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Biomedical subjects

J Klastersky

Publications and source records attributed to J Klastersky.

At least 109 records · Page 6Linked to original sources
PubMed1991

Prospective randomized evaluation of ciprofloxacin versus piperacillin plus amikacin for empiric antibiotic therapy of febrile granulocytopenic cancer patients with lymphomas and solid tumors. The European Organization for Research on Treatment of Cancer International Antimicrobial Therapy Cooperative Group.

Empiric therapy for febrile granulocytopenic patients is mandatory, but whether monotherapy is a safe alternative and whether fluoroquinolones are useful agents for this indication are still controversial issues. The use of monotherapy with intravenous ciprofloxacin (200 to 300 mg every 12 h) was evaluated against combined therapy with piperacillin plus amikacin in febrile granulocytopenic patients with solid tumor or lymphoma. The study was discontinued prematurely because patients treated with ciprofloxacin had a significantly lower overall success rate than patients treated with piperacillin plus amikacin (31 of 48 patients [65%] versus 48 of 53 patients [91%], P = 0.002). Patients with gram-positive coccal bacteremia had a particularly poor outcome: therapy failed for six of eight patients (75%) treated with ciprofloxacin, while therapy failed for none of four patients treated with piperacillin plus amikacin. Death from primary infection during initially randomized protocol therapy occurred in 7 of 48 patients (14.5%) treated with ciprofloxacin and in 3 of 53 (6%) treated with piperacillin plus amikacin. This study does not support the use of this dose of intravenous ciprofloxacin as empiric monotherapy for fever in granulocytopenic patients.

Adult↗
PubMed1991

Drug treatment of pneumonia in the hospital. What are the choices?

Mortality and morbidity of nosocomial pneumonia remain high. Successful treatment of pulmonary infections depends on several factors including type of infection, offending pathogen, status of host defences, and adequate choice of antibiotic therapy. The physician's decision should aim at achieving antibiotic concentrations beyond the MIC at the site of infection. Gram-negative bacilli, notably Pseudomonos aeruginosa, Klebsiella pneumoniae and Escherichia coli, remain the most frequent agents in nosocomial pneumonia. Staphylococcus aureus and Streptococcus pneumoniae predominate among the Gram-positive cocci. Pneumocystis carinii predominates in immunocompromised patients. Protected sample bronchoscopy associated with quantitative cultures of samples, and quantification of intracellular microorganisms in cells recovered by broncho-alveolar lavage are two promising procedures which might replace previous, more aggressive methods. Penetration of antibiotics into lung tissue depends on physicochemical properties of the drug and the degree of inflammation of lung tissue. Quinolones, macrolides, tetracyclines and trimethoprim penetrate well into bronchial secretions. Penetration is moderate to low for aminoglycosides and beta-lactams. Fluoroquinolones and new beta-lactam agents, including third-generation cephalosporins imipenem, aztreonam and ticarcillin-clavulanate, showed comparative clinical efficacy in treatment of nosocomial pneumonia, with an efficacy rate close to 80%. Aminoglycosides should not be used alone. Combination therapy reduces but does not eliminate the risk of selection of Gram-negative resistant mutants. It should not be used routinely except for P. aeruginosa, Enterobacter cloacae and Serratia marcescens infections.

Anti-Bacterial Agents↗
PubMed1991

Secondary neoplasms following cancer treatment with a special emphasis on lung tumors.

In patients with successfully treated Hodgkin's disease, lung cancers, and particularly small cell lung cancers, are not uncommon (relative risk: +/- 5) and result essentially from radiotherapy. What is usually considered as a late recurrence of small cell lung cancer occurs also frequently in long-term surviving patients after therapy for small cell lung cancer; it is hypothesized that at least some of these tumors might be in fact induced by the therapy used for the initial lung neoplasm.

Antineoplastic Agents↗
PubMed1990

Study of the influence of protein binding on serum bactericidal titres and killing rates in volunteers receiving ceftazidime, cefotaxime and ceftriaxone.

The influence of protein binding on anti-staphylococcal activity of cefotaxime, ceftazidime and ceftriaxone was evaluated using an ex vivo cross-over study in human volunteers. Serum inhibitory and bactericidal titres were measured using samples collected 1 h and 6 h after infusion of 2 g of cefotaxime and ceftazidime and 1 g of ceftriaxone. Time-kill curves were done using the same samples. Twelve strains of Staphylococcus aureus were studied including six capsulated strains of known capsule types. Two media were compared: Mueller-Hinton and 'capsule' medium. The MICs and MBCs of oxacillin-susceptible strains measured in capsule medium were higher than in Mueller-Hinton, hence the higher serum inhibitory and bactericidal titres in the latter medium. The effect of protein binding was evaluated, using the difference between expected serum titres, from serum concentration and MICs or MBCs measured in serum-free medium, and the area under the time-kill curve corrected for the serum concentration and the sensitivity of the strains. The anti-staphylococcal activity of ceftriaxone was markedly affected by its strong protein binding.

Adult↗
PubMed1990

Validation of clinical predictive value of in vitro colorimetric chemosensitivity assay in head and neck cancer.

