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Biomedical subjects

J Klastersky

Publications and source records attributed to J Klastersky.

At least 37 records · Page 2Linked to original sources
PubMed2001

Association between antifungal prophylaxis and rate of documented bacteremia in febrile neutropenic cancer patients.

Published data have suggested a correlation between antifungal prophylaxis and bacteremia in febrile neutropenia. This correlation was investigated among 3002 febrile neutropenic patients enrolled in 4 trials during 1986-1994. Globally, 1322 patients (44%) did not receive antifungal prophylaxis; 835 (28%) received poorly absorbable antifungal agents and 845 (28%) received absorbable antifungal agents. The rates of bacteremia for these groups were 20%, 26%, and 27%, respectively (P=.0001). In a multivariate model without including antifungal prophylaxis, factors associated with bacteremia were: age, duration of hospitalization, duration of neutropenia before enrollment, underlying disease, presence of an intravenous catheter, shock, antibacterial prophylaxis, temperature, and granulocyte count at onset of fever. When antifungal prophylaxis was included, the adjustment quality of the model improved slightly (P=.05), with an odds ratio of 1.19 (95% confidence interval [CI], 0.92-1.55) for patients receiving nonabsorbable and 1.42 (95% CI, 1.07-1.88) for those who were receiving absorbable antifungal agents. Antifungal prophylaxis with absorbable agents might have an impact on the rate of documented bacteremia in febrile neutropenia. This effect should be confirmed prospectively.

Adolescent↗
PubMed2001

Anticancer chemotherapy in a patient with prior history of acute intermittent porphyria. A case report and review of the literature.

We describe the case of a patient with a prior history of acute intermittent porphyria (AIP) who needed the administration of anticancer drugs. Our experience with this patient and the limited experience reported in the literature show that it is probably safe to administer some chemotherapeutic agents, but it is important to prevent (or to minimize) the toxicities of these chemotherapeutic agents, as they seem to put the patient at major risk of an AIP crisis. Hematin and supportive treatments were useful treatments in our patient.

Aged↗
PubMed2001

Response to chemotherapy, quality of life benefits and survival in advanced non-small cell lung cancer: review of literature results.

The survival benefit obtained with chemotherapy administration in advanced non-small cell lung cancer (NSCLC) patients has been demonstrated by numerous meta-analyses published between 1993 and 1999 on randomised trials comparing best supportive care with or without chemotherapy. However, some clinicians are still reluctant to prescribe chemotherapy in these patients, arguing that the benefit is too small to counterbalance the side effects. The goal of this paper is to review the reasons favouring the administration of chemotherapy. First, there is a demonstrated relationship between response to chemotherapy and survival, although more data are needed to assess response to chemotherapy as a surrogate for survival. Secondly, recent randomised trials comparing best supportive care to chemotherapy, but not included in the meta-analyses, have successfully incorporated quality of life (QoL) as an endpoint, sometimes as a primary endpoint. The survival benefit shown by the meta-analyses is confirmed by these latter trials; in addition, the QoL assessments, despite some methodological problems inherent to attrition in these poor prognosis patients, also favour chemotherapy with regard to some global aspects, such as physical, functioning, emotional, cognitive or social components, as well as some lung cancer symptoms. We conclude that there are no longer convincing arguments against chemotherapy administration in patients with advanced NSCLC, at least in patients eligible for inclusion in clinical trials.

Antineoplastic Agents↗
PubMed2001

Empirical treatment of sepsis in neutropenic patients.

Mortality associated with febrile neutropenia has dramatically decreased over the last three decades; a pivotal role has been played by the concept of hospital-based empirical therapy with broad-spectrum combinations of antibiotics. Nevertheless, there is evidence that a subgroup of patients with febrile neutropenia might benefit from less aggressive treatments.

Ambulatory Care↗
PubMed2001

[Respiratory infections during chemotherapy-induced aplasia].

Damage to local and systemic host defenses of the lung makes the immunocompromised patient vulnerable to inhaled microorganisms. When a pulmonary infiltrate occurs, the array of possibilities is very large including conventional and opportunistic agents. The type of underlying disease and its associated immunodeficiency allow a high degree of accurate pathogen prediction. Neutropenia is associated with Gram-negative bacilli pneumonia. Prolonged neutropenia increases the risk of invasive aspergillosis and other unusual mycotic agents. Cellular immunodeficiency is associated with intracellular microorganisms including Mycobacteria spp., Nocardia spp., Legionella spp., Rhodococcus equi, cytomegalovirus, Strongyloides stercoralis, Toxoplasma gondii, Histoplasma capsulatum, Coccidioides spp., Cryptococcus neoformans and Pneumocystis carinii, parasites such as Toxoplasma gondii and Strongyloides stercoralis, and virus such as cytomegalovirus, Herpes simplex or zoster, adenovirus, respiratory syncitial virus and measles. Humoral immunodeficiency predisposes to infection with encapsulated pathogens such as S. pneumoniae and Haemophilus influenzae. Chest computerized tomography scan and bronchoalveolar lavage are essential procedures for diagnosis. However, despite continuous progress in diagnostic methods, the specific etiology remains often unknown. Successful treatment depends on the type of pathogen, status of host defences and early adequate choice of antibiotic. Enhancement of host defences with growth factors and cytokines may decrease the incidence and improve the final outcome of respiratory infections in the immunocompromised host.

