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)

Eighteen patients with metastatic non-small cell lung cancer were treated with a combination of intravenous vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) 25 mg/m2 on days 1 and 8 and intravenous paclitaxel 175 mg/m2 on day 2 every 3 weeks. All patients were given granulocyte colony-stimulating factor 5 micrograms/kg/d subcutaneously on days 3 through 7 and 9 through 17 or until the absolute neutrophil count reached 10 x 10(9)/L or higher. One patient was enrolled in this study too recently to be assessed. The mean age of the remaining 17 patients was 59 years (age range, 33 to 75 years); all but one patient had refractory disease, mostly to cisplatin-containing regimens. Four patients were ineligible (two because of poor performance status and two because of previous exposure to vinblastine). Three partial responses were observed, with durations of 46, 64, and 140+ days. Four patients had stable disease and four had progressive disease. The most common side effect was neutropenia (five grade 4 and one grade 3); two patients died of leukopenic sepsis in the first cycle. Peripheral neuropathy was also common (four grade 1 and one grade 2 sensory neuropathy). Other toxic effects were anemia and nausea and vomiting. The median survival was 153 days in all patients and 179 days in eligible patients. The preliminary results in this ongoing study of combination vinorelbine and paclitaxel as second-line therapy for metastatic non-small cell lung cancer are promising, and using this regimen as first-line therapy is warranted.
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PMID:Pilot study of vinorelbine (navelbine) and paclitaxel in patients with refractory non-small cell lung cancer. 861 Feb 31

Most patients with advanced solid tumors of the chest will have local and/or distant disease progression despite standard therapy. Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) is a new semisynthetic vinca alkaloid with single-agent activity in lung cancer that recently also has been shown to act as a radiosensitizer in vitro. This study aims to define the maximum tolerated dose and dose-limiting toxicity when vinorelbine is given with cisplatin and concomitant radiation therapy. To date, 25 patients with advanced malignancies of the chest have been treated in a dose-escalation trial of vinorelbine administered once weekly with cisplatin (100 mg/m2 every 21 days) and concomitant thoracic radiation therapy (2 Gy/d x 30 fractions for 60 Gy). Vinorelbine was initially given at 20 and 25 mg/m2/wk. Acute dose-limiting toxicity was myelosuppression, which was seen at a vinorelbine dose of 25/mg/m2/wk, with grade 4 neutropenia in two of three patients and one treatment-related death from neutropenic sepsis. At vinorelbine 20/mg/m2/wk, no acute dose-limiting toxicity was seen, but grade 3 or 4 esophagitis developed in three of six patients near the end or after completion of radiation therapy. We subsequently decreased the administration of vinorelbine to weeks 1, 2, 4, and 5. Tolerance appears to be greater with this schedule; however, severe or life-threatening esophagitis at the completion of therapy continues to be observed. Given these preliminary results, it appears feasible to treat patients with advanced chest malignancies with concomitant cisplatin, vinorelbine, and radiation therapy. The significant dose reduction of vinorelbine that is necessary with concomitant radiation therapy provides the first in vivo evidence of a strong radiosensitizing effect of vinorelbine. The schedule is currently being modified to reduce the incidence of esophagitis.
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PMID:Vinorelbine (Navelbine), cisplatin, and concomitant radiation therapy for advanced malignancies of the chest: a Phase I study. 861 Feb 37

This study involved 25 elderly (> 65 years old) patients (pts) with unresectable non small cell lung cancer (NSCLC) who were not eligible for polychemotherapy. The diagnosis of NSCLC was histologically or cytologically documented, and all of them had measurable or evaluable disease. The median age of the patients was 71 (range 65-77); 9 had been pretreated. The pts received 25 mg/m2 of vinorelbine weekly or bi-weekly depending on the results of blood tests. The treatment continued until disease progression or tolerance. No complete response was achieved: 3 pts (12%) had a partial response (RP) (8-12-14 months), 13 (52%) stable disease (SD) with an improvement in symptoms, such as cough and/or pain, and 9 pts (36%) progressed. Compliance with the therapy was acceptable. The main toxicity was hematological: neutropenia was observed in 16 pts, with only 1 case of grade 4 neutropenia without sepsis; grade 1-2 anemia occurred in 8 patients. The other toxicities included grade 1-2 neurotoxicity in 8 pts, chemical phlebitis in 2 pts and grade 3 cardiotoxicity reversible with medical treatment in 1 patient. The median survival time was 10 months (lower quartile 5 months, upper quartile 23 months) (Kaplan and Meyer method). Vinorelbine can be considered a rational choice in elderly pts with advanced NSCLC who are not suitable for aggressive polychemotherapy, with the aim of improving their quality of life in terms of symptoms and outpatient treatment.
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PMID:Vinorelbine chemotherapy in non small cell lung cancer: experience in elderly patients. 926 13