For chemosensitivity testing, a rapid in vitro colorimetric method (MTT assay) was used. Eleven head and neck cancer cell lines were investigated to distinguish five known active agents from five compounds inactive in phase II studies. Evaluation of the reliability of the assay for assessing drug sensitivity in this tumor cell population was done by correlating the in vitro results with reported in vivo response data. Methotrexate and cisplatin (clinically active) and vindesine and doxorubicin (less active clinically) were recognized in vitro as active and correlated well with clinical experience. Bleomycin (clinically active) was ineffective against some cell lines. The in vitro findings for the clinically inactive drugs (deoxyazacytidine, lomustine, and carmustine) also corresponded. Amsacrine and etoposide, contrary to clinical experience, showed activity in vitro. Further comparison of MTT assay results with clinical data is warranted and essential before its use in large-scale drug screening studies.

Antineoplastic Agents↗
PubMed1990

A randomized study comparing etoposide and vindesine with or without cisplatin as induction therapy for small cell lung cancer. EORTC Lung Cancer Working Party.

We conducted a randomized trial testing etoposide (120 mg/m2 d1-3) + vindesine (3 mg/m2 d1) with or without cisplatin (60 mg/m2 d1) in patients with SCLC. A total of 8 courses were given at 3-week intervals. 221 patients were registered and 201, 95 in the CEV arm and 106 in the EV arm, were eligible for survival analysis. 183 patients were evaluable for response: 74% had an objective response (OR) with CEV versus 55% with EV (p = 0.01). Complete response rates were, respectively, 21% and 13% (NS). In patients with limited disease (LD), OR rates were 72% and 61% (NS), and 76% and 48% in extensive disease (ED) (p = 0.01). There was no statistically significant difference in survival between the two regimens (p = 0.745, log rank test). Median survival for EV and CEV were, respectively, 40 and 45 weeks, and two-year survivals were 11% and 9%; in patients with LD, the corresponding figures were 14% and 16% (NS) and in those with ED, 8% and 3% (NS). Disease extent (LD vs ED), Karnofsky performance status and loss of body weight were significant prognostic factors for survival; age, sex, type of treatment and type of lesion were not. The CEV regimen was not significantly more myelotoxic than EV but was associated with more severe nausea, vomiting and alopecia. In conclusion, the addition of cisplatin to the EV regimen, a combination reported to be easily manageable, was associated with a significantly higher OR rate but survival was not significantly improved.

Adult↗
PubMed1990

Empiric treatment of infection during granulocytopenia.

Results from clinical trials conducted over the past 15 years suggest the following: a) Early empiric therapy with broad-spectrum antibiotics directed against Gram-negative bacillary bacteremia is necessary in febrile granulocytopenic cancer patients; b) The level and dynamics of the granulocyte count are extremely important in determining the outcome of bacteremia; c) Most empiric antimicrobial regimens will require therapeutic modifications; these alterations are necessary and contribute to a high overall success rate; d) Only microbiologically documented infections and especially bacteremias are useful for comparison of initial response to antimicrobial regimens; e) The response rate of Gram-negative bacillary bacteremia is clearly influenced by the susceptibility of the causative pathogen to the beta-lactam component of the empiric regimen; emergence of resistance to some beta-lactam antibiotics is quite common and necessitates successive modifications of empiric regimens with time; f) The combination of an anti-pseudomonal beta-lactam with an aminoglycoside is recommended as the standard for empiric therapy in febrile granulocytopenic cancer patients, especially in those with severe and persistent granulocytopenia who are suspected of having Gram-negative bacillary bacteremia; less neutropenic and/or asymptomatic patients may do well with monotherapy; g) Gram-positive pathogens have become a common cause of bacteremia in granulocytopenic cancer patients; the response rate to empiric regimens may be suboptimal but the associated mortality is low; h) Patients with severe granulocytopenia and protracted fever whose blood cultures remain negative are at high risk for contracting fungal infections; in these patients, empiric antifungal agents are probably indicated.

Agranulocytosis↗
PubMed1990

Chemoprophylaxis of gram-negative infections in neutropenic patients.

Gram-negative infections in neutropenic patients originate frequently from the gut flora. Attempts to decrease the incidence of these infections have utilized several regimens for gastrointestinal decontamination, of which some have proven to be clinically useful. Orally administered nonabsorbable antibiotics (aminoglycosides, polymyxins) can decrease the incidence of gram-negative sepsis during neutropenia, but, with the possible exception of netilmicin, tolerance to these agents is generally poor, and compliance is low. Trimethoprim-sulfamethoxazole has been used widely for the prophylaxis of infections in neutropenic patients. Clinical results with this agent have been conflicting, as its efficacy is clearly related to epidemiological patterns of resistance of the pathogens in the population under study. More recently, the quinolones, which are well tolerated by patients and are presently active on most strains of Enterobacteriaceae, have been associated with a virtual eradication of gram-negative infections in neutropenic patients. These results have been paralleled by an increase in the frequency of gram-positive infections, which, fortunately, cause an incidence of mortality that is much lower than that seen in gram-negative sepsis. The fact that the quinolones are absorbed systemically might help to explain their efficacy in chemoprophylaxis during neutropenia. This paper discusses the chemoprophylaxis of gram-negative infection during neutropenia in the light of theoretical concepts such as 'colonization resistance', 'selective decontamination', and 'bacterial translocation'.

