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Biomedical subjects

J Klastersky

Publications and source records attributed to J Klastersky.

At least 91 records · Page 5Linked to original sources

Factors associated with bacteraemia in febrile, granulocytopenic cancer patients. The International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC).

The objective of this investigation was to determine factors predictive of bacteraemia at presentation in febrile, granulocytopenic cancer patients in order to estimate the probability of bacteraemia in each patient, and to compare factors associated with a diagnosis of gram-positive or gram-negative bacteraemia. Retrospective analysis of two sets of data (derivation and validation sets) randomly obtained from a large prospective study was conducted in a multicentre study of febrile, granulocytopenic cancer patients admitted for empiric antibacterial therapy. Within the derivation set, prognostic factors (clinical and laboratory data) likely to be associated with a generic diagnosis of bacteraemia and with a specific diagnosis of gram-positive or gram-negative bacteraemia were analysed by means of three backward, stepwise, logistic regression analyses. The predictive probability of bacteraemia was calculated using the logistic equation. The discriminating ability of the model in predicting bacteraemia was evaluated in the derivation and validation sets using receiver-operating characteristic curves. The predictive probability of gram-positive or gram-negative bacteraemia was not calculated. In the derivation set, 157 of 558 episodes (28%) were microbiologically documented bacteraemias. Predicting factors were antifungal prophylaxis, duration of granulocytopenia before fever, platelet count, highest fever, shock and presence and location of initial signs of infection. The variables institution, antibacterial prophylaxis and underlying disease showed borderline associations with bacteraemia. Shock was associated with gram-negative bacteraemia, while signs of infection at catheter site were predictive of gram-positive bacteraemia. Quinolone prophylaxis was negatively associated with gram-negative bacteraemia. When tested in the validation set, the model was poorly predictive, although a small subgroup of episodes (representing only 16% of the total sample size) with low risk of bacteraemia was identified. Factors predictive of bacteraemia can be identified, with discrimination between gram-positive and gram-negative aetiology. Further studies are warranted in order to improve the discriminant ability of the model.

Adolescent↗

A four-drug combination chemotherapy with cisplatin, mitomycin, vindesine and 5-fluorouracil. A regimen associated with major toxicity in patients with advanced non-small lung cancer. European Lung Cancer Working Party.

PURPOSE: To determine in patients with advanced non-small cell lung cancer the activity of a 4-drug combination chemotherapy. PATIENTS AND METHODS: Chemotherapy consisted of the administration of cisplatin (30 mg/m2 d 1-3 or 4), mitomycin C (10 mg/m2 d 1), vindesine (3 mg/m2 d 1) and 5-FU (1 g/m2 d 1-3 or 4 by continuous intravenous infusion. RESULTS: 182 were eligible patients. A 34% objective response rate was observed in the 164 evaluable patients. The overall median survival was 26 weeks. The most serious adverse event was the occurrence of 18 (10%) cardiac or sudden deaths. These toxic deaths were significantly associated with a > or = 5% loss of body weight prior to therapy. CONCLUSIONS: The regimen studied resulted in a very significant cardiac toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Supportive care.

For cancer patients, quality of life and satisfaction with care are not only related to patient treatment facilities, but also to ambulatory care. Therefore, the goal of ambulatory care should be to prevent predictable morbidities, to eliminate residual morbidities when possible, to control symptoms, and to lessen discomfort when cure is not likely. Truly multidisciplinary services should be available and assessed for their effectiveness, the aim being to respond optimally to patients' needs, whether or not these needs are related to the disease or treatment. Research in this area is urgently needed.

Ambulatory Care↗

Phase II randomized trial comparing high-dose cisplatin with moderate-dose cisplatin and carboplatin in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE: A phase II randomized trial was conducted in patients with advanced non-small-cell lung cancer (NSCLC) to determine if the combination of moderate-dose cisplatin and carboplatin was active (primary end point) and could avoid the long-term limiting (renal, auditive, neurologic) toxicity of high-dose cisplatin, which prevents prolonged administration (secondary end point). PATIENTS AND METHODS: One hundred twenty-one patients, registered between April 1990 and September 1991, were randomized to receive high-dose cisplatin (120 mg/m2 intravenously [IV] on day 1) or a combination of moderate-dose carboplatin (200 mg/m2 IV on day 1 and moderate-dose cisplatin (30 mg/m2 IV on days 2 and 3). One hundred nine patients were eligible: 56 in the cisplatin arm and 53 in the combined arm; 52 and 47, respectively, were assessable for response. All had stage IV disease (or stage IIIB with pleural effusion) and none had received prior chemotherapy. RESULTS: There was a 23% objective response rate to cisplatin (23% of the eligible patients) and a 22% response rate to cisplatin plus carboplatin (21% of the eligible patients). The overall survival rate was not significantly different between the two study arms, but responders in the combined arm survived significantly longer than those in the high-dose cisplatin arm (respective median survival durations, 66 and 30 weeks). Although there was no difference between the arms for alopecia, emesis, and leukopenia, the combined arm was significantly associated with more thrombocytopenia (although rarely severe) and, more importantly, with less renal (19% v 36%), auditive (4% v 16%), and neurologic (0% v 16%) toxicity of any grade. CONCLUSION: The regimen combining moderate-dose cisplatin and carboplatin was active against advanced NSCLC and significantly less toxic than high-dose cisplatin.

