Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gallium nitrate is a group IIIa metal that was found to be active in animal species. Gallium nitrate exerts its antitumor effects via a transferrin binding mechanism. This agent is of interest in small cell lung cancer since 26 of 27 small cell carcinoma cell lines tested had increased levels of transferrin receptors. In a phase I study using a continuous infusion, the dose limiting toxicity was nausea when gallium nitrate was given at doses of 400 mg/m2/day. Other effects included elevations of serum creatinine, hypocalcemia, hypomagnesemia, decreased hearing and paresthesias. Activity has been seen in pretreated patients with malignant lymphoma, bladder carcinoma and small numbers of patients with small cell lung carcinoma. To determine the activity of continuous infusion gallium nitrate, this phase II trial was undertaken in patients with small cell lung cancer previously treated with chemotherapy.
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PMID:Phase II trial of gallium nitrate in previously treated patients with small cell lung cancer. 839 97

This study sought to determine the principal toxicities and feasibility of administering paclitaxel as a 3-hour infusion followed by carboplatin without and with granulocyte colony-stimulating factor (G-CSF) in chemotherapy-naive patients with stage IV non-small cell lung carcinoma (NSCLC), and to recommend doses for subsequent clinical trials. Twenty-three patients were treated with paclitaxel at doses ranging from 175 to 225 mg/m2 followed by carboplatin targeting area under the concentration-time curve (AUC) 7 or 9 mg/mL.min every 3 weeks. AUCs were targeted using the Calvert formula with estimated creatinine clearance as a surrogate for the glomerular filtration rate. A high rate of intolerable, mutually exclusive toxicities, consisting primarily of thrombocytopenia, as well as neutropenia, nausea and vomiting, and mucositis, precluded escalation of carboplatin above a targeted AUC of 7 mg/mL.min with paclitaxel 225 mg/m2, which approaches the maximum tolerated dose (MTD) of paclitaxel given as a single agent on a 3-hour schedule. Moderate to severe peripheral neurotoxicity occurred in several patients after multiple courses. Due to the heterogeneous nature of the principal toxicities and the ability to administer clinically-relevant doses of both agents in combination without G-CSF, further dose escalation using G-CSF was not performed. Nine of 23 (39%) total patients and 43% of 21 assessable patients had partial responses (PR). The recommended doses for subsequent clinical trials are paclitaxel 225 mg/m2 as a 3-hour infusion followed by carboplatin at a targeted AUC of 7 mg/mL.min. The ability to administer clinically-relevant single agent doses of paclitaxel and carboplatin in combination, as well as the significant antitumor activity noted in this phase I trial, indicate that further evaluations of this regimen in both advanced and early stage NSCLC are warranted.
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PMID:Phase I study of paclitaxel on a 3-hour schedule followed by carboplatin in untreated patients with stage IV non-small cell lung cancer. 922 Feb 92

In mice, 4-nitrobenzylidene malononitrile (AG1714), which belongs to the tyrphostin family, reduced toxicity induced by doxorubicin and cisplatin without impairing their antitumor efficacy. AG1714 reduced mortality induced by doxorubicin and cisplatin. It prevented, in a dose-dependent manner, cisplatin-induced nephrotoxicity as assessed by measurement of serum creatinine and blood urea nitrogen levels. The protective effect of AG1714 was most pronounced on its administration 2 h before cisplatin. AG1714 also prevented doxorubicin-induced myelosuppression as assessed by the scoring of bone marrow nucleated cells and colony-forming units. Cisplatin-induced small intestinal injury was also protected by AG1714 as assessed by histopathological analysis. In vitro, AG1714 reduced cisplatin-induced apoptosis in a murine fibroblastic cell line (A9) and did not affect doxorubicin-induced apoptosis of B-16 melanoma cells. In contrast to its protective effect against mortality and injury of normal tissues induced by chemotherapy, AG1714 did not impair its antitumor activity and in some tumor models enhanced it. This was evident by using the murine tumors B-16 melanoma, Lewis lung carcinoma, and methylcholanthrene-induced fibrosarcoma and the human tumors SK-28 melanoma and human ovary carcinoma xenografts in nude mice. Experiments in which low and high doses of cisplatin and doxorubicin were administered to tumor-bearing mice demonstrated that AG1714 reduced mortality of high-dose chemotherapy and increased its therapeutic index. AG1714 could provide a novel, useful tool to improve chemotherapy by allowing dose intensification.
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PMID:Tyrphostin 4-nitrobenzylidene malononitrile reduces chemotherapy toxicity without impairing efficacy. 962 80