Agranulocytosis↗
PubMed1990

A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861.

The European Organization for Research and Treatment of Cancer (EORTC) Lung Cancer Working Party conducted a randomized trial comparing cisplatin (CDDP; 120 mg/m2, day 1) and carboplatin (CBDCA; 325 mg/m2, day 1) in combination with etoposide (VP16; 100 mg/m2, days 1, 2, and 3) in advanced non-small-cell lung cancer (NSCLC). Two hundred twenty-eight patients were eligible for survival and 202 assessable for response. We obtained 27 of 100 objective responses (ORs; 27%) in the CDDP arm and 16 of 102 (16%) in the CBDCA arm (P = .07). There was no significant difference in survival. Toxicity, consisting mainly of myelosuppression and renal function impairment, was significantly increased in the patients receiving the CDDP treatment. We conclude that CDDP plus VP16 was more active but also more toxic than CBDCA plus VP16 in advanced NSCLC.

Adult↗
PubMed1990

A randomized trial of two platinum combinations in patients with advanced non-small cell lung cancer: a preliminary report. European Organization for the Research and Treatment of Cancer--Lung Cancer Working Party.

A randomized study with cisplatin (120 mg/m2) or carboplatin (325 mg/m2) plus etoposide (100 mg/m2, days 1 to 3) in 162 evaluable patients with advanced non-small cell lung cancer (NSCLC) compared response and survival after treatment. No statistically significant difference in survival rates was detected; median survival was 25 weeks for patients receiving cisplatin and 24 weeks for those receiving carboplatin. The objective response rate was 25% for cisplatin plus etoposide and 20% for carboplatin plus etoposide. Granulocytopenia, diarrhea, and nephrotoxicity were significantly more frequent with cisplatin plus etoposide than with carboplatin plus etoposide. Severe nausea and/or vomiting occurred during 59 of 77 courses (77%) with cisplatin and 48 of 75 (64%) with carboplatin (P = .13). Unlike cisplatin plus etoposide, carboplatin plus etoposide was administered on an outpatient basis. At the dose used in the present study, carboplatin plus etoposide was as effective as but less toxic than cisplatin plus etoposide for NSCLC and could be given more easily.

Adenocarcinoma↗
PubMed1989

[Adoptive immunotherapy with interleukin 2. Initial results of a pilot study in 6 cancer patients].

Adoptive immunotherapy of cancer consists of using interleukin-2 to induce the formation of lymphokine-activated killer (LAK) cells which are toxic to tumoral cells. Six patients, 3 with hypernephroma and 3 with melanoma, were treated with interleukin-2. Drug toxicity consisted of capillary leakage syndrome in one case and reversible renal impairment in another. One patient showed an objective response; transient subjective improvement was observed in all patients.

Acute Kidney Injury↗
PubMed1989

Immunoprophylaxis of cytomegalovirus infections in transplanted patients.

Cytomegalovirus causes severe infections in immunosuppressed patients and anti-viral treatments remain unsatisfactory. In an attempt to prevent life-threatening CMV infections, immunoprophylaxis using hyperimmune immunoglobulins has been studied but led to conflicting results in the literature. The role of passive immunization in allogeneic marrow and renal transplant patients is discussed.

Bone Marrow Transplantation↗
PubMed1989

Tolerance and effectiveness of recombinant interleukin-2 (r-met Hu IL-2 [ala-125]) and lymphokine-activated killer cells in patients with metastatic solid tumors.

The tolerance of a recombinant human interleukin-2 (rIL-2, r-met Hu IL-2 [ala-125], Ortho Pharmaceutical) and its antitumor effectiveness in combination with lymphokineactivated killer (LAK) cells was examined in 26 patients with metastatic solid tumors, including 14 renal cell carcinomas, seven melanomas, three extragonadal germ cell tumors refractory to chemotherapy and two colon carcinomas. rIL-2 was administered as a bolus at 30,000 U/kg every 8 h on days 1-5 and days 12-19. Leukapheresis was done on days 8-12, lymphocytes were incubated with rIL-2 for 3 or 4 days in vitro and reinfused on days 12, 13 and 15. The mean number of reinfused cells was 5.1 x 10(10) per patient. IL-2 dose and schedule were adjusted according to toxicity. Patients received a median of 100% (range 87-100%) of planned rIL-2 on days 1-5 and a median of 71% (range 13-100%) on days 12-19. Capillary leak syndrome with hypotension and impaired renal function and CNS toxicity were the major reasons for dose modification. Patients with renal cell carcinoma, most of whom underwent a prior nephrectomy, had a reduced tolerance to rIL-2. Partial responses were documented in three renal cell carcinomas and one melanoma. The median response duration was 5.5 (range 1-6) months.

Adult↗