PubMed Health⌕ Search

Biomedical subjects

G Samonis

Publications and source records attributed to G Samonis.

At least 37 records · Page 2Linked to original sources
PubMed2003

Systemic mycoses in the immunocompromised host: an update in antifungal therapy.

Despite significant advances in the management of immunosuppressed patients, invasive fungal infections remain an important life-threatening complication. In the last decade several new antifungal agents, including compounds in pre-existing classes (new generation of triazoles, polyenes in lipid formulations) and novel classes of antifungals with a unique mechanism of action (echinocandins), have been introduced in clinical practice. Ongoing and future studies will determine their exact role in the management of different mycoses. The acceleration of antifungal drug discovery offers promise for the management of these difficult to treat opportunistic infections.

Amphotericin B↗
PubMed2003

A dose-escalation and pharmacokinetic study of gemcitabine and oxaliplatin in patients with advanced solid tumors.

BACKGROUND: Gemcitabine and oxaliplatin have broad antineoplastic activity and favorable toxicity. We conducted a phase I study to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of the combination in patients with advanced solid tumors. PATIENTS AND METHODS: Sixty-eight patients with advanced stage solid tumors were enrolled. Treatment was first-line for 35% of patients, second-line for 27%, and third-line for 38%. Gemcitabine was administered at escalating doses of 1000-2000 mg/m(2) as a 30-min intravenous (i.v.) infusion on days 1 and 8 and oxaliplatin at 60-130 mg/m(2) as a 4-h i.v. infusion on day 8 every 21 days without growth factor support. RESULTS: The MTD was defined at gemcitabine 1800 mg/m(2) on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 8. Twelve dose levels were evaluated and DLTs occurring during the first cycle consisted of grade 4 neutropenia, grade 3 asthenia or mucositis and grade 1-3 neutropenia or thrombocytopenia resulting in treatment delays. A total of 266 cycles were administered with only one episode of febrile neutropenia and no toxic deaths. Seven (3%) and 26 (10%) cycles were complicated by grade 4 and 3 neutropenia, respectively, three (1%) and 13 (5%) by grade 4 and 3 thrombocytopenia, and eight (3%) by grade 3 anemia. The most common non-hematological toxicity was grade 2/3 asthenia observed in 23% of cycles. Responses were observed in patients with a variety of epithelial neoplasms. The pharmacokinetic study revealed no significant interaction between the two drugs. CONCLUSIONS: The combination of gemcitabine and oxaliplatin has excellent tolerability and promising activity in patients with advanced solid tumors. As the MTD exceeds the recommended single-agent dose for gemcitabine, and a dose-response effect has not been established, we recommend using both drugs at full doses, e.g. gemcitabine 1200-1400 mg/m(2) on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 8 for further phase II studies.

Adult↗
PubMed2003

Effects of doxycycline, metronidazole and their combination on Candida species colonization of the human oropharynx, intestinal lumen and vagina.

The present study reports about the effect of doxycycline and/or metronidazole on colonization by Candida organisms of the human gastrointestinal (GI), oropharyngeal tract and vagina. Treatment with doxycycline or metronidazole for 10 days increased, but not significantly, the GI, oropharyngeal or vaginal colonization by Candida species. The combination of doxycycline and metronidazole, used for the same period, caused a significant increase of 2.5 log10 CFU/g of stools (mean) colonization by Candida. Likewise, 2 out of 9 patients treated with the combination had substantially increased colonization of their vagina by Candida species. This effect, however, could not be expressed statistically due to the semiquantitative nature of the vaginal cultures. In contrast, the combination did not increase oropharyngeal colonization. In conclusion, doxycycline and metronidazole as monotherapies, did not increase significantly Candida colonization in the cavities examined. The combination of doxycycline and metronidazole had a substantial effect, increasing the GI and vaginal colonization by Candida organisms.

Anti-Bacterial Agents↗
PubMed2002

Triplet combination with irinotecan plus oxaliplatin plus continuous-infusion fluorouracil and leucovorin as first-line treatment in metastatic colorectal cancer: a multicenter phase II trial.

