Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to improve loco-regional control in locally advanced oropharyngeal carcinoma, a phase II trial was designed to establish the feasibility of concomitant conventional radiotherapy and three cycles of chemotherapy at day 1, 21 and 42 with cisplatin (CDDP) 20 mg/m2 and 5-fluorouracil (5-FU) 400 mg/m2 day 1 to day 4, and mitomycin C (MMC) 10 mg/m2 day 1. From March 1990 to September 1993, 27 patients (mean age: 55) were included in this study. Three patients (11%) were T2N0, 19 (70%) T3 (T3N0: n = 9, T3N1: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4N0: n = 1, T4N1: n = 1, T4N2: n = 2, T4N3: n = 1). With a mean follow-up of 34 months (17-59), ten patients (37%) were alive, free of disease; among the 17 other patients, seven died with cancer. Loco-regional control rate was 85%. One and 2-year survival rates were respectively 48 and 31% for overall and disease-free survival; respective corrected overall survival rates were 68 and 61%. Grade 3 or 4 mucositis was 81%; enteral feeding was necessary for 63% of the patients; mean loss of weight was 5.7 kg. Grade > 2 thrombopenia occurred in 11 patients (41%), grade > 2 neutropenia in eight patients (29%) , grade > 2 anemia in four patients (15%). Febrile neutropenia or aplasia occurred in five patients (19%). Two patients (7%) died during treatment of haematological or infectious complications related to the treatment. Another patient died 2 months after treatment with grade 4 thrombopenia and septicemia. Addition of MMC to 5-FU and CDDP might have been partly responsible of this increased toxicity. A high complete response rate has been achieved with this concomitant radio-polychemotherapy, but with a severe digestive and haematological toxicity, which did not allow to conclude to the feasibility of this therapeutic association.
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PMID:[Concomitant radiochemotherapy with cisplatin (CDDP), 5-fluorouracil (5-FU) and mitomycin C (MMC) in locally advanced carcinoma of the oropharynx. Results of a phase II trial]. 874 71

Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase II studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m(-2) and ifosfamide doses from 2.5 to 5.0 g m(-2). Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m(-2) of docetaxel combined with 5.0 g m(-2) ifosfamide appeared to be manageable. Schedule A was advocated for further treatment.
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PMID:Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours. 1064 11

Docetaxel is a new antimicrotubule agent that has been shown to be active against a variety of solid tumors. Ifosfamide is an alkylating drug that has demonstrated activity against non-small cell lung cancer, testicular cancer, breast cancer, and soft tissue sarcoma. This phase I study of the combination of these drugs was performed to assess the feasibility of using the two agents together, to determine the maximum tolerated dose and the side effects, and to propose a safe schedule for further phase II studies. Thirty-four patients with histologically confirmed solid tumors who had not been treated previously with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-hour infusion followed by ifosfamide as a 24-hour infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg/m2 and ifosfamide doses from 2.5 to 5.0 g/m2. Grades 3 and 4 granulocytopenia were observed in 89% of courses and appeared to be of short duration and related to the ifosfamide dose. Febrile neutropenia and sepsis occurred in 17% and 2% of courses, respectively. Severe anemia and thrombocytopenia were uncommon. Nonhematologic toxicities were mild to moderate, and included alopecia, nausea, vomiting, mucositis, diarrhea, sensory neuropathy, skin and nail toxicity, hypersensitivity reactions, and edema. Schedule B appeared to induce more gastrointestinal toxicity than schedule A. One complete response in soft tissue sarcoma and two partial responses, one in cancer of unknown primary and the other in non-small cell lung cancer, were documented. The dose-limiting toxicity for schedule A was neutropenic fever at a dose of 85 mg/m2 docetaxel and 5 g/m2 ifosfamide. The dose-limiting toxicity for schedule B was neutropenic fever at a dose of 75 mg/m2 docetaxel and 4 g/m2 ifosfamide. A dose of 75 mg/m2 docetaxel combined with 5 g/m2 ifosfamide according to schedule A can be recommended for further studies.
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PMID:Docetaxel and ifosfamide in patients with advanced solid tumors: results of a phase I study. 953 8

