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)

A 67-year-old man was hospitalized with the chief complaint of diffuse abdominal pain for 3 days. Hypercalcemia and acute pancreatitis was found by laboratory examination. Abdominal CT scans showed swelling of the pancreas, multiple liver tumors and osteolytic lesions of bone. Upper mediastinal lobulated mass was suspected from chest x-ray examination, then small cell lung cancer (SCLC) was proved by bronchoscopic and pathological examination. The final diagnosis is SCLC with liver and bone metastasis associated with hypercalcemia and acute pancreatitis. After pancreatitis subsided, the patient was put on chemotherapy. Unfortunately, due to immunocompromise, he died of pneumonia and sepsis. There was no reasonable explanation regarding to the cause of acute pancreatitis except hypercalcemia, which might be due to SCLC with bone metastasis. This is the first report of such a complication in a patient with SCLC.
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PMID:[Small cell lung cancer with liver and bone metastasis associated with hypercalcemia and acute pancreatitis--a case report]. 764 Nov 15

The combination of carboplatin and etoposide is an active and well-tolerated regimen in the treatment of small cell lung cancer (SCLC). The aim of the study was to confirm whether the efficacy could be maintained if etoposide was administered orally. 106 consecutive, unselected, and untreated patients with SCLC (limited disease (LD) 44; extensive disease (ED) 62) were treated with a combination of carboplatin 300 mg/m2 intravenously (i.v.) day 1 and etoposide 240 mg/m2 orally days 1-3 every 4 weeks for six courses or until progression. If oral treatment was inconvenient, i.v. etoposide (120 mg/m2 days 1-3) was allowed. Thoracic irradiation (45 Gy in 22 fractions, split course) was given after three courses of chemotherapy to 29 patients with LD. Objective response (complete and partial) was seen in 89% (confidence interval (CI) 75-97) of patients with LD and in 53% (CI 40-66) with ED. Complete response was seen in 41% (CI 26-57) of patients with LD and in 8% (CI 2-18) with ED. Median time to progression for responders was 11 months and 6 months for patients with LD and ED, respectively. Corresponding median survival was 15 months (range 1-45 months) and 8.5 months (0-26 months). Myelosuppression comprised the main toxicity. Leucopenia (WHO III-IV) was observed in 20% and thrombocytopenia (WHO III-IV) in 16% of the cases. One patient died of sepsis during leucopenia. Oral treatment was convenient for most patients and therapy well tolerated. However, 9 patients (20%; CI 9-36%) with LD and 26 patients (42%; CI 29-56%) with ED received at least part of the etoposide treatment i.v.. The present study shows that the combination of carboplatin and oral etoposide is active and well tolerated, and may be used on an outpatient basis in patients with small cell lung cancer.
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PMID:Is carboplatin and oral etoposide an effective and feasible regimen in patients with small cell lung cancer? 769 81

Thirty-seven extensive disease SCLC patients were treated with ifosfamide 1.0 g/m2 (maximum 1.75 g), VP-16 (etoposide) 75 mg/m2 and cisplatin 20 mg/m2 (VIP) daily for 5 days in hospital. Mesna was given as a continuous infusion until 12 h after the last ifosfamide dose. Treatment was reduced to 4 days after the first 8 patients experienced serious myelotoxicity. 30 patients were evaluable for response. 8 (27%) achieved a complete response and 60% had a partial response. The median duration of response was 23 weeks. The median survival of all 37 patients was 41 weeks, and 47 weeks for the 30 evaluable patients. Fifty per cent and 26% of the evaluable treatment courses were associated with grade 4 and 3 granulocytopenia, respectively. There were eight febrile events including four treatment-related deaths from sepsis on the 5-day regimen. Although the response to VIP was generally rapid, the proportion achieving complete response (27% of evaluable patients) and the median survival is similar to standard chemotherapy regimens which are less toxic and less complex to administer.
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PMID:VP-16, ifosfamide and cisplatin (VIP) for extensive small cell lung cancer. 820 48