PURPOSE: To evaluate the efficacy and tolerance of irinotecan (CPT-11) in combination with oxaliplatin (L-OHP) plus fluorouracil (5-FU)/leucovorin (LV) (de Gramont regimen) as first-line treatment of metastatic colorectal cancer (MCC). PATIENTS AND METHODS: Thirty-one patients with MCC who had not received prior therapy for metastatic disease were enrolled. Their median age was 60 years; performance status (World Health Organization) was 0 in 12, 1 in 14, and 2 in five patients; 19 patients (61%) had prior surgery, and 14 (45%) had adjuvant chemotherapy. CPT-11 was administered on day 1 at 150 mg/m(2) as a 90-minute intravenous (IV) infusion; L-OHP was administered on day 2 at 65 mg/m(2) as a 2-hour IV infusion; and on days 2 and 3, LV 200 mg/m(2) preceded 5-FU administration of 400 mg/m(2)/d initial IV bolus dose followed by 600 mg/m(2)/d 22-hour IV continuous infusion. The regimen was repeated every 2 weeks. RESULTS: All patients were assessable for toxicity and 30 for response to treatment. Complete response was achieved in two patients (6.5%) and partial response in 16 (51.6%) (overall response rate, 58.1%; 95% confidence interval, 40.7% to 75.4%); eight patients (25.8%) had stable disease, and five (16.1%) had disease progression. The median duration of response was 9 months, and the median time to disease progression was 13 months. Neutropenia grade 3 to 4 occurred in 14 patients (45%) and febrile neutropenia in two (6%). Diarrhea grade 3 to 4 was observed in 10 patients (32%), neurotoxicity grade 3 to 4 in three (9%), and asthenia grade 3 in two (10%). No treatment-related death has occurred. CONCLUSION: The triplet combination of 5-FU/LV + CPT-11 + L-OHP is a highly active regimen with manageable toxicity as front-line treatment in MCC.

Adult↗
PubMed2002

Common symptoms--different diseases: coexistence of neurosyphilis and non-Hodgkin's lymphoma.

We describe the case of a 32-year-old man with generalized lymphadenopathy who was diagnosed with a low-grade follicular small-cleaved cell lymphoma. The patient developed hearing loss, tinnitus and cerebrospinal fluid (CSF) pleocytosis attributed to central nervous system (CNS) infiltration by his malignancy, while receiving chemotherapy with vincristine, cyclophosphamide and prednisone. Despite intrathecal chemotherapy with methotrexate, the CSF pleocytosis persisted. Neurosyphilis was suspected because of prior history of gonorrhea and was confirmed with serologic studies of blood and CSF and from the decline of the anti-treponemal antibody titers with appropriate antibiotic therapy. Syphilis should be considered in the differential diagnosis of patients with generalized lymphadenopathy and neurologic signs or symptoms.

Adult↗
PubMed2002

Brachyspira (Serpulina) pilosicoli spirochetemia in an immunocompromised patient.

The case of an elderly immunocompromised man with non-Hodgkin's lymphoma who presented with fever, abdominal pain and bloody diarrhea is described. Brachyspira pilosicoli was isolated from culture. The patient was treated with penicillin G i.v. and became afebrile. B. pilosicoli is a recently recognized enteric pathogen of humans and animals. Intestinal spirochetosis should be included in the differential diagnosis of any immunocompromised or critically ill patient with dysentery.

Aged↗
PubMed2002

Cisplatin-etoposide alternating with topotecan in patients with extensive stage small cell lung cancer (SCLC). A multicenter phase II study.

