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)

The efficacy of combined high-dose etoposide with standard dose cisplatin was evaluated in patients who had refractory lung cancer after standard chemotherapy. Each patient was given etoposide at 500 mg/m2/day on day 1 to 3 continuously (total dose 1,500 mg/m2) and cisplatin at 80 mg/m2 on day 1. Fifteen patients (7 adenocarcinoma, 5 small cell lung cancer, 2 squamous cell lung cancer and 1 sarcoma, which latter was difficult to distinguish from giant cell carcinoma) were entered in this study. The overall response was 41.7% (5 of 12); five partial response, 6 no change, and 1 progressive disease. Three treatment-related deaths were observed; one resulted from sepsis and two from respiratory failure because of tumor progression. All of the patients developed severe myelosuppression; the mean nadir white blood cell count was 400, and the mean nadir platelet count was 24,000 in 28 evaluable courses. The range of maximum concentration of etoposide determined by HPLC was from 17.4 to 39.1 micrograms/ml. These results suggest that high-dose etoposide combined with a standard dose of cisplatin is effective against refractory lung cancer.
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PMID:[Pilot phase II trial of high-dose etoposide combined with cisplatin in the treatment of refractory lung cancer]. 131 97

Forty-four patients with previously untreated histologically proven small cell lung cancer (SCLC) were treated with a combination of teniposide 60 mg/m2 intravenously (IV) on days 1 through 5 and carboplatin 400 mg/m2 IV on day 1 every 28 days for six courses. Patients with limited disease (LD) subsequently received prophylactic cranial and thoracic radiotherapy. Of the 44 patients, 40 were evaluable for response: 31 (78%) achieved an objective response; 9 of 18 patients (50%) with LD had a complete response (CR), with a partial response (PR) plus CR rate of 78%. Two of 22 patients (9%) with extensive disease achieved a CR, with a combined PR and CR rate of 77%. Median duration of response for all evaluable patients was 253 days (36 weeks). Median duration of survival for LD patients was 368 days (52 weeks). Survival of LD patients was 86% at 6 months, 52% at 12 months, and 26% at 18 months. Median duration of survival for all patients in the study was 275 days, with a survival of 79% at 6 months, 36% at 1 year, and 12% at 18 months. Myelosuppression was the main toxicity, with World Health Organization (WHO) grade 3 or 4 infection occurring in 38% of patients. However, no patient died of sepsis or hemorrhage. Treatment was otherwise well tolerated, with no neurotoxicity or nephrotoxicity documented. The high activity of this drug combination justifies its use as first-line treatment of previously untreated SCLC.
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PMID:Teniposide (VM-26) and carboplatin as initial therapy for small cell lung cancer. 132 28

The incidence and risk of septic complications in 382 patients treated for small cell lung cancer with combination chemotherapy at a single centre have been analysed. Full protocol doses were employed throughout with no dose reduction after episodes of severe or life-threatening sepsis (SLTS). 50 (13%) patients experienced 66 episodes of SLTS associated with 1978 cycles of chemotherapy (3.2% cycles affected). 20 (5.2%) patients died due to sepsis (SD) of whom only 4 had experienced SLTS with a previous cycle of treatment. The others died as a result of their first septic episode. A model comprising four variables, age (< or = 50 or > 50 years), Karnofsky performance status (KP < or = 50 or > 50), treatment (two- or three-drug regimen) and previous sepsis (SLTS or no SLTS with previous cycles) was found to satisfactorily describe the incidence of SLTS and SD in the study population and once validated in another patient groups this model should allow identification of high-risk individuals before treatment starts. If so, we propose that high-risk patients (age > 50 years, KP < or = 50, treatment with three-drug regimen) receive 50% of protocol doses in the first cycle of treatment with escalation to 75% and eventually 100% doses in subsequent cycles if sepsis does not supervene. Those with one or two risk factors present run a relatively low risk of SLTS or SD and we consider that full-dose chemotherapy should be used throughout in these individuals.
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PMID:Predicting septic complications of chemotherapy: an analysis of 382 patients treated for small cell lung cancer without dose reduction after major sepsis. 133 39