The primary aim of this phase II study was to determine the response rate of a combination of paclitaxel and carboplatin in advanced non-small cell lung cancer (NSCLC) in a multicentre setting. The secondary aim was to determine time to progression (TTP), 1-year survival rate and toxicity. 65 patients were treated and all of them were included in the follow up for survival and toxicity. 60 patients were followed for response rate and time to progression. 55% were stage IV patients and 45% stage IIIB patients. The treatment consisted of paclitaxel 200 mg/m2 given as a 1-h i.v. infusion and carboplatin given as a 30 min i.v. infusion and the latter was dosed by using the Calvert formula at an area under the concentration time curve (AUC) of 5. The glomerular filtration rate (GFR) was determined by iohexol clearance and was not calculated from the serum creatinine level. The chemotherapy courses were given every third week with a maximum number of six or eight courses for patients who responded late. As premedication we used 8 mg betamethasone 40 min prior to infusion and then 10 min later clemastin and cimetidine. One complete response and 18 partial responses were seen giving a response rate of 29%. 40% of the patients progressed during the treatment and 28% had stable disease. The median TTP was 22 weeks. At a minimum follow up of 1 year, the 1-year survival rate was 38% and the median survival rate was 41 weeks. Haematological toxicity was mild with no grade 4 leucopenia and only seven patients (11%) had grade 3 leucopenia. There was no grade 4 toxicity. Grade 3 toxicity was seen as myalgia 5%, allergic reaction 3% and peripheral neuropathy 6%. 15% of the patients had a dose reduction due to neurotoxicity. The haematological toxicity was much milder than we expected, probably because of more exact determination of the GFR. This trial confirms the results of earlier reported trials of the efficacy and the ease of the regimen as an out-patient treatment option in advanced NSCLC. The main problem with this treatment is peripheral neuropathy.
Lung Cancer 1999 May
PMID:Treatment with paclitaxel 1-h infusion and carboplatin of patients with advanced non-small-cell lung cancer: a phase II multicentre trial. Joint Lung Cancer Study Group. 1044 61

Because high circulating levels of glucocorticoids impair immunity and predispose to infections, we evaluated whether indices of cortisol (F) production could predict infections in patients with Cushing syndrome (CS) caused by ectopic production of ACTH (EA). Charts of 54 consecutive patients with untreated EA, without underlying diagnosis of small cell carcinoma of the lung, were reviewed, and types of infections, white blood cell (WBC) count, fever, as well as the glucocorticoid indices [0800 h F, daily urine F excretion (UFC), and daily urine 17-hydroxysteroid/g creatinine excretion (17OHS)], were recorded. Thirty-five patients had no or clinically mild infection; the remaining 19 patients had severe, systemic infection (n = 13) and/or sepsis (n = 6), including either bacterial or opportunistic pathogens or both (73.7%, 42.1%, and 13.8%, respectively). The latter group of patients had significantly higher indices of hypercortisolism (F, UFC, and 17OHS) than those with mild or no infections, but these indices did not correlate with temperature or WBC count. Thresholds for identifying severe infection were selected for maximal positive predictive value and were: F, 43.1 microg/dL; UFC, 2000 microg/day; and 17OHS, 35 mg/g creatinine. The most accurate discriminator for severe infection was 17OHS, based on a positive predictive value of 64.7%. Our data strongly suggests that the likelihood for a bacterial or opportunistic infection in CS patients, even without underlying small cell carcinoma of the lung, is greatest in patients with extreme hypercortisolism. The predictive value of total WBC count or the presence of an elevated temperature is not sufficient to identify patients with severe, life-threatening infection.
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PMID:Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin. 1115 75

A 73-year-old man was admitted to our hospital with productive cough and dyspnea. His chest X-ray and CT scan showed a mass lesion on the lower lung field, pleural effusion on the left side, metastatic lesion in the right lung, and multiple metastases in the liver. The diagnosis was non-small cell carcinoma of the lung. Unfortunately, he had suffered from chronic nephritis; his creatinine level was 2.1, and his creatinine clearance was 29 ml/min. He received 4 courses of combined chemotherapy of carboplatin (AUC 5, day 1) and weekly paclitaxel (60 mg/ m2, day 1, 8, 15) every 4 weeks. His subjective symptoms as side effects were mild except for accidental melena due to colon diverticulum. Almost all lesions identified at admission were regressed by the chemotherapy. Although renal dysfunction often prevents patients with lung cancer from receiving systemic chemotherapies, in this case the combined chemotherapy of carboplatin and weekly paclitaxel proved to be a relatively safe and effective therapy for those patients with renal dysfunction.
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PMID:[A case of non-small cell lung carcinoma successfully treated with carboplatin and weekly paclitaxel under renal dysfunction]. 1557 Sep 41