Myelosuppression is the major dose-limiting toxicity of chemotherapy in small cell lung cancer (SCLC). The capacity of colony stimulating factors (CSFs) to stimulate granular neutrophil recovery may be of great value to prevent or cure febrile neutropenia and to increase dose-intensity. The aim of this review was to assess the current use of CSFs in SCLC on the basis of experimental and clinical data. Primary CSF administration has been shown to reduce the incidence of febrile neutropenia, hospital admission rate, and antibiotic use subsequent to cyclophosphamidedoxorubicin-high dose etoposide (CDE) chemotherapy, without improvement of survival or disease control. Primary CSF administration may be recommended when the expected incidence of febrile neutropenia is at least 40%. This benefit has not been established with less myelosuppressive regimens, such as cisplatin-etoposide (PE), which remains an alternative combination of SCLC when standard doses are used. A trial comparing high-dose CDE + CSF with PE would be of considerable interest. There is currently little clinical basis for the use of CSFs to increase chemotherapy dose-intensity, outside clinical trials. Peripheral blood progenitor cells mobilized with CSFs offer interesting prospects. Further studies, with later initiation, shorter duration or lower doses of CSFs, are warranted to improve the cost-effectiveness of CSFs. CSF therapy in addition to antibiotics is normally not justified in febrile neutropenia, except perhaps in selected patients with sepsis syndromes, hypotension or pneumonia.
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PMID:Colony-stimulating factors as an adjunct to chemotherapy in small cell lung cancer. 873 24

Small cell lung cancer is a highly chemo-sensitive malignancy. As it often presents with a central lesion, superior vena cava obstruction (SVCO) is not an uncommon manifestation. From January 1990 to December 1993, 161 patients with small cell lung carcinoma were seen at our institution. Twenty (12.4%) of these patients presented with symptoms and signs of SVCO. Initial therapy consisted of radiotherapy in 4 patients and chemotherapy in 16 patients. Of those treated with chemotherapy, patient characteristics included 13 males, median age of 62.5 years (range 51 to 78 years), Eastern Co-operative Oncology Group (ECOG) performance status of 3 to 4 in 7 patients; 1 to 2 in 9 patients, and limited stage disease in 8 patients. The median period of follow-up was 5 months. Nine patients received a combination of cisplatin and etoposide (EP), 5 had cyclophosphamide, doxorubicin and vincristine, 1 had cyclophosphamide, etoposide and vincristine and 1 had monotherapy with oral etoposide. Overall response to chemotherapy was 81% (with 31% complete responses). All responders had resolution of SVCO. Only 3 patients did not respond (1 patient defaulted, 1 patient died of neutropenic sepsis at week one and 1 patient had stable disease). Resolution of SVCO was noted within the first 2 weeks after the first cycle; the earliest being 3 days. The only patient given single-agent oral etoposide responded within 10 days after initiation of treatment. Of the 7 patients with poor performance status (ECOG 3 to 4), 3 died from treatment-related complications. Chemotherapy is highly effective as a primary treatment of small cell lung carcinoma despite presentation with SVCO. However, caution is advised in the use of combination chemotherapy for those presenting with poor performance status. Initial therapy with oral etoposide or radiotherapy should be considered as possible alternatives for these patients.
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PMID:Resolution of superior vena cava obstruction in small cell lung cancer patients treated with chemotherapy. 883 86

Patients with untreated extensive small cell lung cancer (SCLC) with CALGB performance scores 0-2 were treated with etoposide 200 mg/m2/day on days 1-3 and cisplatin doses of 20, 30, or 35 mg/m2/day days 1-3 in a Phase I/II format. Of the nine patients treated at the 35 mg/m2/day cisplatin dose in the Phase I portion of the study, Grade 4 leukopenia occurred in five patients and Grade 4 thrombocytopenia in four. There were two deaths due to myelosuppression and sepsis. This dose was thus considered the maximum tolerated dose (MTD), and a Phase II trial was then conducted using this treatment program. In the Phase II trial of 39 patients, the objective response rate was 67% (95% confidence interval, 50-81%) with 21% complete responses (CI 9-36%). Median survival was 10.5 months. Grade 4-5 leukopenia was seen in 57% and Grade 4-5 thrombocytopenia in 56%. The MTD defined by this Phase I trial represents a 67-100% increase in etoposide and a 32-42% increase in cisplatin dosage compared to prior studies. The observed objective response rates with this regimen are comparable to studies using conventional doses, but hematological toxicity was higher.
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PMID:A phase I/II trial of etoposide and cisplatin in extensive small cell lung cancer: a cancer and leukemia group B study. 888 88