Anti-Bacterial Agents↗
PubMed2000

Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years.

BACKGROUND: The purposes of this study were to identify prognostic factors for response to chemotherapy, overall survival, and long term survival of patients with small cell lung carcinoma and to construct a classification of patients on the basis of their expected overall survival. METHODS: In the 763 patients registered in 4 consecutive clinical trials conducted by the European Lung Cancer Working Party from 1982 to 1993, the impact of 21 pretreatment variables assessable in a routine practice was analyzed for the various outcomes with a minimum follow-up of 5 years. RESULTS: The key prognostic role of disease extent was confirmed for all the outcomes. Additional independent prognostic factors for response to chemotherapy were gender, neutrophil count, and hemoglobin level; for overall survival, these factors were Karnofsky performance status, gender, and neutrophil count. Recursive partitioning and amalgamation algorithms (RECPAM) analysis classified patients into 4 groups, taking into consideration disease extent, Karnofsky performance status, age, gender, and neutrophil count. Median survival times for the 4 groups were 60, 47, 36, and 28 weeks, respectively. For long term survival, defined as a minimum survival of 2 years (9% of the patients), Karnofsky performance status was the only independent predictive factor, along with the achievement of a complete response (if this was taken into consideration). Small cell lung carcinoma remained the main cause of death among these patients. Cure was infrequent, with only 14 patients alive and disease free at 5 years (1.8%). CONCLUSIONS: In this study the long term prognosis associated with small cell lung carcinoma was poor. The well-known prognostic values of disease extent and Karnofsky performance status were confirmed, but the authors also identified age and gender (which are more controversial) as independent characteristics, in addition to citing the role of complete response in the attainment of long term survival. The independent role of neutrophils observed by the authors. must be validated by further studies.

Adult↗
PubMed2000

A phase II trial testing gemcitabine as second-line chemotherapy for non small cell lung cancer. The European Lung Cancer Working Party. 101473.1044@compuserve.com.

The purpose of the present trial was to determine the activity of gemcitabine as a second-line chemotherapy for non small cell lung cancer (NSCLC). To be eligible, patients had to have pathologically proven NSCLC that has failed to respond to a first-line chemotherapy with a cisplatin-containing regimen, a Karnofsky performance status greater than 50 and adequate renal, haematological and hepatic functions. After registration, patients were treated by gemcitabine given i.v. at a dose of 1 g/m(2) on days 1, 8, 15 every 4 weeks. Response was assessed after two courses of therapy. Eighty-two patients have been registered, five are ineligible and 65 are assessable for response. Four partial responses were observed (6%). No change was documented in 18 cases (28%). Tolerance was good. A few grade III leucopenia and grade III-IV thrombopenia were observed. We conclude that gemcitabine has a modest activity as second-line chemotherapy for NSCLC. It has the advantage to be well tolerated and may thus be one drug to be proposed to the patients who have disease progression after a first-line chemotherapy and who ask for further treatment.

Adult↗
PubMed2000

Empirical treatment of sepsis in neutropenic patients.

Febrile neutropenia remains a major cause of morbidity in cancer patients receiving chemotherapy. Although the mortality associated with febrile neutropenia has dramatically decreased over the last three decades, the overall death rate during and immediately after an episode of febrile neutropenia can be as high as 10% with half of the patients dying directly as a result of the infection itself. A series of developments has led to this marked reduction in mortality. Among them, a pivotal role has been played by the concept of hospital-based empirical therapy with broad-spectrum combinations of antibiotics, aimed primarily against Gram-negative organisms, namely Pseudomonas aeruginosa

Anti-Bacterial Agents↗
PubMed2000

Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer.