Actuarial Analysis↗

Dose-finding study of paclitaxel (Taxol) plus cisplatin in patients with non-small cell lung cancer.

We present preliminary results of a study undertaken in previously untreated patients with non-small cell lung cancer to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when administered as a 3-hour intravenous infusion in combination with cisplatin every 3 weeks; to evaluate the nature, frequency, severity, and duration of adverse events associated with this drug combination; and to evaluate the combination's antitumor efficacy. Thus far, we have treated 10 patients with cisplatin (100 mg/m2) and increasing doses of paclitaxel (135, 170, and 200 mg/m2). Among nine evaluable patients, four partial responses have been obtained, disease in three patients progressed after three courses, and no changes were seen in one patient. One patient had two cardiac arrests within 8 days of the onset of therapy, from which he recovered; he died 1 month later of massive hemoptysis. Thrombocytopenia was not seen in these patients, and neutropenia (< 1,000 granulocytes/microL) was seen in only three patients. Infections were seen in these patients and were manageable in all cases. Other toxicities consisted mainly of World Health Organization grades II and III alopecia and nausea and/or vomiting. No grade III nephrotoxicity, neurotoxicity, hypersensitivity, mucositis, or infection was seen in this series after one to three courses of chemotherapy; one patient presented with grade IV cardiotoxicity 6 days after the onset of therapy. So far, the maximum tolerated dose of the cisplatin/paclitaxel combination has not been reached; however, definitive conclusions await the full treatment of additional patients. Moreover, the possibility of cumulative and delayed toxicity must be evaluated after a sufficient duration of follow-up in adequate numbers of patients.

Adolescent↗

Febrile neutropenia.

Fever is associated with malignancy and is a common problem in cancer patients. Fever in the cancer patients is closely linked with infection, especially when the patient is granulocytopenic. When fever appears, a series of diagnostic and therapeutic measures must be taken even if precise knowledge of the cause of the infection is lacking. Fever can be caused by infection or by the cancer itself through tumor-related necrosis, hemorrhage or pyrogens. Infection is the more common cause, however. Bacterial and fungal sepsis can coexist and the bacteremia can overshadow the more difficult to determine fungal infection. For this reason it has become accepted practice to administer amphotericin B to granulocytopenic patients who remain febrile after a few days of broad-spectrum antimicrobial therapy and in whom no bacteria can be documented. Viral infection is rarely diagnosed in neutropenic patients without concomitant immunosuppression.

Amikacin↗

Febrile neutropenia.

Severe neutropenia and its related infectious complications remain a permanent threat for patients receiving intensive chemotherapy, especially in the context of bone marrow transplantation. Chemoprophylaxis and use of colony-stimulating factors have altered the severity of the clinical picture in a favorable direction: neutropenia can be shortened, and gram-negative infection can be made less frequent; neither can be yet abolished. Early therapy, eg, empiric combination treatment, remains the cornerstone of our approach to febrile neutropenia; the actual choice of agents is probably less important and should be guided by local epidemiologic conditions. The concepts of empiric therapy also starts to be more widely accepted for the control of fungal and viral infections. Finally, it is fair to recognize that, at the other end of the spectrum of febrile neutropenia, conventional chemotherapy that results in only moderate and short neutropenia can usually be managed without much problem, namely with broad-spectrum monotherapy. Other possible simplified approaches should be investigated under controlled conditions and in patients selected on the basis of favorable prognostic factors.

Antineoplastic Agents↗

[Should inoperable pulmonary cancer be treated?].

Our review analyses the rationale for chemotherapy in inoperable non small cell lung cancer. We concluded that such a treatment might be beneficial in about 30% of the patients. It is however a potentially toxic approach; the inconveniences can be reduced by a close follow-up and the use of various techniques of supportive care.

Antineoplastic Combined Chemotherapy Protocols↗

Streptococcal and enterococcal bacteremia in patients with cancer.