In attempt to develop a new chemotherapeutic regimen including carboplatin (CBDCA), epirubicin (EPI), and VP-16 in extensive small cell lung cancer, with a higher dose intensity compared with previous experience of our group, we determined the maximum tolerated dose (MTD) of VP-16 when administered in association with CBDCA (300 mg/ m2, i.v., day 1) and EPI (75 mg/m2, i.v., day 1), recycling chemotherapy every 3 weeks, with the support of granulocyte-colony-stimulating factor (G-CSF). A total of 15 patients received three dose levels of VP-16 (mg/m2, i.v., daily on days 1-3): 100 (three patients), 120 (six), and 140 (six). G-CSF was administered subcutaneously at the dose of 5 micrograms/kg/day on days 6-15 of each chemotherapy course. The MTD was established at 140 mg/m2 and myelotoxicity, grade 4 neutropenia with death for sepsis in one case and grade 3 thrombocytopenia in three cases, was dose limiting. The recommended dose of VP-16 for a phase II study is 140 mg/m2.
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PMID:Phase I study of chemotherapy with carboplatin, epirubicin, and escalating dose of VP-16 with G-CSF support in extensive small cell lung cancer. 893 78

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

Combined-modality treatment for limited-disease small cell lung cancer using conventional chemotherapy and chest irradiation achieves high response rates, but most patients relapse over a period of 12 to 16 months. To improve current results, we performed a phase II trial including high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT) as part of an early intensification strategy after two cycles of induction therapy. Moreover, to reduce the risk of local recurrence, the protocol included surgical resection in stages I to IIIA patients as well as chest irradiation. Between January 1991 and July 1994, 16 consecutive patients (median age, 50 years; age range, 30 to 59 years) were treated in this single-center trial. The patients received two cycles of conventional chemotherapy consisting of etoposide 500 mg/m2, ifosfamide 4 g/m2, cisplatin 50 mg/m2, and epirubicin 50 mg/m2 plus granulocyte colony-stimulating factor 5 microg/kg at a 3-week interval, followed by PBPC collection and subsequent high-dose etoposide 1,500 mg/m2, ifosfamide 12 g/m2, carboplatin 750 mg/m2, and epirubicin 150 mg/m2 with PBPCT. The duration of the entire chemotherapy program was 9 weeks. Six of 10 patients in stages I to IIIA and one of six patients in stage IIIB received neoadjuvant or adjuvant surgery before high-dose chemotherapy, followed by thoracic (50 Gy) and prophylactic (30 Gy) cranial irradiation. Hematopoietic reconstitution after high-dose chemotherapy occurred within 11 days (range, 9 to 17 days) for both neutrophils (>0.5 x 10(9)/L) and platelets (>20 x 10(9)/L). Oral mucositis (World Health Organization grade 2 to 4) was the predominant nonhematologic toxicity, which was observed in 12 of 16 patients. One patient developed neutropenic septicemia with fatal multiorgan failure. At a median follow-up of 44 months (range, 32 to 77 months) after PBPCT, nine patients are alive and well, resulting in a disease-free and overall survival rate of 56.3% +/- 12.4%. The median overall survival has not yet been achieved. None of the patients who had surgery relapsed or died after therapy. All relapses occurred within the first 12 months after PBPCT. Patients in stages I to IIIA (10 patients) had a 70% +/- 14% overall survival rate at 4 years, while patients in stage IIIB (six patients) had a 33% +/- 19% survival rate at 4 years, with a median survival of 17 months posttransplant. These data demonstrate that a multimodality treatment including early high-dose chemotherapy with PBPCT may lead to a prolonged disease-free survival in the majority of patients. A randomized phase III study has now been initiated to prospectively investigate the role of high-dose chemotherapy, surgery, and chest irradiation in the multidisciplinary approach to limited-disease small cell lung cancer.
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PMID:Multimodality treatment including early high-dose chemotherapy with peripheral blood stem cell transplantation in limited-disease small cell lung cancer. 953 11

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


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