The purpose of this study was to evaluate the combination of cisplatin and vinorelbine (PVn) for relapsed and chemotherapy-pretreated metastatic breast cancer. Twenty-three patients with metastatic breast cancer and prior chemotherapy were entered in a phase II study between June 1993 and December 1994. Eleven patients were premenopausal and 12 were postmenopausal. Follow-up data up to June 1997 are presented. All patients received cisplatin at a dose of 90 mg/m2 divided over 3 days as 30 mg/m2 infused over 4 hours. Intravenous vinorelbine 25 mg/m2 was given on days 1 and 8 or 15 according to patients' blood counts. Cycles were given every 3 to 4 weeks. An overall response rate of 61% (16/23 patients) was observed. Complete remission was obtained in six patients (26%) and partial remission was obtained in nine patients (35%). The duration of response ranged from 3 to 9 months, with an average of 4 months. Stable disease was noted in 29.1% and progressive disease in 8.3%. Overall survival at 12 months was 50%, and at 36 months it was 8%. Five of 12 patients (42%) who had prior doxorubicin therapy responded well to cisplatin-vinorelbine. Of those 12, seven were refractory and progressive on a doxorubicin-containing regimen, one had complete remission, and four had partial remission. Hematologic toxicity was acceptable. Treatment was delayed because of neutropenia in nine cycles (9.2%) and grade 2 leukopenia occurred in 54% of cycles. Febrile neutropenia occurred in seven cycles (7.1%), and five cycles were complicated by documented sepsis (5.1%). No treatment-related mortality occurred. Thrombocytopenia (grade 3) was seen in 27% of cycles, with no patient having a platelet count below 50,000 or bleeding episodes. Other toxicities were not major or dose-limiting. In conclusion, the combination of cisplatin and vinorelbine produced good responses: 61% response rate (16 of 23 patients) in relapsed, refractory, and heavily pretreated metastatic breast cancer, with 50% survival at 1 year, 12% at 2 years, and 8% at 3 years. In addition, a response rate of 42% (5 of 12 patients) was seen in patients resistant to anthracyclines.
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PMID:Combination cisplatin-vinorelbine for relapsed and chemotherapy-pretreated metastatic breast cancer. 1036 41

A group of 51 patients with multiple myeloma, non-Hodgkin's lymphoma or Hodgkin's disease receiving high-dose chemotherapy and autologous peripheral blood stem cell rescue received chemotherapy and clinical care in the peritransplant period at home. This group was compared with 88 cases with the same diagnoses, receiving the peripheral stem cell transplant over the same time period as an inpatient in a high efficiency particulate air filtered bone marrow transplant unit. Patients were treated at home based on choice, geographic accessibility, availability of an educated care giver and a clean home environment, and comprehension of the concepts of infection and aseptic techniques. Febrile neutropenia and sepsis were not increased in the home group and no episodes of septic shock were seen in this group. Patients at home received prophylactic oral ciprofloxacin and roxithromycin during the phase when the absolute neutrophil count was < 1 x 10(9)/l. Fewer gram-negative infections, but no diminution in gram-positive infections or in the rate of fever were seen in patients at home. Empiric therapy with a third generation cephalosporin, teicoplanin and tobramycin was instituted in 31 patients who developed a fever greater than 38.5 degrees C. Of this group of 31, 18 required admission to hospital, 12 because of febrile neutropenia which persisted or was considered unsuitable for management at home due to sepsis. The remaining 13 with febrile neutropenia remained at home throughout, as did the 20 cases not developing neutropenic fever. This study demonstrates the feasibility of managing carefully selected patients in their home environment when at risk from febrile neutropenia or other septic complications following autologous peripheral stem cell support.
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PMID:Infections in patients managed at home during autologous stem cell transplantation for lymphoma and multiple myeloma. 1064 11

