Gemcitabine and carboplatin treatment in patients with relapsing ovarian cancer.

Despite progress in primary treatment of patients with advanced ovarian cancer, the majority develop recurrence of the disease. A platinum salt treatment, either as monotherapy or in combination with another cytostatic agent, is indicated for patients who have relapsed 6 or more months after primary treatment and thus have platinum-sensitive relapse. Because repeated use of paclitaxel treatment may lead to substantial neurotoxicity, the combination of gemcitabine with carboplatin represents a suitable treatment option, which is widely used in common clinical practice in the Czech Republic and Slovakia. This non-interventional, prospective study observed the effectiveness and tolerability of second-line treatment with gemcitabine and carboplatin in patients with platinum-sensitive relapse of ovarian cancer in routine clinical practice. The primary endpoint was to evaluate the survival and secondary endpoints were to evaluate time to disease progression, objective tumor response rate, and treatment toxicity. Patients were enrolled to planned second-line treatment with gemcitabine and carboplatin (gemcitabine 1000 mg/m2 and carboplatin AUC 5 on Day 1, and gemcitabine 1000 mg/m2 on Day 8 of a 21-day cycle) for platinum-sensitive relapse of ovarian cancer as a part of routine clinical practice and followed for 12 months. The events (death, tumor progression), tumor response, and maximal grades of toxicity were recorded according to common clinical practice. Survival time (using Kaplan-Meier analysis) and objective tumor response rate were calculated using data forms, and a subgroup analysis was performed using log rank tests for time-to-event endpoints; p-values were also calculated. Response rates were calculated for the whole population; for the subgroups, the Fisher's exact test was performed and only p-values were calculated. Between January 2004 and June 2005, 53 patients were enrolled in the study. The median age was 57 years and 96% of patients had an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0 and 1 at baseline. Approximately 91% of patients were originally diagnosed with stage III or IV; 60% of patients had disease free intervals (DFIs) of 12 or more months from previous therapy, and the additional 40% less than 12 months. The 1-year survival rate was 83%. Median survival time was not determined within the 12-month period following the start of the treatment study due to the limited duration of follow-up. Objective tumour response rate was 67.3%. Most common reasons for discontinuation of therapy were "Planned treatment completed" (53%) and "Tumor progression" (11%). Most common toxicities were leukopenia, anaemia, neutropenia, and thrombocytopenia; grades 3 and 4 of these toxicity types did not exceed 30%. Febrile neutropenia was recorded in two patients. Most common non-haematological toxicities were nausea and vomiting, fatigue, and neuropathy; grades 3 and 4 of these were below 6%. Results on time to disease progression are not published due to inconsistent statistical analysis of reported data. Based on this observation from routine clinical practice, which corresponds with previously published results from controlled clinical trials, the gemcitabine and carboplatin combination seems to be a suitable therapeutic option for patients with platinum-sensitive relapse of ovarian cancer.

[Neo-adjuvant chemotherapy followed by interval debulking surgery in advanced ovarian cancer treatment--a retrospective study]. / Neo-adjuvantná chemoterapia s následnou IDS (interval debulking surgery) v liecbe pokrocilého karcinómu ovária--retrospektívna analýza.

BACKGROUNDS: Primary debulking surgery and chemotherapy (paclitaxel and carboplatin) remain the standard treatment for advanced ovarian cancer. The size of the residual tumour after primary debulking surgery has proved to be an important prognostic determinant. Complete tumour debulking without any macroscopic residual disease is considered the optimal primary debulking surgery. It is not possible to perform such an aggressive operation in patients with advanced ovarian cancer due to the bad performance status and extensive disease. Neo-adjuvant chemotherapy and interval debulking surgery seem to be an effective treatment strategy in this group of patients. MATERIAL AND METHODS: The retrospective analysis evaluated the efficiency of interval debulking surgery in correlation with progression-free and overall survival in patients with advanced ovarian cancer. 38 patients were treated with standard chemotherapy: paclitaxel 175 mg/m2 and carboplatin 5-6 AUC every three weeks. According to the clinical response, surgical debulking was considered, after which postoperative chemotherapy was given. Ineligible patients for interval debulking were treated with 2nd line chemotherapy. RESULTS: After neo-adjuvant chemotherapy, 24 patients of the group of 38 achieved partial remission and interval debulking surgery was indicated. Optimal interval debulking surgery was performed in 12 patients, suboptimal debulking surgery in 12 patients. Of the entire group, 14 patients did not show any adequate response to the primary treatment, they did not have interval debulking surgery indicated and they were treated with 2nd line chemotherapy. Progression-free survival in patients after optimal debulking was 11 months, median overall survival was not achieved (OS > 42.5 months). Progression-free survival in patients after suboptimal debulking was 6 months and median overall survival was 33 months. Median overall survival in patients without surgical treatment was 21.5 months. CONCLUSION: The results of the study confirm that neo-adjuvant chemotherapy with subsequent interval debulking surgery is a suitable therapeutic approach in primary inoperable patients with advanced ovarian cancer.