The combination of etoposide and cisplatin has become one of the standard treatments for small cell lung cancer. Ifosfamide, an analogue of cyclophosphamide, has demonstrated single-agent antitumor activity comparable with that of the most active agents used to treat small cell lung cancer. Because ifosfamide is relatively nonmyelosuppressive and its principal dose-limiting toxicity, urotoxicity, has largely been eliminated with the introduction of the uroprotective agent mesna, we undertook a phase II study of the combination of all three agents (etoposide/ifosfamide/cisplatin) in good-performance-status, extensive-disease patients 70 years of age or younger. Twenty-five patients (17 men and eight women; median age, 58 years) were treated with 75 mg/m2 etoposide, 20 mg/m2 cisplatin, and 1.0 g/m2/d ifosfamide administered intravenously for 5 days. Mesna (200 mg/m2) was given as a bolus prior to the first day of chemotherapy and then daily by continuous infusion (900 mg/m2 over 24 hours) between administrations of chemotherapy. Mesna was continued for 12 hours after the last dose of ifosfamide. Treatment cycles were planned every 4 weeks for four cycles. Due to severe toxicities in the first eight patients, subsequent patients received only 4 days of treatment (20% dose reduction). Of the 25 extensive-disease patients studied, 23 are evaluable for response. Seven (30%) achieved a complete response and 10 (43%) had a partial response (overall response rate, 73%). Five patients (22%) had stable disease (< 50% decrease and no evidence of disease progression for at least 4 weeks), and disease progressed in 1 patient (4%). The median survival time was 42 weeks (range, 2 to 160+ weeks). Granulocytopenia was dose-limiting: median granulocyte count was 0.486 x 10(9)/L, 21% of cycles had a granulocyte nadir below 0.2 x 10(9)/L, and four patients died of sepsis. Three patients required platelet transfusion and nine needed blood transfusion. Microscopic hematuria occurred in eight patients (11% of treatment cycles) but was reversible in all cases. A number of central nervous system symptoms were reported but could not be definitely attributed to ifosfamide/mesna. Gastrointestinal toxicity was generally mild, which is attributed to the use of an aggressive antiemetic program. The etoposide/ifosfamide/cisplatin regimen is active and produced a complete response rate of 30% in extensive small cell lung cancer; the duration of response and survival appears similar to that of other standard regimens. The 5-day schedule produced excessive toxicity in this patient population, necessitating a 20% dose reduction (by using a 4-day schedule). The method of administration required a minimum of 5 hospital days per cycle.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A phase II study of ifosfamide in combination with etoposide and cisplatin in the treatment of extensive small cell lung cancer. 133 22

The synergism of combined high-dose etoposide with standard dose cisplatin (HD-EP) was evaluated in 20 patients who had relapsed after treatment of small cell lung cancer. Each patient was given etoposide at 500 mg/m2/day on days 1 to 3 and cisplatin at 80 mg/m2 (two patients given 120 mg/m2) on day 1; autologous bone marrow was not transplanted. Five patients were given recombinant human granulocyte colony-stimulating factor (rhG-CSF, 50 micrograms/m2) in an attempt to reduce HD-EP induced neutropenia. The overall response was 50% (9 of 18); one complete response (6%), eight partial responses (44%), seven no change (39%), and two progressions of disease (11%). Of the 18 evaluable patients, 12 had been treated with regimens of conventional doses of etoposide with conventional doses of cisplatin or carboplatin, and of these, five (42%) achieved a partial response. The median duration of response was 8.4 weeks (range, 5.3 to 17.7) and the median survival time was 20.3 weeks (range, 1.6 to 91). All of the patients developed severe myelosuppression; rhG-CSF did not shorten the period of the leukopenia. Mucositis and liver dysfunction were the major nonhematologic manifestations of toxicity. Two treatment-related deaths resulted from sepsis. These results suggest that the activities of high doses etoposide with standard doses of cisplatin are synergistic against small cell lung cancer.
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PMID:Evaluation of high-dose etoposide combined with cisplatin for treating relapsed small cell lung cancer. 169 57