PURPOSE: In order to investigate the feasibility of a potentially non-cross resistant drug regimen, we alternated cycles of cisplatin-etoposide with topotecan as front-line treatment in patients with extensive stage small cell lung cancer (SCLC). PATIENTS AND METHODS: Thirty-six previously untreated patients with extensive stage SCLC received cisplatin 75 mg/m(2) IV on day 1 and etoposide 100 mg/m(2) IV on days 1-3 on cycles one, three, five and seven and topotecan 1.5 mg/m(2) IV on days 1-5 on cycles two, four, six and eight. Cycles were repeated every 21 days. Patients' median age was 60 years and performance status (WHO) was 0 for 13, 1 for 20 and 2 for three patients. All patients were evaluable for response and toxicity. RESULTS: Five (14%) patients achieved a complete response and 18 (50%) a partial response for an overall response rate of 64% (95% confidence interval: 48.2-79.6%). After a median follow up of 10 months, the median duration of response was 5.5 months, the time to tumor progression 8 months and the probability of 1-year survival 48.9%. A total of 126 cycles of cisplatin-etoposide and 117 cycles of topotecan were administered with a median number of 4 cycles/patient for each regimen. There were no toxic deaths. Treatment delays due to toxicity occurred in 13 (10%) cycles after cisplatin-etoposide and 16 (14%) cycles after topotecan while doses were reduced in seven (6%) and five (4%) cycles, respectively. Grade 3-4 neutropenia, thrombocytopenia and febrile neutropenia complicated 13, 1 and 3% of cisplatin-etoposide cycles and 28, 6 and 1% of topotecan, respectively. Non-hematologic toxicity was mild. The delivered dose intensity was 96% for cisplatin and etoposide and 98% for topotecan. CONCLUSIONS: The alternating administration of cisplatin-etoposide and topotecan is a feasible, active and well-tolerated regimen in patients with extensive stage SCLC.

Adult↗
PubMed2002

Phase I study of weekly paclitaxel and liposomal doxorubicin in patients with advanced solid tumours.

The aim of this study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLT) of a weekly administration of paclitaxel and pegylated liposomal doxorubicin (Caelyx; Schering Plough Pharmaceutical) in patients with advanced solid tumours. 19 pretreated patients with solid tumours received escalated doses of pegylated liposomal doxorubicin (6-12 mg/m(2)) as a 1-h intravenous (i.v.) infusion followed by a fixed dose of paclitaxel (80 mg/m(2)) weekly for 4 consecutive weeks in cycles of 6 weeks. DLT was defined as grade 4 neutropenia or thrombocytopenia, febrile neutropenia, grades 3 or 4 non-haematological toxicity or treatment delay due to unresolved toxicity during cycle 1. The MTD was reached at the dose of pegylated liposomal doxorubicin of 10 mg/m(2)/week and paclitaxel of 80 mg/m(2)/week. The DLTs were treatment delay due to grade 3 neutropenia and grade 3 diarrhoea. A total of 55 chemotherapy cycles were administered, and grades 3-4 neutropenia occurred in seven cycles (13%); the non-haematological toxicity was mild with grades 2/3 diarrhoea occurring in 4 (7%), grades 2-4 asthenia in 11 (20%) and grade 2 mucositis in 7 (13%) cycles. There was no case with more than a 10% LVEF decrease after a median of 3 (range 2-6) administered cycles/patients. One patient with breast cancer and 1 with ovarian cancer experienced a major partial response. The weekly administration of pegylated liposomal doxorubicin at the dose of 10 mg/m(2) in combination with paclitaxel at the dose of 80 mg/m(2) for 4 consecutive weeks, in cycles of 6 weeks which represent the recommended doses for further phase II studies, is a well tolerated regimen, which merits further evaluation in tumours known to be sensitive to taxanes and/or anthracyclines.

Adult↗
PubMed2002

Environmental surveillance of filamentous fungi in three tertiary care hospitals in Greece.