Forty patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated weekly with vinorelbine 30 mg/m2. Thirty-five patients received prior surgery, 20 prior chemotherapy, and 38 prior radiation therapy. Five patients were not evaluable for response and were assumed to be nonresponders. There were three confirmed responders (one complete response, two partial responses) for a response rate of 7.5% (95% confidence interval, 1.6%-20.4%). The median survival time for all patients was 5 months (range, 0.5-50 months), the median progression-free survival time was 2 months (range, 1-49 months). The most common toxicity was myelosuppression, with 60% of patients experiencing grade 3 or higher leukopenia. There was one treatment-related death resulting from sepsis. Vinorelbine has minimal activity in patients with SCCHN that does not exceed that of other currently used agents.
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PMID:A phase II trial of vinorelbine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. 970 41

Advanced non-small cell lung cancer (NSCLC) denotes those of TNM stage III and IV. NSCLC has its specific characteristics in respect of oncological behaviour, molecular biology, sensitivity to chemotherapy (CT) and radiotherapy (RT), and requires different therapeutic strategies in comparison with small cell lung cancer. The therapies include: (1) surgery in combination with new effective drugs is resulted in improved RR from 15% a decade ago to 40-60% today. Cisplatin (C-DDP) is the most attractive drug in the treatment of NSCLC, in lengthening the life-span of Stage IV NSCLC patients and as an indispensable sensitizer in RT. Taxinol, Gemcitabine (GEM), Navelbine (NVB), Edatrexate (ETX), CPT-11 and high dose Epirubicin (EPI HD) are recommended as new effective drugs. Response rates recently reported for the combination CT with the drugs mentioned above for NSCLC are from 30-65%, and with 8-42 weeks of MST. Induction or neoadjuvant therapies for advanced NSCLC, with 40-69% of RR, 25-29% of complete resection rate, 8-34% of CR and 17-45% of one year SR are reviewed. Eight random studies comparing MST between CT with C-DDP and best supportive care for NSCLC are statistically significant. (2) RT for Stage III NSCLC with 2 year and 5 year survivals of 20 and 5% respectively. Although such outcome is hardly acceptable, RT sensitizer, modified RT techniques and chemoradiotherapy (CRT) are imperative to improve the effect of RT in advanced NSCLC. Clinical literature suggest that CRT is better than RT, though without marked difference. Further studies and sufficient follow-up are necessary to judge the efficacy in terms of long-term survival and toxic reaction. (3) Biological therapy: gene therapy of NSCLC is still in the experimental and developmental stage. Of biological response modifier (BRM), alpha IFN in 11 cases of NSCLC with RR of 9% and MST of 14 months, IL-2 and LAK cell treatment in 11 cases with RR of 9% and MST of 18 months are reported. Instillation of BRM such as IL-2 or alpha-IFN into the pleura after drainage of cancerous effusion has been reported as the most effective for those whose RR is of 80-90% and the clinical response time is fairly long. Hematological cytokine as a protective adjuvant therapy against CT/RT toxicity makes high dose of CT possible and raises the response and patient tolerance. In multimodality therapy, it plays an important role to reduce post CT infection and septicemia.
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PMID:Non-surgical therapy for patients with advanced non-small cell lung cancer. 976 13