The therapy of patients with relapsed or refractory indolent lymphoma relies on the development of new drug combinations. The drugs bendamustine and fludarabine have cytotoxic activity as monotherapy in indolent lymphoma and show synergism in vitro. In this study, we combined both drugs in a multicenter clinical phase I/II trial to evaluate their toxicity and efficacy. Bendamustine was given at 30 or 40 mg/m2/d (dose levels 1 and 2), fludarabine at 30 mg/m2/d, each drug on days 1 to 3. Six cycles were to be given every 4 weeks. A total of 29 patients with relapsed or refractory indolent lymphoma were included in the study. During phase I, 9 patients were treated at dose level 1 and 7 patients at dose level 2. Thirteen patients were added to the study during phase II. Fourteen patients had follicular lymphoma, 11 patients mantle cell lymphoma, 2 patients lymphoplasmocytic and 2 patients nodal marginal zone lymphoma. Median age was 62 years (range 39-74). All patients were in stages III or IV of their disease and had received prior chemotherapy with or without additional radio- or immunotherapy. The dose limiting toxicity was hematotoxicity in all cases and occurred in 3 of 7 evaluable patients at dose level I and in 3 of 7 patients at dose level 2. One patient at dose level 2 died of sepsis in neutropenia with persistent thrombocytopenia. The study was continued at dose level 1 (phase II). Analysis of 19 evaluable patients treated at dose level 1 reveiled hematotoxicity CTC grade III in 47% and grade IV in 26%. Neutropenic fever occurred in 4 patients (21%). On an intent-to-treat basis, 45% or 32% of all patients at dose level 1 reached CR or PR, respectively. Nine of 9 patients with mantle cell lymphoma responded to therapy. The overall response rate was 77%. Eight of 15 responders relapsed after a median follow-up time of 14 months (range 2-43). The major complication of fludarabine in combination with bendamustine is hematotoxicity. Dose level 1 with 30 mg/m2/d of both drugs on days 1 to 3 was defined as the recommended dose. Despite unfavorable prognostic features (histologic subtype, stage of disease, pretreatment) response rates were good with this regimen.
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PMID:Fludarabine and bendamustine in refractory and relapsed indolent lymphoma--a multicenter phase I/II Trial of the east german society of hematology and oncology (OSHO). 1522 42

A phase II trial at 12 institutions using AT (doxorubicin 60 mg/m2 plus docetaxel 60 mg/m2) given every 21 days was conducted. Eighty-nine patients were entered who ranged in age from 25 to 75 years, 41.6% of whom had stage IIIB disease and 58.4% of whom had stage IV disease. Among the patients with stage IV disease, 32.7% had received prior adjuvant chemotherapy. Premedication with dexamethasone (8 mg orally twice per day for 3 days) and prophylactic ciprofloxacin (500 mg orally twice per day on days 5-15) was used. Colony-stimulating growth factors were reserved for secondary prophylaxis after prolonged or febrile neutropenia (FN) or documented severe infection in an earlier cycle. After a cumulative dose of doxorubicin of 480 mg/m2, patients could continue to receive docetaxel (100 mg/m2) alone. Median time on study as of July 6, 2003, was 54 months. Febrile neutropenia occurred in 36 patients (41.9%): 23 developed FN in the absence of previous prophylactic growth factor support and 13 developed it despite previous growth factor support. One patient died from sepsis. Other grade 3/4 adverse events included nausea in 3.5%, vomiting in 4.7%, stomatitis in 8.1%, diarrhea in 5.8%, arthralgia/myalgia in 2.3%, fluid retention in 1.2%, pulmonary embolism in 1.2%, rest dyspnea in 1.2%, neuromotory toxicity in 1.2%, and neurosensory toxicity in 1.2%. Clinical congestive heart failure was seen in 2 patients (2.3%). Sixty-seven patients were evaluable for best response with 6 cycles of therapy. Fourteen patients (20.9%) had a complete response and 30 (44.8%) had a partial response, for an overall response rate of 65.7% in evaluable patients. The median response duration was 25.9 months, and the median time from entry to progression or death was 27.5 months. The median survival time for the 86 patients with endpoint information was 31.1 months. The administration of AT with primary ciprofloxacin and secondary colony-stimulating factor prophylaxis is feasible, and the combination is active. Its value in the adjuvant setting is currently under investigation.
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PMID:Phase II trial of a doxorubicin/docetaxel doublet for locally advanced and metastatic breast cancer: results from national surgical adjuvant breast and bowel project trial BP-57. 1533 53