Analysis of 553 episodes of monomicrobial bacteraemia in cancer patients: any association between risk factors and outcome to particular pathogen?

Relationships between aetiology, various risk factors (such as neutropenia, catheter insertion, endoscopy, therapy with corticosteroids, therapeutic use of antimicrobials, antibiotic prophylaxis, source of infection), symptomatology and outcome were studied in 553 monomicrobial bacteraemic episodes in cancer patients observed within 7 years at the National Cancer Institute of the Slovak Republic. The ratio of gram-positive to gram-negative bacteraemia was 1:1 (43.5% vs 43.8%), and yeasts caused 7.2% of monomicrobial episodes. The highest mortality was associated with Pseudomonas aeruginosa (19.2%), non-albicans Candida yeasts (25%) and Bacteroides fragilis (22.6%). Independent risk factors for particular pathogens were investigated by a computerized logistic regression model. The only independent risk factor for staphylococcal and enterococcal bacteraemia was vascular catheter insertion (OR = 1.95 and 2.05, CI = 95%, P = 0.035 and 0.044, respectively). However, there were no independent specific risk significant factors for viridans streptococcal bacteraemia and bacteraemia due to Enterobacteriaceae or Ps. aeruginosa. Neutropenia was found to be an independent predictor for development of Acinetobacter spp. bacteraemia (OR = 3.84, CI = 95%, P = 0.044). Prior therapy with third-generation cephalosporines was a predictive, independent risk factor for the development of fungaemia (OR = 1.99, CI = 95%, P = 0.028) but not of enterococcal bacteraemia. We also did not observe any association between prior therapy with imipenem and Stenotrophomonas maltophilia bacteraemias. Multivariate analysis confirmed that fungaemia may be independently associated with higher mortality than bacteraemia caused by Enterobacteriaceae and staphylococci. However, the mortality of fungaemia was statistically no different from that of Ps. aeruginosa, Stenotrophomonas spp. and viridans streptococci bacteraemias.

Staphylococcal bacteremia in cancer patients: risk factors and outcome in 134 episodes prior to and after introduction of quinolones into infection prevention in neutropenia.

A total of 134 episodes of staphylococcal bacteremia (SBE) appearing among 9987 admissions, and 979 episodes of bacteremia in cancer patients within 5 years, were analyzed for risk factors, clinical course and outcome; 64 were monomicrobial and 70 polymicrobial. The most frequent risk factors were acute leukemia, catheter insertion, long-lasting neutropenia, and prior prophylaxis with quinolones. There was no significant difference between polymicrobial and monomicrobial SBE in risk factors. The two groups differed only in the source of bacteremia (gastrointestinal and respiratory-tract infections were more common in monomicrobial SBE) and etiology-Staphylococcus aureus appeared more frequently in monomicrobial than in polymicrobial bacteremia (20.3% compared to 4.3%, P < 0.05). More complications (14.3%) such as abscesses, endocarditis, etc. appeared in the group of polymicrobial SBE (P < 0.05). No difference was observed in clinical course and outcome between monomicrobial and polymicrobial SBE. The incidence of SBE has increased since 1991, when quinolones were first used in prophylaxis in afebrile neutropenia at our center; however, the infection-associated mortality in monomicrobial SBE was low (4.3%).

Bacteremia and fungemia occurring during antimicrobial prophylaxis with ofloxacin in cancer patients: risk factors, etiology and outcome.