Vinorelbine, docetaxel and cisplatin have documented single-agent activity in non-small-cell lung cancer (NSCLC); a multicenter phase II trial was initiated in order to evaluate the tolerance and efficacy of their combination. A total of 24 chemotherapy-naive patients with measurable stage IIIB or IV NSCLC and performance status (PS; WHO) 0-2 entered the study. Vinorelbine (20 mg/m2 i.v.) was given on days 1 and 15, cisplatin (60 mg/m2) on day 1, and docetaxel (100 mg/m2) on day 16, in cycles of 28 days. Recombinant human granulocyte colony-stimulating factor (150 microg/m2 s.c.) was administered prophylactically from day 17 to day 27. One pathological complete (4%) and six partial responses (25%) were documented (overall response 29%; 95% CI 11.6-49.2%). A total of five patients (21%) had stable and 12 (50%) progressive disease. The median duration of response was 28 weeks and the median time to tumor progression 36 weeks; the median survival was 20 weeks. Grade 3-4 neutropenia occurred in 16 patients (67%) while 13 of them (54%) developed febrile neutropenia. Grade 4 mucositis occurred in two patients (8%) and one of them also presented grade 4 diarrhea. There were four treatment-related deaths: two from sepsis, one from massive hemoptysis due to a pulmonary abscess and one from acute myocardial ischemia 7 days post-chemotherapy. In conclusion, the high incidence of neutropenic episodes and treatment-related deaths led to an early discontinuation of patient enrollment. This combination, in the schedule and the doses used, could not be recommended for off protocol treatment of patients with advanced NSCLC.
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PMID:Combination chemotherapy with docetaxel, vinorelbine and cisplatin as first-line treatment of advanced non-small-cell lung cancer: a multicenter phase II study of the Greek Cooperative Group for Lung Cancer. 985 99

A phase II study was conducted to assess the toxicity and response rate of vinorelbine (NavelbineR) combined with epirubicin and fluorouracil (NEF) in metastatic breast cancer. Vinorelbine was delivered at a dose of 25 mg/m2 on days 1 and 8, epirubicin at 60 mg/m2 on day 1 and fluorouracil at 600 mg/m2 on day 1, at 3-week intervals. Forty consecutive ambulant patients with breast cancer with measurable metastases were treated with a total of 310 cycles (median 8) as first-line therapy. The objective response rate was 83% (95% CI 71-95) (6/40 CR 15%, 27140 PR 68%). In 3 patients, CNS metastases were detected during NEF therapy those who had a partial response in their visceral metastases. Median time to progression was 13 months (95% CI 7-19) and estimated median survival time was 32 months. The main dose-limiting adverse effect, grade III-IV haematological toxicity, was reported in 92% of patients. One patient died of neutropenic sepsis. Grade III infections requiring hospitalization were observed in 8 patients (20%). Half of the patients complained of mild constipation, nausea or stomatitis, which were easily managed. Almost all patients had grade III alopecia. One patient with previous adjuvant anthracycline therapy (CEF x 9 two years earlier) developed fatal grade IV cardiac failure associated with pulmonary emboli 2 months after completion of NEF therapy (PR with 6 cycles). In line with the observations of others conducting phase II first-line trials combining vinorelbine and epirubicin, it is concluded that the NEF regimen is effective in metastatic breast cancer. Haematological toxicity, however, requires dose reductions in many patients. Furthermore, careful monitoring of cardiac function is necessary, particularly in patients who received prior adjuvant anthracycline therapy.
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PMID:Vinorelbine, epirubicin and fluorouracil as first-line therapy in metastatic breast cancer--a phase II trial. 1289 2

Small-cell lung cancer that progresses after initial response may still be sensitive to systemic treatment. This study assessed doxorubicin plus vinorelbine tartrate (Navelbine Injection) in patients who had no prior exposure to these agents. Treatment consisted of vinorelbine at 25 mg/m2 on days 1 and 8 and doxorubicin at 50 mg/m2 on day 1 of each 21-day cycle. The trial was stopped early because of excessive toxicity. The partial response rate was 26.7%. Toxicities included grade IV neutropenia in 73%, and febrile neutropenia and/or sepsis in 60%. Three patients died from sepsis during cycle 1. Performance status 2 was significantly associated with febrile neutropenia (p = 0.044). Although this regimen had some activity, the toxicity precluded further evaluation.
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PMID:Phase II trial of vinorelbine plus doxorubicin in relapsed small-cell lung cancer: CALGB 9332. 1475 28