The environmental fungal load (FL) of three hospitals was studied in representative regions in Greece (Thessalonika, Northern Greece, Athens, Central Greece and Heraklion, Southern Greece). Air, surfaces and tap water from high-risk departments were sampled monthly during one year. Air FL was [median (range)] 10.6 (1.2-37), 5.5 (3-28.8) and 7.7 (3.1-12.1) cfu/m(3) at Thessalonika, Athens and Heraklion, respectively. Air FL was lower in winter and higher in summer and autumn but seldom above acceptable levels. Aspergillus spp. constituted 70.5% of the filamentous fungi isolated. Aspergillus niger was the most prevalent species in the air of all the hospitals followed by Aspergillus flavus and Aspergillus fumigatus. The least contaminated departments were the intensive care units, whilst most contaminated were the solid organ transplantation in Athens and haematology departments in Thessalonika. No correlation between fungal species, season, hospital or departments was observed. Sixty per cent of all surfaces examined yielded filamentous fungi and/or blastomycetes. While no fungi were recovered from water in Thessalonika and Athens, one-third of the samples in Heraklion (apart from those of ICU) yielded multiple fungal species. The higher air FL in Thessalonika and Athens was recorded in departments located close to renovation works. These findings suggest that the air and surface FL fluctuates over the year, is due to varying fungal species, but does not differ greatly among hospitals. The variation among hospitals, as well as the role of hospital water fungal contamination and appropriate measures to eliminate it, need further study.

Air Microbiology↗
PubMed2002

Effects of erythromycin, clarithromycin, roxithromycin and azithromycin on murine gut colonization by Candida albicans.

Male Crl:CD1(ICR) BR mice were fed either chow containing Candida albicans or regular chow. The gastrointestinal tract of the C. albicans-fed mice was permanently colonized by the yeast. Groups of C. albicans-colonized mice were subsequently treated either with a macrolide (erythromycin, clarithromycin, roxithromycin or azithromycin) for 10 days or a normal saline solution (controls). Other controls included non-colonized mice receiving the same antibiotics or a saline solution. Our data are as follows: (i) C. albicans-colonized mice treated with each macrolide had highly significant increase in colony counts of C. albicans in their stools compared to C. albicans-colonized mice treated with saline only; (ii) discontinuation of macrolide treatment showed a trend towards lower colony counts, which was not statistically significant (colony counts were sustained even after discontinuation of antibiotic treatment); (iii) dissemination of C. albicans did not occur; (iv) mice fed regular chow treated with the study drugs or saline did not have any yeasts in their stools. In conclusion, oral erythromycin, clarithromycin, roxithromycin and azithromycin cause a modest increase of the C. albicans concentration of the gastrointestinal tract. This increase is not associated with a higher risk of disseminated candidiasis.

Animals↗
PubMed2002

Phase I study of paclitaxel (taxol) and pegylated liposomal doxorubicin (caelyx) administered every 2 weeks in patients with advanced solid tumors.

OBJECTIVES: Paclitaxel and doxorubicin are among the most active chemotherapeutic agents in various types of tumors. Pegylated liposomal doxorubicin (Caelyx) has a more favorable pharmacokinetic and toxicity profile than the free drug. We conducted a phase I study to determine the maximum tolerated doses (MTD) and the dose limiting toxicities (DLT) of the combination administered every 2 weeks in patients with advanced solid tumors. PATIENTS AND METHODS: Treatment consisted of escalating doses of Caelyx (12.5-17.5 mg/m2) administered as a 30-min intravenous infusion on day 1 and paclitaxel (90-115 mg/m2) as a 3-hour intravenous infusion on day 2 every 2 weeks without growth factor support. One cycle was considered as the administration of two consecutive treatments in 28 days. Twenty-six patients with histologically confirmed advanced stage solid tumors have been enrolled. Treatment was first-line treatment for 38% of patients, second-line for 31% and third-line for 31%. RESULTS: The DLT were evaluated during the first 4 weeks of treatment (2 treatment administrations) and consisted in all but one case of grade 2-3 neutropenia resulting in treatment delay. One patient died of cardiac arrest 1 day after the first treatment. A total of 86 cycles have been administered with only 1 episode of febrile neutropenia. Hematologic toxicity was generally mild. Only 1 patient at the first and another at the highest dose level developed grade 4 neutropenia. At the highest dose level, 3 of 6 patients developed grade 3 neutropenia. Grade 4 anemia or grade 3-4 thrombocytopenia was not observed. Non-hematologic toxicity included grade 2-3 nausea/vomiting in 10%, grade 2-4 diarrhea in 7% and grade 2-3 neurotoxicity in 8% of cycles. Mucositis grade 3 complicated 1 cycle. Palmar-plantar erythrodysesthesia grade 2-3 was observed in 3 patients and was the reason for treatment discontinuation in 1 patient. Cardiotoxicity as the development of congestive heart failure or more than 10% reduction in left ventricular ejection fraction was not observed. The most common non-hematologic toxicity was grade 2-3 asthenia complicating 31% of the cycles. Among 18 evaluable patients, 1 complete and 4 partial responses were observed primarily in patients with breast cancer. The MTD which are the recommended doses for further use in phase II trials were Caelyx 15 mg/m2 on day 1 and paclitaxel 115 mg/m2 on day 2 administered every 2 weeks. CONCLUSION: The administration of Caelyx and paclitaxel every 2 weeks is a feasible regimen and is associated with acceptable toxicity.