Eighty-two episodes of bacteremia due to streptococci (including the genus Enterococcus) in 78 patients hospitalized at Institut Jules Bordet between 1986 and 1988 were reviewed. The incidence ranged from 5.5 to 7.6 per 1,000 admissions (16% of all bacteremias). Enterococcus faecalis, Streptococcus sanguis, and Streptococcus mitis were the most prevalent isolates, followed by Streptococcus angionosus, Streptococcus salivarius, and large colony-forming beta-hemolytic species (A, B, C, and G). Twenty-one episodes were polymicrobial. One-half of the patients had solid tumors, and one-half had hematologic malignancies. Forty-two patients were neutropenic (less than 1,000 polymorphonuclear neutrophils/microL). Only 15 episodes were acquired outside the hospital, and 11 episodes were breakthrough bacteremias. Twenty patients died within 1 month of the onset of streptococcal bacteremia. Five patients, two of whom were neutropenic, had fatal adult respiratory distress syndrome. The source of bacteremia remained undetermined in 35.4% of the episodes; the oral mucous membrane and the gastrointestinal tract were the most frequently recognized associated sites of infection. No unexpected antimicrobial resistance was observed except in two penicillin-resistant strains, one S. mitis and one E. faecium. No relation between peak or trough serum bactericidal titers and outcome could be demonstrated.

Adult↗

Monoclonal immunoradiometric assay and polyclonal radioimmunoassay compared for measuring neuron-specific enolase in patients with lung cancer.

Neuron-specific enolase (NSE) is the most sensitive and specific tumor marker for small-cell lung cancer (SCLC). We evaluated a new monoclonal IRMA (Sangtec) for NSE and compared it with a polyclonal RIA (Pharmacia) in patients with SCLC or other lung cancers (NSCLC). We measured NSE concentrations in 100 healthy subjects (NI group), 100 patients with benign pulmonary diseases (BPD group), and 194 patients with advanced lung cancer (97 SCLC and 97 NSCLC). Intra- and interassay CVs were less than 7% for both assays, and dose-dilution curves paralleled their respective standard curves. Values measured by both assays were highly correlated in all groups. NSE concentrations were significantly (P less than 0.001) lower by IRMA than by RIA in NI and BPD groups. The upper 95th percentile values for NSE in the NI group were 11.7 micrograms/L in the RIA and 9.2 micrograms/L in the IRMA. In NSCLC, the values were significantly (P less than 0.05) lower by IRMA but the percentage of subjects with increased values was higher (vs the NI group, 31% for RIA and 44% for IRMA, P less than 0.005). Diagnostic sensitivity for SCLC was improved with IRMA: 83% of values with RIA and 93% with IRMA were increased above the NI group values (P less than 0.005); the corresponding values for SCLC vs BPD were 81% and 89% (P less than 0.05). NSE values measured in 39 patients with SCLC after chemotherapy were more often increased and were significantly higher with the IRMA than with the RIA (P less than 0.005).

Adolescent↗

[Small-cell lung cancer: survival analysis over the last 10 years: 1980-1990].

A review of 269 papers published between 1980 and 1990 has been performed in order to evaluate the median survival (MS) of patients with small cell lung cancer (SCLC) in relationship with different therapeutic modalities. We found that therapies with cisplatin and etoposide were associated with a significantly longer MS than those without these drugs. Alternating regimens, short therapies (< or = 6 months) and maintenance treatments have a similar MS. Initial and late intensification does not significantly prolong the MS as compared to conventional treatments. Neither radiation therapy to the chest and/or to the brain does increase the MS. Overall, MS of patients with limited SCLC is significantly longer than that of patients with extensive disease.

Antineoplastic Combined Chemotherapy Protocols↗

Efficacy of amphotericin B encapsulated in liposomes (AmBisome) in the treatment of invasive fungal infections in immunocompromised patients.

One hundred and twenty-six patients were treated for 137 episodes of fungal infection with liposomal amphotericin B (AmBisome) at 43 investigational centres. Among the patients were 72 with malignancies, 17 organ transplant recipients, 20 patients with immunological disorders and 17 others. AmBisome treatment was instituted after toxicity from previous amphotericin B treatment in 49 cases, nephrotoxicity or renal insufficiency in 40 and failure of previous antifungal treatment in 41. One hundred and eight episodes were clinically evaluable; among these 52 were caused by Candida spp. and 34 by Aspergillus spp. Ninety-nine patients were treated for at least eight days with a maximum dose of 0.7-5 mg/kg/day. Among 64 cases with proven invasive fungal infection 58% were cured. Fungi were eradicated in 35 of 54 (65%) mycologically evaluable cases. The cumulative dose was 3.2 +/- 3.2 (mean +/- S.D.) in cases where fungi were eradicated in comparison with 3.3 +/- 2.3 g in cases where fungi persisted. The eradication rate was 83% for Candida spp. compared with 41% for Aspergillus spp. (P less than 0.01). Among 24 cases with presumptive invasive fungal infections 14 (58%) were cured. Candida spp. were eradicated in seven of ten of these cases. Among 11 cases with superficial fungal infections eight were cured and three improved. Candida spp. were eradicated in four of five patients. It is concluded that AmBisome is an effective antifungal agent in a majority of patients with invasive or superficial fungal infections.

Adolescent↗