The authors analyzed 27 breakthrough bacteremias occurring during ofloxacin prophylaxis in afebrile neutropenia over 7 years in 9989 admissions and 979 bacteremic and fungemic episodes in a National Cancer Center in Bratislava, Slovak Republic. The most frequently isolated organisms in breakthrough bacteremias were gram-positive (71.3%), mainly coagulase-negative staphylococci (41.3%), enterococci (9.2%) and Corynebacteria (9.2%), followed by gram-negative rods-Pseudomonas aeruginosa (13.2%) and Stenotrophomonas maltophilia (9.2%). The outcome of breakthrough bacteremias during ofloxacin prophylaxis was not associated with the underlying disease, neutropenia, catheter insertion or resistance, but only with multiple risk factors. A higher failure rate was observed in those patients having a catheter infected with a resistant organism and during neutropenia. No patients with Hickman catheter were included in the study. Patients with mixed breakthrough bacteremia due to gram-negative and gram-positive organisms had higher failure rates than those with monomicrobial bacteremia. Catheter extraction and rapid institution of intravenous antibiotics in combination should be administered in breakthrough bacteremia.

Vancomycin plus imipenem ceftazidime or ciprofloxacin in second line therapy in patients with febrile neutropenia not responding to first line therapy.

137 patients with febrile neutropenia after cytotoxic therapy not responding to ceftazidime plus or ceftriaxone plus netilmicin in received additionally to the previous combination either vancomycin alone or combined with another anti-gram-negative compound: imipenem in those treated prophylactically with ofloxacin and ciprofloxacin in those without prophylaxis. The addition of vancomycin to the previously ineffective combination of a third generation cephalosporin plus aminoglycoside, and replacement of ceftriaxone plus netilmicin with ceftazidime plus amikacin plus vancomycin or with ceftazidime plus vancomycin seems to be less effective (71.8-75 vs. 87.5-90.9%, p < 0.02) and more toxic (20.5-7.2 vs. 0-5%, p < 0.0005) than vancomycin in combination with a different anti-gram-negative compound as previously used: imipenem or ciprofloxacin.

Bloodstream infections due to anaerobic bacteria in cancer patients: epidemiology, etiology, risk factors, clinical presentation and outcome of anaerobic bacteremia.

Thirty one bacteremic episodes (BE) in 31 patients due to anaerobic bacteremia (AB) in 979 BE among 9986 admissions at a 360 beds National Cancer Institute within last 6 years were analyzed for time distribution, risk factors, clinical presentation and outcome. Overall incidence of AB was 3.6%, but the proportion to other groups of microorganisms is decreasing. 73% were Bacteroides fragilis, 10.8% Peptostreptococci and Propionibacteria and 5.4% Clostridia. The most common risk factor for AB was prior surgery, solid tumor as underlying disease, prophylaxis with quinolones and previous therapy with third generation cephalosporines. 48.4% of AB were polymicrobial. Infected wound was the most common source of infection in 38.7% of our cancer patients. Six patients (19.4%) presented septic shock, and 45.2% died, but only in 22.6% death was related to bacteremia. Comparing the groups of AB due to B. fragilis (BF) to non-Bacteroides spp. (NB)AB, infection-associated mortality was higher in BFAB in comparison to NBAB. Other risk factors such as hematologic malignancies, previous prophylaxis with quinolones, prior surgery and prior therapy with broad spectrum antimicrobials, were more frequently associated with BFAB.

Amphotericin B lipid complex to treat invasive fungal infections in cancer patients: report of efficacy and safety in 20 patients.

20 patients with proven or suspected fungal infections were treated with the amphotericin B lipid complex (ABLC) with a daily dose of 5 mg/kg for 1-25 days. 6 patients died during the therapy due to fungal infection (3) or underlying disease (3). One patient was not evaluable. 13 patients were cured and improved. ABLC was administered in patients with renal disease avoiding the use of conventional amphotericin B (AmB) because of nephrotoxicity or after failure with AmB. Except for hypokalemia persisting after AmB in 5 patients, no systemic adverse reaction appeared. ABLC is a promising, well-tolerated and effective drug for the therapy of fungal infections after the failure of a previous antifungal therapy or after toxic reactions due to AmB.