The relation between degree of myelosuppression and episodes of infection was analyzed in 36 patients (92 treatment courses) with small cell lung cancer (SCLC) treated with intensive chemotherapy. The two regimens used were cisplatin (CDDP) + adriamycin (ADR) + cyclophosphamide (CPA) + etoposide (VP-16) + granulocyte-colony stimulating factor (G-CSF) and CDDP + teniposide (VM-26) + G-CSF, and they induced grade 3 or 4 leukopenia in 88% of treatment courses and febrile episodes in 60%. In the febrile courses, the mean nadirs of leukocyte and neutrophils (820 +/- 581/mm3, 101 +/- 267/mm3) were significantly longer (P less than 0.01) and the mean durations of grade 3 and 4 leukopenia and neutropenia significantly longer (P less than 0.001) than those of the non-febrile courses. It was noted, however, that febrile episodes appeared frequently in courses having the nadir of leukocytes below 1,000/mm3 (80%) or the nadir of neutrophils below 100/mm3 (74%). The administration of antibiotics was required for about 7 days to patients with febrile episodes. Sepsis was experienced in five courses, in which the neutrophils were all zero. All the patients, however, could be managed by an administration of antibiotics immediately after a febrile episode appeared, without delaying the subsequent chemotherapy except for one patient, who had had a performance status (PS) of 3 prior to chemotherapy.
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PMID:The frequency and management of infectious episodes and sepsis in small cell lung cancer patients receiving intensive chemotherapy with granulocyte-colony stimulating factor. 172 56

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)] received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m-2 in 60 courses, 300 mg m-2 in 69, 330 mg m-2 in 236 and 350 mg m-2 in 11, with 120 mg m-2 etoposide on days 1, 3 and 5 and either 40 mg m-2 adriamycin or 60 mg m-2 epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m-2. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m-2 carboplatin had a neutropenia below 200 microliters-1 and a thrombopenia below 100,000 microliters-1. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carboplatin in association with etoposide and either adriamycin or epirubicin for untreated small cell lung cancer: a dose escalation study of carboplatin. UCL Clinical Oncology Group. 255 61

One hundred and twelve patients with small cell lung cancer (SCLC) were treated with a combination (CAVE) of cisplatin (60 mg/m2 day 1), adriamycin (45 mg/m2 day 1), etoposide (80 mg/m2 days 1-2-3) and cyclophosphamide (1 g/m2 day 1) given every 4 weeks. A total of 10 courses were given. Response evaluation was initially evaluated after the first two courses of CAVE and repeated at least after treatment completion. This regimen was associated with severe hematological toxicity, mainly leucopenia; five toxic deaths related to sepsis were observed. One hundred and one patients were evaluable for response: 63 with limited disease and 49 with extensive disease. Overall complete and partial response rates after the first two courses of chemotherapy were 16% and 63% respectively but 14 late complete responses were documented, leading to a 30% total complete response rate; 38% in patients with limited disease and 19% in those with disseminated disease. Median overall survival was 46 weeks with a 17% 2 year survival. The only significant prognostic factor for survival was the type of response. There was no survival difference between 'early' and 'late' complete responders. Complete responders had a 75 week median survival time with a 34% 2 year survival. CAVE is thus an effective regimen for SCLC, but with a considerable toxicity.
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PMID:Phase II study of an intensive combination chemotherapy with cisplatin, adriamycin, etoposide and cyclophosphamide (CAVE) in small cell lung cancer. 283 89

High-dose etoposide (1.0-1.5 g/m2) was given to 17 small cell lung cancer (SCLC) patients with metastases in the central nervous system. In 4 out of 9 evaluable patients with brain metastases and 4 out of 5 patients with meningeal carcinomatosis a response was seen. In all patients severe myelosuppression was observed. Three patients died of septicemia during the aplastic phase. Despite severe toxicity high-dose etoposide is potentially useful for CNS metastases of SCLC.
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PMID:High-dose etoposide for central nervous system metastases of small cell lung cancer. Preliminary results. 303 52

A three-drug regimen composed of adriamycin, 50 mg/m2 and cyclophosphamide, 500 mg/m2 administered on day 1; and VP-16-213, 50 mg/m2 days 1-5, with courses repeated at 3-week intervals, was studied in 24 consecutive patients with extensive-stage small cell lung cancer (SCLC). Twelve of 33 patients (36%) evaluable for toxicity developed life-threatening marrow suppression and 12% died of septicemia following the first course of treatment. Eleven of 24 patients (46%) with extensive disease achieved an objective response and only one was classified as a complete response. Survival was related to performance status and metastatic site but was not influenced by tumor response. The present study is distinctive from that of previous reports of the same or similar three-drug regimen in that the response rate is lower and toxicity is substantial. Nonetheless, survival as measured by median duration (7.9 months) and proportion alive at 1 year (35%) is comparable to that of previous reports.
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PMID:Adriamycin, cyclophosphamide, and etoposide (VP-16-213) in extensive-stage small cell lung cancer. 609 53


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