A phase III randomized trial was conducted in patients with metastatic NSCLC, to determine if, in association with mitomycin (6 mg m(-2)) and ifosfamide (3 g m(-2)), the combination of moderate dosages of cisplatin (60 mg m(-2)) and carboplatin (200 mg m(-2)) - CarboMIP regimen - improved survival in comparison with cisplatin (50 mg m(-2)) alone - MIP regimen. A total of 305 patients with no prior chemotherapy were randomized, including 297 patients assessable for survival (147 in the MIP arm and 150 in the CarboMIP arm) and 268 patients assessable for response to chemotherapy. All but eight (with malignant pleural effusion) had stage IV disease. There was a 27% (95% CI, 19-34) objective response (OR) rate to MIP (25% of the eligible patients) and a 33% (95% CI, 24-41) OR rate to CarboMIP (29% of the eligible patients). This difference was not statistically significant (P = 0.34). Duration of response was not significantly different between both arms. There was also no difference (P = 0.67) in survival: median survival times were 28 weeks (95% Cl, 24-32) for MIP and 32 weeks (95% Cl, 26-35) for CarboMIP, with respectively 1-year survival rates of 24% and 23% and 2-year survival rates of 5% and 2%. The main toxicities consisted in emesis, alopecia, leucopenia and thrombocytopenia, that were, except alopecia, significantly more severe in the CarboMIP arm. Our trial failed to demonstrate a significant improvement in response or survival when patients with metastatic NSCLC were treated, in addition to ifosfamide and mitomycin, by combination of moderate dosages of cisplatin and carboplatin instead of moderate dosage of cisplatin alone. The results support the use of a moderate dose (50 mg m(-2)) of cisplatin in combination with ifosfamide and mitomycin for the chemotherapy of this disease.

Adult↗
PubMed2000

The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients.

PURPOSE: Febrile neutropenia remains a potentially life-threatening complication of anticancer chemotherapy, but some patients are at low risk for serious medical complications. The purpose of this study was to develop an internationally validated scoring system to identify these patients. MATERIALS AND METHODS: Febrile neutropenic cancer patients were observed in a prospective multinational study. Independent factors assessable at fever onset, predicting low risk of complications, on a randomly selected derivation set, were assigned integer weights to develop a risk-index score, which was subsequently tested on a validation set. RESULTS: On the derivation set (756 patients), predictive factors were a burden of illness indicating absence of symptoms or mild symptoms (weight, 5; odds ratio [OR], 8.21; 95% confidence interval [CI], 4.15 to 16.38) or moderate symptoms (weight, 3; OR, 3.70; 95% CI, 2.18 to 6.29); absence of hypotension (weight, 5; OR, 7.62; 95% CI, 2.91 to 19.89); absence of chronic obstructive pulmonary disease (weight, 4; OR, 5. 35; 95% CI, 1.86 to 15.46); presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies (weight, 4; OR, 5.07; 95% CI, 1.97 to 12.95); outpatient status (weight, 3; OR, 3.51; 95% CI, 2.02 to 6.04); absence of dehydration (weight, 3; OR, 3.81; 95% CI, 1.89 to 7.73); and age less than 60 years (weight, 2; OR, 2.45; 95% CI, 1.51 to 4.01). On the validation set, a Multinational Association for Supportive Care in Cancer risk-index score >/= 21 identified low-risk patients with a positive predictive value of 91%, specificity of 68%, and sensitivity of 71%. CONCLUSION: The risk index accurately identifies patients at low risk for complications and may be used to select patients for testing therapeutic strategies that may be more convenient or cost-effective.

Anti-Bacterial Agents↗
PubMed1999

A comparison of methods of calculation for estimating carboplatin AUC with a retrospective pharmacokinetic-pharmacodynamic analysis in patients with advanced non-small cell lung cancer. European Lung Cancer Working Party.

We retrospectively analysed the data obtained in a large randomised trial performed in 505 eligible patients with advanced non-small cell lung cancer. Its purpose had been to compare a combination of carboplatin (200 mg/m2) and cisplatin (60 mg/m2) with or without the addition of ifosfamide. The present retrospective analysis assessed two ways of dosing carboplatin: according to body surface area (mg/m2) or to the estimated targeted area under the concentration versus time curve (AUC). Two different methods were used in the latter calculation: the Calvert formula using the Cockroft approximation to evaluate the glomerular filtration rate and the Chatelut equation. There was an excellent linear correlation between them. With the Chatelut method, the calculated administered AUC were lower. Whichever method was used, carboplatin AUC was not significantly associated with antitumour response rate nor patient survival. A statistically significant increase in haematological toxicity, mainly thrombopenia, was observed with an increase in the AUC. This effect was observed whatever AUC variable was considered, i.e. total dosage at course one, total dosage during the first three chemotherapy courses or dose intensity during the first three courses. The effect remained highly significant after adjustment for treatment arm. We conclude that for a moderate carboplatin dose in non-small cell lung cancer, the therapeutic index could be improved if dosage is calculated according to the AUC.

Adult↗
PubMed1999

A randomised phase III trial comparing consolidation treatment with further chemotherapy to chest irradiation in patients with initially unresectable locoregional non-small-cell lung cancer responding to induction chemotherapy. European Lung Cancer Working Party.