Aged↗
PubMed2002

Docetaxel in combination with dacarbazine in patients with advanced melanoma.

OBJECTIVES: The number of agents that are active in patients with metastatic melanoma is limited and cure is not a realistic objective for treatment at this stage. The aim of the study was to evaluate the efficacy and safety of new combination regimen cosisting of docetaxel and dacarbazine (DTIC), as first-line chemotherapy, in patients with advanced melanoma. PATIENTS AND METHODS: Patients with advanced melanoma (including cerebral metastases) were eligible. Docetaxel 80 mg/m(2), i.v. over 1 h infusion on day 1, and DTIC 400 mg/m(2), i.v. over 45 min on days 1 and 2, were given every 21 days, for six cycles. All patients were premedicated, prior to each course, with methylprednisolone per os. RESULTS: Forty-one patients entered the study. Thirty-nine were assessable for response and 40 for toxicity. Objective responses were seen in 10 patients (24% of the eligible; 95% CI = 12.4-40.3%, 26% of the assessable and 28% of patients with cerebral metastases were excluded). Three of them achieved a complete response (7%; 95% CI = 1.5-19.9) and 7 a partial response (17%; 95% CI = 7.1-32.0), while 8 patients demonstrated stabilization of their disease (20%; 95% CI = 8.8-34.9). After a median follow-up of 20 months, the median time to progression was 7 months (range 0.5-22) and the median survival was 10 months (1-24+). The main toxicity (G3-4) was neutropenia which occurred in 8/40 (20%) patients. Additional patients had reversible G3-4 toxicities including alopecia, nausea and vomiting and fatigue; 3 of them presented mild to moderate hypersensitivity reactions to docetaxel. No toxic death was noted. CONCLUSIONS: The combination of docetaxel and DTIC is active and well tolerated in patients with advanced melanoma. While this combination is at least as effective as various combination regimens, it does not differ from that reported for single-agent DTIC.

Adult↗
PubMed2002

Peripheral primitive neuroectodermal tumour during pregnancy.

The case of a 25-year-old primipara in the second trimester of pregnancy, suffering from a peripheral primitive neuroectodermal tumour (pPNET) diagnosed by bone biopsy, is described. External irradiation was initially performed because of Jacksonian seizures due to a lesion in the right cerebral hemisphere. Appropriate shielding was used to reduce fetal exposure during brain radiotherapy. Caesarian delivery at the 27th week of gestation was performed because of tumour progression. The neonate had no evidence of disease and survived for 1 month. However, the placenta and ovaries showed metastases from the maternal pPNET. The patient died 14 months after initial diagnosis owing to the aggressiveness of the tumour, the rapid and extensive semination (bone marrow, lung, liver, craniospinal axis involvement) and the inability to adequately treat the patient with appropriate doses of chemotherapy.

Adult↗
PubMed2001

Comparison of docetaxel/cisplatin to docetaxel/gemcitabine as first-line treatment of advanced non-small cell lung cancer: early results of a randomized trial.