To evaluate the efficacy and safety of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma (NPC). Nineteen previously untreated metastatic NPC patients received one to six cycles of docetaxel and cisplatin. Fifteen patients received at least three cycles. The starting dose was 75 mg/m2 every three weeks for both drugs in 15 patients, and 60 mg/m2 for both drugs in four patients. All patients were included in toxicity and survival analysis, and 16 patients were evaluable for response. Median follow-up time was 11.6 months. Hematological toxicity was severe with Grade 4 neutropenia in 78.9% patients and 51.3% cycles. Febrile neutropenia occurred in 42% patients and 12.5% cycles, with two septic deaths in the population treated with 75 mg/m2. Patients treated with a dose subsequently reduced to 60 mg/m2 had a lower incidence of Grade 4 neutropenia and no incidence of neutropenic fever/sepsis. Overall response rate was 62.5%, with a 95% confidence interval of 35-85%. Partial and complete response rates were 56.3% and 6.3%, respectively. Median time to progression was 5.6 months and median survival was 12.4 months. Three patients (15.6%) survived >2 years following chemotherapy. The combination of docetaxel and cisplatin is active in metastatic NPC. The dose of 60 mg/m2 for both drugs without colony-stimulating factor support should be further evaluated as a high incidence of febrile neutropenia was observed with 75 mg/m2 dose.
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PMID:A phase II study of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma. 1597 21

Febrile neutropenia is common in children with leukemia. Mucous membrane and skin are most common portals of entry for microorganisms in these patients. The aim of the present study was to find the prevalence of mucocutaneous findings infebrile neutropenic leukemic children. The authors prospectively examined children with fever with neutropenia in acute leukemia, aged 1-15 years, who were admitted to the Department of Pediatrics, King Chulalongkorn Memorial Hospital, between September 2000 and August 2001. During the study period, 46 children had 116 admissions, 51 of which were due to febrile neutropenia. Their cancer diagnoses were ALL (76%) and ANLL (24%). The prevalence of mucocutaneous findings was 86% (61% were from infections, 22% from mucositis and 4% from chemical phlebitis). Other detected sites of infection were lower respiratory tract (36%), urinary tract (32%), upper respiratory tract (11%), septicemia (11%) and unidentified (35%). Thirty-four percent of the patients had more than one site of infection. Gram-negative septicemia was the most common infection (15cases/71%) followed by gram positive (4cases/19%) and candida (2cases/10%). The prevalence of infection was found in severe neutropenia (absolute neutrophil count, ANC less than 500 cell/cu mm), moderate neutropenia (ANC, 500-1000 cell/cu mm) and mild neutropenia (ANC, 1001-1500 cell/cu mm) was 72%, 9% and 5%, respectively. Infection in patients in the severe neutropenia group was significantly more common than in moderate mild neutropenia groups (p < 0.01). Seven patients (15%) died, all of them had severe and prolonged neutropenia, for more than 7 days. Daily physical examination of skin and mucous membrane are suggested for proper and prompt diagnosis and treatment of febrile neutropenic children with acute leukemia to reduce mortality and morbidity in these patients. A Guideline for the use of antimicrobial agents in neutropenic patients with acute leukemia is proposed In conclusion, infection was commonly found in severe neutropenia. Mucocutaneous infection was the most common site of infection infebrile neutropenia in children with leukemia.
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PMID:Mucocutaneous findings in febrile neutropenic children with acute leukemias. 1608 22

The objective of this study was to evaluate etiology and consequences of neutropenic fever in AML patients. Two hundred and ninety neutropenic periods following chemotherapy in 84 AML patients were retrospectively evaluated. Neutropenic fever was found in 280 periods (97%). Severe sepsis developed in 35 occasions (13%) and 9 patients (11%) died due to severe sepsis. In 165 episodes with neutropenic fever (59%), the potential causative organism was found in blood cultures. Gram-negative bacteria were more commonly found in patients who developed severe sepsis (40% vs. 23%, p = 0.03). CRP after 2 - 3 days from start with fever was higher in patients with severe sepsis (190 mg/L vs. 96 mg/L, p < 0.001) but the rise in CRP rather coincided than preceded with the development of severe sepsis. Severe sepsis is associated with significant mortality in AML patients. Earlier methods than CRP are needed to predict development of severe sepsis.
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PMID:Neutropenic fever and severe sepsis in adult acute myeloid leukemia (AML) patients receiving intensive chemotherapy: Causes and consequences. 1829 12


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