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Biomedical subjects

J Klastersky

Publications and source records attributed to J Klastersky.

At least 55 records · Page 3Linked to original sources
PubMed1998

Imipenem versus targeted therapy in cancer patients.

In many instances, broad-spectrum antibiotics are initiated empirically in febrile cancer patients and continued for the whole duration of therapy. An alternative is to narrow the spectrum whenever the offending pathogen is identified. This study is aimed at comparing these two options. Non-neutropenic cancer patients with severe infections received empiric imipenem. After 72 h, those with microbiologically documented infection were randomized either to continue imipenem or to receive a targeted therapy. After 72 h of imipenem 76.1% were improved. After randomization, a higher efficacy was observed with imipenem (88.5 vs. 72.1%: P = 0.025). Bacterial and fungal superinfections were comparable. Costs were lower for targeted therapy in gram-positive infection and higher in gram-negative infection.

Anti-Bacterial Agents↗
PubMed1998

Science and pragmatism in the treatment and prevention of neutropenic infection.

The following aspects of the management of patients with granulocytopenia and fever are reviewed in this article: adaptation of initial antibiotic regimens to the recent changes in the most common causative pathogens (namely a change from Gram-negative bacteria to Gram-positive bacteria and fungi); subsequent modifications of the empirically administered treatments; improvement of the host's defence by reducing the duration of neutropenia; and indications for out patient therapy of febrile episodes.

Anti-Bacterial Agents↗
PubMed1998

Current attitudes for therapy of febrile neutropenia with consideration to cost-effectiveness.

Febrile neutropenia is a changing syndrome which requires periodic updates as our armamentarium against this condition improves, and the characteristics of the pathogens change. In addition, cost of therapy has become a major issue when designing therapeutic strategies. This article reviews the basis of the current therapeutic approaches to febrile neutropenia, and this information is used to propose an algorithm for the management of this condition taking into consideration, in addition to these medical aspects, cost-effectiveness.

Cost-Benefit Analysis↗
PubMed1998

Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE: A phase III randomized trial in patients with advanced non-small-cell lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to moderate-dose cisplatin and carboplatin improved response rate (primary end point) and survival. PATIENTS AND METHODS: A total of 529 patients were randomized to receive a combination of moderate-dose carboplatin (200 mg/m2 intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238 patients assessable for response, respectively. All but 23 had stage IV disease with pleural effusion. RESULTS: There was a 16% objective response (OR) rate to CC and a 31% OR rate to CCI. That observed difference was highly statistically significant (P < 0.001). Duration of response and survival were not statistically different between arms. The CCI regimen was associated with significantly more acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The frequency of chronic renal, auditive, and peripheral neurologic toxicity was low in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy). The relative dose-intensity (RDI) of the CCI arm was significantly lower than that of the CC arm. CONCLUSION: The addition of ifosfamide to moderate-dose cisplatin and carboplatin significantly improves the antitumoral response rate, but has no apparent effect an survival in advanced NSCLC.

Adult↗
PubMed1998

[The infectious complications of bronchial cancer].

Infection are part of the natural course of lung cancer but overall they are poorly understood. The clinical studies on which is based our knowledge often lack sufficient clinical and microbiological documentation of the infection. Nevertheless, infection is frequently caused by Gram+ pathogens, among which pneumococci remain common. When lung cancer patients are treated with chemotherapy, the resulting neutropenia predisposes further to infection; its spectrum is similar to what has been observed in other granulocytopenic patients. The frequency and severity of the infection depends mainly on the severity and duration of neutropenia. Cotrimoxazole prophylaxis in neutropenic patients with lung cancer has been found effective in several studies. As far as therapy of fever and/or infection in neutropenic lung cancer is concerned, it does not appear that it should be handled differently from febrile neutropenia in other chemotherapy treated neutropenic patients.

Anti-Infective Agents↗
PubMed1997

Treatment of neutropenic infection: trends towards monotherapy?

Febrile neutropenia has been a changing syndrome over the last 20 years. The perspectives and goals that we face today are mainly the constant adaptation of antibacterial prophylactic and therapeutic regimens to the emergence of resistant strains; the definition of prognostic factors influencing the outcome of febrile neutropenia; the introduction of pragmatic algorithms for adaptation of therapy; ambulatory and/or home therapy for certain categories of patients; the definition of indications for the use of cytokines to restore earlier bone marrow function and to help with home management of febrile neutropenia, and, finally, the recognition of risk factors for fungal infections and the improvement of our diagnostic as well as therapeutic anti-fungal strategies.

Anti-Bacterial Agents↗
PubMed1997

Response to chemotherapy has predictive value for further survival of patients with advanced non-small cell lung cancer: 10 years experience of the European Lung Cancer Working Party.

