pseudomonas aeruginosa of which four were resistant to ticarcillin. Against Staph. aureus and K. pneumoniae, median serum bactericidal activity (SBA) and percentage of sera with SBA greater than or equal to 1:8 were greater with ticarcillin plus clavulanic acid (median SBA 1:32 and 85% of sera with SBA greater than or equal to 1:8) than with the other two regimens. There were no differences in activity against Ps. aeruginosa.

Azlocillin↗
PubMed1985

Bactericidal activity of ciprofloxacin in serum and urine against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus faecalis.

Ten volunteers received three doses of 500 mg ciprofloxacin, orally every 12 hours. After the last dose, mean serum levels were (mg/l +/- SD) 2.4 +/- 0.83 at 1 h; 0.91 +/- 0.30 at 4 h and 0.18 +/- 0.04 at 12 h. At 1 h the median serum bactericidal activity was satisfactory only against the Escherichia coli (1:256) and Klebsiella pneumoniae (1:128). In urine collected from 0 to 4 h and 8 to 12 h after the last dose, the mean ciprofloxacin level was respectively 482.5 +/- 324.7 and 80.9 +/- 48.2 mg/l +/- SD. Bactericidal activity in urine was high even against the least susceptible species tested: Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus faecalis. A post antibiotic effect was demonstrated in 22 out of the 29 strains tested, ranging mainly from 1 to 3 h. Ciprofloxacin 500 mg orally twice a day is a bactericidal regimen against a wide range of urinary pathogens but has a limited systemic activity.

Bacteria↗
PubMed1985

Double-blind, placebo-controlled study of oxacillin combined with rifampin in the treatment of staphylococcal infections.

A total of 101 patients with proven Staphylococcus aureus infection were included in a double-blind, placebo-controlled study; this study compared oxacillin (12 g/day, intravenously) or vancomycin (2 g/day, intravenously) plus rifampin (1,200 mg/day, orally) with oxacillin or vancomycin plus placebo. We evaluated 65 patients. Of the patients tested, 33 received oxacillin plus rifampin (13 bacteremias), and 32 received oxacillin plus placebo (16 bacteremias). Clinical cure was achieved in 61% of the patients treated with oxacillin plus rifampin and in 56% of the patients treated with oxacillin plus placebo. Improvement was noted in 27 and 25%, respectively, and failure occurred in 9 and 18%, respectively. These differences were not statistically significant. Bacteriological failure occurred in 3 and 28%, respectively (P less than 0.05). None of the failures within the rifampin-treated group was associated with the emergence of a rifampin-resistant mutant. The rates of superinfection were similar in both groups. The geometric means of the serum bactericidal activity after 1, 6, and 11 h were, respectively, 22, 17, and 9 after treatment with oxacillin plus rifampin and 25, 3.4, and 2.3 after treatment with oxacillin plus placebo. It was suggested that the addition of rifampin to oxacillin or vancomycin might only be beneficial to severely ill patients.

Blood Bactericidal Activity↗
PubMed1985

Late intensification in small-cell lung cancer: a phase I study of high doses of cyclophosphamide and etoposide with autologous bone marrow transplantation.

We conducted a late dose intensification pilot study of small-cell lung cancer (SCLC) treated with high doses of cyclophosphamide (200 mg/kg) and etoposide (1.0 to 3.5 g/m2), administered during a period of 48 hours, as well as autologous bone marrow infusion. We have been able to administer safely 3 g/m2 of etoposide with the autologous bone marrow infusion and 1.5 g/m2 without it. Limiting extrahematopoietic toxicity appeared to take the form of irreversible cardiac failure. Complete responses have been obtained with our regimen for late dose intensification, but the duration of the responses and the survival rates of the patients were poor. This suggests that late dose intensification in incomplete responders is not superior to the usually reported results obtained with standard regimens for the treatment of SCLC.

Adrenal Gland Neoplasms↗
PubMed1985

Infections in immunocompromised patients. I. Pathogenesis, etiology, and diagnosis.

Granulocytopenia is the major factor predisposing cancer patients to infection, chiefly by bacteria. Most of the infections are caused by gram-negative aerobic organisms (Escherichia coli, Pseudomonas aeruginosa, and Klebsiella sp) that arise from endogenous gastrointestinal, mucosal, or cutaneous flora (often modified by hospital-acquired pathogens). Some fungi (Candida sp and Aspergillus sp) are also likely to invade granulocytopenic patients. The next most important factor predisposing cancer patients to infection is alteration of anatomic barriers. Mucosal and skin protection is compromised by tumors, radiotherapy, chemotherapy, surgical diagnostic and therapeutic procedures, and intravenous lines and other devices. The pathogens found in cases of altered anatomical barriers are similar to those encountered in patients with granulocytopenia, which is a major cause of alteration of anatomical barriers. The third factor predisposing patients to serious bacterial and nonbacterial infections is immunosuppression, especially in patients with lymphomas, multiple myelomas, and chronic lymphatic leukemia. The pathogens isolated in these patients include Listeria monocytogenes, Salmonella sp, Brucella sp, Mycobacterium sp, and Nocardia asteroides, although P aeruginosa and staphylococci may be found as well. Viruses (herpes simplex, herpes zoster, and vaccinia), parasites, fungi, and Pneumocystis carinii and Toxoplasma gondii are involved in many infections in these patients, in whom cell-mediated immunity is impaired. In neutropenic patients, antimicrobial or antifungal therapy should be instituted before the microbiological diagnosis is made; in immunosuppressed patients, therapy is optimally guided by a specific microbiological diagnosis.

Agranulocytosis↗
PubMed1985

Chemotherapy of non-small-cell lung cancer.

Cisplatin (Platinol)-containing regimens, especially in combination with etoposide (VP-16) (VePesid), vindesine, and/or mitomycin-C, have proven beneficial to patients with non-small-cell lung cancer. A reproducible response rate of 30% to 40% has been achieved. Because current therapies are greatly in need of improvement, patients with non-small-cell lung cancer--especially those who have a good performance status and thus are more likely to respond--should be considered for participation in clinical studies in which the control regimens are associated with moderate response rates. Although chemotherapy affords some benefit to nonresponding patients, they might participate in phase I or phase II trials rather than continue treatment more likely to be toxic than beneficial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

VP-16 and cisplatin in the treatment of non-small-cell lung cancer.

The EORTC Lung Cancer Working Party investigated the effects of combination therapy with VP-16 (Ve-Pesid) and cisplatin in the treatment of non-small-cell lung cancer (NSCLC). Neither agent alone is recognized as being associated with a high rate of response in NSCLC, but the combination proved beneficial in our hands and effected a total response rate (including complete and partial responses) of over 40%. In addition to this encouraging result, complete remissions occurred in a modest number of patients. The addition of vindesine to the regimen profferred no benefit, but did increase the incidence of toxic reactions. Preliminary data on supraconventional dosages of cisplatin indicate a trend toward better response and longer survival but a significantly higher frequency of severe leukopenia as well. No studies have yet been conducted with higher doses of VP-16 in NSCLC patients, but related investigations into the treatment of small-cell bronchogenic carcinoma indicated that doses up to 3 g/m2 of VP-16 were well tolerated by patients. It is cautiously concluded that the combination of cisplatin and VP-16 probably offers an advantage over single-drug therapy with either agent alone in the treatment of non-small-cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