PURPOSE: A phase III randomised trial was conducted in patients with non-metastatic unresectable non-small-cell lung cancer in order to compare, in responders to induction chemotherapy, consolidation treatment by further chemotherapy to chest irradiation. PATIENTS AND METHODS: A total of 462 untreated NSCLC patients were eligible for three courses of induction chemotherapy (MIP) consisting of cisplatin (50 mg/m2), ifosfamide (3 g/m2) and mitomycin C (6 mg/m2). It was proposed that objective responders be randomised to either three further courses of MIP or to chest irradiation (60 Gy; 2 Gy per fraction given over six weeks). RESULTS: An objective response rate of 35% was achieved; 115 patients (including 52% with initial stage IIIA and 44% with initial stage IIIB) were randomised to consolidation treatment, 60 of them to further chemotherapy and 55 to chest radiotherapy. There was no significant difference in survival between the two arms, with a respective median and two-year survival of 42 weeks (95% confidence intervals (95% CI: 35-51) and 18% (95% CI: 8-28) for chemotherapy and 54 weeks (95% CI: 43-73) and 22% (95% CI: 11-33) for irradiation. There was also no statistical difference for response duration between the two arms but chest irradiation was associated with a significantly greater duration of local control than chemotherapy (median duration times: 158 vs. 31 weeks, P = 0.0007). CONCLUSIONS: For non-metastatic unresectable NSCLC treated by an induction chemotherapy regimen containing cisplatin and ifosfamide, if an objective response is obtained, consolidation treatments by further chemotherapy or by chest irradiation result in non-statistically different survival distributions, although a better local control duration is observed with radiotherapy.

Adult↗
PubMed1999

Infection in the neutropenic and stem cell transplant patient.

The spectrum of infectious complications in neutropenic patients after stem cell or bone marrow transplant is not very different from that seen in other neutropenic patients, with the possible exception of fungal infections. The prevention and therapy of these infections remain a major challenge. The management of neutropenic patients after stem cell or bone marrow transplant has markedly benefited from the development of new antiviral agents and the use of granulocyte/macrophage colony stimulating factors.

Journal Article↗
PubMed1998

Lung fibrosis induced by paclitaxel.

In a 59-year old man with IIIb non-small-cell lung cancer, a combined treatment with paclitaxel and carboplatin was used for potentiation of radiotherapy. The patient was alive and free of neoplastic disease 14 months after the end of treatment but irreversible lung fibrosis had developed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

The value of lung function measurements for the assessment of chemotherapy in lung cancer patients.

A retrospective analysis of lung function changes in lung cancer patients (NSCLC and SCLC) receiving various chemotherapy regimens, showed--statistically non significant--improvements of some parameters in responders, especially FEV1 and VC (mean increase of 230 and 310 ml after three cycles of chemotherapy), while stable values were observed in non responders. The majority of patients suffered from a decline in diffusing capacity, irrespective of response. Although the specificity and sensitivity of this functional evaluation are too low to allow lung function parameters to replace more conventional staging procedures, improvement in lung function in responders might indicate that chemotherapy can improve quality of life.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Evaluation of the TN sub-staging in patients with initially unresectable stage III non-small cell lung cancer treated by induction chemotherapy. The European Lung Cancer Working Party.

PURPOSE: This study attempted to investigate, in a cohort of patients with clinical stage III initially unresectable non-small cell lung cancer (NSCLC) treated by the same induction chemotherapy regimen, the prognostic value of clinical T and N sub-groupings in order to validate the current International Staging System (ISS). PATIENTS AND METHODS: All the eligible patients with stage III NSCLC (428 patients) registered in a clinical trial were included in the study investigating, after three courses of induction chemotherapy, the role, in responders, of chest irradiation in comparison to further chemotherapy. The chemotherapy regimen consisted of mitomycin C, ifosfamide and cisplatin. RESULTS: Patients with ISS 1986 stage IIIA had a significantly better survival than those with stage IIIB (median survival 47 vs 36 weeks; P = 0.01). A RECPAM analysis showed that patients with T1-T2 N3 and T4 N0-1-2 stage had a more similar prognosis to those with stage IIIA. That result leads to define two new sub-groups: stage IIIlalpha (T3-T4 N0-N1; any T N2; T1-T2 N3) and IIIbeta (T3-T4 N3), with a highly significant difference in survival between them (median survival: 45 vs 29 weeks; P < 0.0001). The superiority of that new classification on the ISS documented in our series of stage III patients for discriminating survival and tumour response has to be confirmed on another series in a multivariate context. CONCLUSION: For unresectable NSCLC treated by induction chemotherapy, stage III sub-classification by moving T4 N0-1 and T1-2 N3 tumours from stage IIIB to stage IIIA appeared to better correlate with prognosis. The usefulness of this new sub-division has to be tested in validation studies.

Adult↗