The aim of this study was the assessment of the predictive value for survival of an antitumoral response to three courses of chemotherapy in association with various pretreatment characteristics in patients with non-resectable non-small cell lung cancer treated by cisplatin- (or carboplatin)-based combination regimens. Patients considered for this study were eligible patients with advanced non-small cell lung cancer registered in one of the seven trials conducted by the European Lung Cancer Working Party from December 1980 to August 1991. All these trials tested chemotherapy regimens with platinum derivatives (cisplatin and/or carboplatin). In this population of 1052 eligible patients, 752 were assessed in this analysis. Data were prospectively collected on 23 pretherapeutic variables and objective response after three chemotherapy cycles. The predictive value of response to chemotherapy on survival (measured from the time of response assessment i.e. 12 weeks after registration in the trial) was studied by univariate analysis as well as by multivariate methods (adjustment of the impact of several covariates simultaneously on the dependent variable) with adjustment for the pretreatment prognostic variables. After three cycles of chemotherapy, the global estimated median survival time was 24 weeks with a 95% confidence interval of 22-25 weeks. By univariate analysis, we identified an objective response to chemotherapy as a highly significant discriminant marker (P < 0.0001) for further survival with estimated median survival times of 41 weeks (95% CI: 38-46) and 19 weeks (95% CI: 17-20), respectively, for the responding and non-responding patients. In a Cox regression model fitted to the data using a forward stepwise procedure, this variable was the first selected explanatory variable. Its effect was adjusted by the introduction in the model of initial disease extent, Karnofsky performance status, serum calcium level and white blood cell count. These results were consistent with those obtained by application of recursive partitioning and amalgamation algorithms (RECPAM) which led to a classification of the patients into three homogeneous subgroups. Our results, using a classical Cox regression model consistent with those highlighted by application of a RECPAM analysis, found an objective response to chemotherapy to be a predominant predictive factor for further survival, although it did not allow any conclusion about a causal relationship. The RECPAM results led to a classification of the patients into three subgroups which needs to be validated in other series.

Adult↗
PubMed1997

New cytostatic agents for the treatment of head and neck cancer.

Chemotherapy plays a definite role in the management of head and neck cancers, especially in combination with radiotherapy in patients with possibly curable disease. As far as new agents are concerned, the combinations of paclitaxel or docetaxel and gemcitabine with cisplatin or carboplatin deserve special attention. These regimens should be compared to the more classical combinations of cisplatin with Sefluorouracil or Ifosfamide in phase III trials. A special emphasis should be placed on the evaluation of these new agents in combination with radiotherapy, since all have strong radiopotentiating properties.

Antimetabolites, Antineoplastic↗
PubMed1997

[Febrile neutropenia: empiric antibiotic therapy from 1975 to 1997].

Monotherapy with ceftazidime, cefepime, imipenem or meropenem for the empiric treatment of febrile neutropenia appears as effective as the combination therapy involving aminoglycosides. However, empiric therapy with a combination of a beta-lactam plus an aminoglycoside is a reasonable decision under circumstances where Gram negative sepsis is very likely. Monotherapy is usually associated with a modest rate of response in infections caused by Gram positive organisms. In about 30% of the patients, a glycopeptide will be added at some point, because the response to the initial therapy is not considered optimal.

Aminoglycosides↗
PubMed1997

[Gemcitabine: a new chemotherapy agent for solid cancers].

Gemcitabine, a new nucleotide analogue, is a promising chemotherapeutic agent for pancreatic, lung, ovarian and breast carcinomas. Its low toxicity (mainly hematologic) makes it a good choice for palliative treatment in patients who would otherwise be unable to tolerate aggressive therapy. The combination of gemcitabine with other anticancer agents such as cisplatin and anthracyclines appears to be associated with high response rates. Finally, gemcitabine is a potent radiosensitizing agent and should definitely be tested in combination with radiotherapy mainly in locally advanced disease.

Antibiotics, Antineoplastic↗
PubMed1997

[Prognostic factors in advanced stage non-small cell bronchial cancer: experiences of the European Lung Cancer Working Party].

The European Lung Cancer Working Party has investigated prognostic factors for response, overall survival, long term survival in a population with advanced non small cell lung cancer registered in a clinical trial evaluating platinum derivatives-containing chemotherapy regimens. Various factors have been identified in multivariate analyses and were classified using RECPAM methodology. In addition to the clinical factors such as disease extent and performance status were shown, as significant predictors, rarely studied biological factors like pretherapeutic leucocyte and polynuclear levels. The obtention of an objective response to chemotherapy appeared to be a major prognostic factor for further survival.

Age Factors↗
PubMed1997

[Supportive care in oncology].