To face the problem of organ shortage, marginal grafts from 36 donors which had been refused for single transplantation were used for double-kidney transplantation (D-KTX). The residual kidney function was evaluated by the Muenster double kidney score. In a 5-year period kidneys from 57 marginal donors were transferred to our center. According to the Muenster double kidney score, the kidneys were distributed to single, double or refusal of transplantation. Sixteen male and 20 female donors were used for D-KTX (70+/-9.3 years, range 53-86). Thirty-six recipients (23 male, 13 female; 60.5+/-6.9 years) were double-grafted within a mean cold ischemic time of 19.3+/-3.4 h. Immunosuppression varied according to human leukocyte antigen (HLA)-mismatch. Graft and patient survival was observed up to 5 years. Initial graft function rate was 69%. Two recipients had a primary nonfunction (5.5%) and nine recipients suffered from delayed graft function (DGF; 25%). One-, 2-, 3-year creatinine values were 1.6 +/- 0.5, 1.9 +/- 0.6 and 2.2 +/- 0.7 mg/dl, respectively. One-, 2-, 3-, 4- and 5-year function rate was 93.7%, 93.5%, 81.8%, 76.4% and 55%, respectively (n = 32, 31, 22, 17 and 9). Acute rejection rate was 19%. 4 grafts were lost to chronic rejection (months 22, 25, 28, 48). Six (16%) died in long-term follow-up because of pneumonia (n = 2), carcinoma of the lung (n = 1), cardial complications (n = 2) and multiorgan failure (n = 1). D-KTX is a safe way to face the problem of organ shortage. However, a score for preoperative evaluation of marginal kidneys for single, dual or refusal of transplantation is essential.
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PMID:Long-term follow-up of double kidney transplantation using a score for evaluation of marginal donors*. 1577 66

Small cell lung cancer is highly sensitive to chemotherapy, and a survival advantage with its use is well established. However, whether chemotherapy also confers such benefits to patients with severe organ dysfunction has not been extensively studied. The goal of this study was to provide further guidance for clinical decision-making. Medical records from small cell lung cancer patients who were seen at a single tertiary care institution between 1994 and 2002 were reviewed. All patients with severe organ dysfunction were identified. The latter was defined as creatinine >/=3mg/dl, total bilirubin>/=3mg/dl, and/or platelet count</=50 x10(6) per milliliter. An in depth review of treatment and outcome in this patient subgroup was then undertaken. A total of 993 small cell lung cancer patients were seen during this period, and 25 (2.5%) had severe organ dysfunction. Eleven had been treated with chemotherapy, 11 had not, and this information was not retrievable in 3. Cyclophosphamide, etoposide (oral or intravenous), paclitaxel, cisplatin, or carboplatin were prescribed as single agents or in combination; 8 of 11 patients received an initial dose reduction. With chemotherapy, three patients normalized their bilirubin, and one manifested a notable drop. Median survival was 150 days for chemotherapy-treated patients but only 10 days for those who did not receive it. One patient died a few days after chemotherapy; three others were hospitalized immediately thereafter; and two were lost to follow up. In five patients, no notable adverse events were noted in the medical record. These preliminary findings suggest that, even in the presence of severe organ dysfunction, a subgroup of small cell lung cancer patients can tolerate chemotherapy, normalize their laboratory parameters, and go on to live for several months.
Lung Cancer 2005 Aug
PMID:Ramifications of severe organ dysfunction in newly diagnosed patients with small cell lung cancer: contemporary experience from a single institution. 1602 15

A 56-year-old woman, with dysgeusia in which nearly all food was felt as sweet, was admitted to our hospital seeking for treatment. Serum sodium concentration was 113 mmol/L, but serum creatinine, zinc, urea nitrogen, and potassium, as well as blood glucose, were all within normal ranges. Dysgeusia disappeared when serum sodium level was normalized, but recurred when hyponatremia relapsed. She was diagnosed as having large cell lung carcinoma. We considered that the cause of hyponatremia was inappropriate secretion of antidiuretic hormone (SIADH) due to lung carcinoma. Miraculin is one of taste-modifying substances which fits the sweet receptor site and induces a strong sweet taste. We considered that taste-modifying substances same as miraclin are involved in the pathophysiology of this disease.
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PMID:[Sweetness dysgeusia in a case of SIADH caused by lung carcinoma]. 1698 5

A dendritic cell (DC) vaccine strategy has been developed as a new cancer immunotherapy, but the goal of complete tumor eradication has not yet been achieved. We have previously shown that baculoviruses potently infect DCs and induce antitumor immunity against hepatomas in a mouse model. Baculovirus-infected, bone marrow-derived DCs (BMDCs) display increased surface expression of costimulatory molecules, such as CD80, CD86 and major histocompatibility complex (MHC) classes I and II, and secrete interferons and other proinflammatory cytokines. In this study, we evaluated the induction of antitumor immunity in mice by baculovirus-infected BMDCs against lung cancer and melanoma. After treatment with baculovirus-infected BMDCs, murine lung tumors caused by Lewis lung carcinoma (LLC) cells were significantly reduced in size, and the survival of the mice was improved. In addition, experiments using a melanoma mouse model showed that baculovirus-infected BMDCs inhibited tumor growth and improved survival compared with controls. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine levels remained normal in baculovirus-infected BMDC-treated mice. Our findings show that baculovirus-infected DCs induce antitumor immunity and pave the way for the use of this technique as an effective tool for DC immunotherapy against malignancies.
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PMID:Induction of antitumor immunity against mouse carcinoma by baculovirus-infected dendritic cells. 2087 26


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