The study compares docetaxel plus cisplatin (DC) and docetaxel plus gemcitabine (DG) regimens for the treatment of advanced non-small cell lung cancer (NSCLC). Patients were randomized to receive either the DC or the DG combination. They were stratified according to age, performance status (PS) and stage of disease. Three hundred seventeen patients entered the study. Of them, 162 received the DC regimen and 155 the DG regimen. There were no differences in the patients' characteristics between the two study arms. Preliminary analysis included 132 evaluable patients in the DC arm and 114 in the DG arm. Three complete responses (CR) (2.3%) and 39 partial responses (PR) (30%) were documented in the DC arm (response rate (RR) 32.3%; 95% CI 23.87-39.76%), whereas 1 CR (0.9%) and 38 PR (33%) were documented in the DG arm (RR: 33.9%; 95% CI 25.5-42.92%). No differences in the RR, response duration, time to tumor progression, overall survival and 1-year survival were observed between the two groups. Regarding toxicity, there were no significant differences in grade 3-4 anaemia and thrombocytopenia between the two arms. However, grade 3-4 neutropenia occurred in 40 patients (33%) treated with the DC regimen and in 31 patients (22%) treated with the DG regimen (P=0.01). Twenty-four (16%) patients in the DC arm and 20 (14%) in the DG arm developed febrile neutropenia. There was one death due to sepsis in each arm. Non-haematological toxicity was mild and equal in the two arms, with the exception of grade 3-4 nausea and diarrhoea, which were more frequent in the DC arm. In conclusion, preliminary results showed that the DG regimen was as effective as the DC regimen. The toxicity profile of the DG combination was relatively milder. Hence, cisplatin cannot be considered longer as a mandatory component of chemotherapy against NSCLC.

Adult↗
PubMed2001

The impact of norfloxacin, ciprofloxacin and ofloxacin on human gut colonization by Candida albicans.

We studied gastrointestinal (GI) colonization by Candida albicans in patients receiving oral norfloxacin, ciprofloxacin or ofloxacin as monotherapy for urinary tract infections. Quantitative stool cultures for C. albicans were performed before, at the end and 1 week after the end of treatment. All 3 quinolones increased GI colonization by C. albicans. Ciprofloxacin caused the highest increase, which was not statistically significant.

Adult↗
PubMed2001

A dose-finding study of the weekly administration of paclitaxel in patients with advanced solid tumors.

The purpose of this study was to determine the dose-limiting toxicities and the maximum-tolerated dose (MTD) of weekly administration of paclitaxel in patients with advanced solid tumors. Twenty-six patients with advanced solid tumors were treated with escalated doses of paclitaxel (starting dose 70 mg/m(2)/wk with increments of 10 mg/m(2)/wk) for 4 consecutive weeks every 6 weeks. No intrapatient escalation or growth factor support was allowed. The DLT was exceeded at the dose of 120 mg/m(2)/wk, and the dose-limiting events were grade IV neutropenia and treatment delay because of incomplete hematologic recovery. There was no cumulative myelosuppression. Grade IV neutropenia occurred in four (6%) cycles, and there was one episode of febrile neutropenia. Grade II/III fatigue occurred in 19 (73%) patients, resulting in discontinuation of treatment in 2 of them; grade II neurosensory toxicity and grade II alopecia occurred in 8 (31%) patients each. The MTD, which is also the recommended dose for further phase II studies, was 110 mg/m(2)/wk. Among the 21 patients with bidimensionally measurable disease, 2 (10%) partial responses were observed, both in patients with heavily pretreated advanced breast cancer. The weekly administration of paclitaxel for 4 consecutive weeks in cycles of 6 weeks is a feasible, safe, and active outpatient regimen that merits further evaluation in combination with other anticancer agents.

Aged↗
PubMed2001

Infectious complications of purine analog therapy.

Patients with lymphoid malignancies such as chronic lymphocytic leukemia, particularly those who receive the newer purine analogs, are at increased risk for infectious morbidity and mortality. Defects in cell-mediated immunity appear to be a major predisposing factor in these patients. An expanding spectrum of pathogens associated with lymphocytopenia and depletion of CD4 has been described in the setting of therapy with purine analogs. During the past 2 years new knowledge about the immunosuppression related to that treatment has continued to accumulate.

Antimetabolites, Antineoplastic↗