At the present time, cancer can be cured in about 50% of the patients, mainly through surgical procedures associated or not with radiotherapy and/or chemotherapy. For the rest of these patients, therapy will only be palliative; in other words, these patients will not be cured but radiation therapy and/or chemotherapy will control the symptoms of the neoplastic disease and improve the survival in a substantial proportion of them. In those patients, it is essential to weight the benefits and the risks of such palliative therapies in order to maintain an optimal quality of life. Supportive care is aiming at the control of all the manifestations associated with specific treatment of cancer. The nature of supportive care changes as the neoplastic disease progresses; eventually, it will consist only of measures providing optimal comfort to the patients.

Female↗
PubMed1996

Initial empirical antibiotic therapy for neutropenic fever: analysis of the causes of death.

We have reviewed the records of all patients who were included in EORTC-IATCG protocols for the empirical treatment of febrile neutropenia at the Institut Jules Bordet from 1984 to 1994. Of the 410 granulocytopenic patients, 49 died during or after febrile neutropenia. Among these, 19 died from infection, 18 from progressive neoplasia, and 12 from other causes. Fatal bacterial infection occurred in 10 patients and arose during the first 10 days; fatal fungal infection occurred in 7 patients, all of whom had a profound and protracted granulocytopenia (polymorphoneutrophil count < 100/mm3 for more than 20 days). In comparison with a previous similar study (1974-1983) our present observations shows a decrease of overall mortality during or after febrile neutropenia and an increase of gram-positive microorganisms and fungal pathogens as a cause for infectious deaths.

Agranulocytosis↗
PubMed1996

Prognostic factors for response to chemotherapy containing platinum derivatives in patients with unresectable non-small cell lung cancer. (NSCLC).

PURPOSE: To identify pretreatment variables predicting response to platinum derivatives containing chemotherapy in patients with unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients included in one of the 7 consecutive clinical trials conducted by the European Lung Cancer Working Party between December 1980 and August 1991. All patients received a cisplatin or carboplatin containing chemotherapy. We analyzed 22 potential prognostic factors including sex, age, histology, performance status, weight loss, type of lesions, extent of disease, main metastatic sites and several biological parameters, namely white blood cell count (WBC), neutrophil count, platelet count, hemoglobinemia, creatininemia, serum alkaline phosphatases and LDH. RESULTS: On 1052 eligible patients. 107 were not assessable for response. The objective response rate was 26% (95% C.I.: 23, 29%). Univariate analysis identified as statistically significantly associated with a higher objective antitumoral response rate the following characteristics: a normal platelet count, the absence of skin metastasis, the absence of adrenal metastasis, a higher creatininemia, a normal hemoglobinemia, an older age and a normal WBC count. On a restricted set of variables including data from 777 patients, a multivariate logistic regression model disclosed age and platelet count as significantly and independently related to response rate. CONCLUSION: Clinical and demographic characteristics of patients with unresectable NSCLC, as well as routine laboratory parameters, could not accurately predict response to chemotherapy in a population of patients selected for a clinical trial. Future studies on this subject should include more sophisticated variables as new biomolecular makers.

Adult↗
PubMed1996

Prevention of infection in neutropenic cancer patients.

The prophylactic or pre-emptive approach should help to restrict use of antibiotics and lead to better management of infection. It is clear that if effective pre-emptive therapy is available (be it as prophylaxis), the empiric additions of other agents should be taken into account and tailored accordingly. On the other hand, prophylaxis carries the risk of resistance emergence, and subsequent microbiological investigations and empiric therapy should be selected taking that risk into account. We definitely need more studies integrating both pre-emptive therapy (also called prophylaxis) and empiric therapy for febrile episodes. Both interventions are to be seen as a continuous action rather than as two consecutive steps in the approach of the neutropenic patient. Finally, all neutropenic patients are not identical, and thus, they do not require identical approaches. It might well be that prophylaxis is needed only in some subsets of the neutropenic population and not in others.

4-Quinolones↗
PubMed1996

Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Infection Program.

Combinations of beta-lactams plus aminoglycosides have been standard therapy for suspected infections in granulocytopenic cancer patients, especially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended-spectrum cephalosporins or carbapenems, the need to combine beta-lactams with aminoglycosides became more controversial. The objective of this prospective randomized multicenter study was to compare the efficacy, safety, and tolerance of meropenem monotherapy with those of the combination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patients, 958 were assessable in the intent-to-treat analysis for response to antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutropenia were 16 and 17 days, respectively. A successful outcome was reported in 270 of 483 (56%) patients treated with monotherapy compared with 245 of 475 (52%) patients treated with the combination group (P = 0.20). The success rates in the monotherapy group and the combination group were similar by type of infection (single gram-negative bacteremia, single gram-positive bacteremia, clinically documented infection, and possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not differ between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patients treated with the monotherapy compared with 13 patients treated with the combination). A total of 1,027 patients were evaluable for adverse events; the proportion of those who developed adverse effects was similar between the two groups (29% in both groups), and only 19 (4%) patients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protocol antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persistently granulocytopenic cancer patients, and both regimens were well tolerated.

Adolescent↗