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)

A 75 year-old man developed gait disturbance and somnolence over a period of three months. Electroencephalography indicated theta slowing and cerebrospinal fluid (CSF) examination showed an increased cell count of 23/microliter and IgG of 7.2 mg/dl. He showed fatigue-inducing muscle weakness and the Harvey-Masland test demonstrated a low M-wave amplitude of 0.6 mV which increased to 3 mV with 50 Hz high-frequency stimulations. The serum titer of P/Q type anti-voltage-gated calcium channel (VGCC) antibody was quite high at 11,901 pmol/L (< 20 pmol/L). The patient was diagnosed as Lambert-Eaton myasthenia syndrome (LEMS) although at first no carcinoma was detected. Immunoadsorption therapy with a phenilalanine absorber column resulted in a reduction in the titer of anti-VGCC antibody to half of the initial concentration, but it increased again within several days. Six repeats of immunoadsorption and concomitant administration of prednisolone at a dose of 40 mg daily succeeded in reducing the anti-VGCC antibody titer of to below 390 pmol/L. The patient's consciousness disturbance and muscle weakness improved simultaneously over the next month and the lumbar puncture and electroencephalography showed normal results. Prednisolone administration was maintained at a dose of 30 mg daily and one year after occurrence of the first symptoms, a small cell lung carcinoma was detected. There was no evidence of limbic encephalitis such as an elevation of anti-Hu antibody in his CSF and serum or abnormal signal intensities in the hippocampal formations on MR imaging. The etiology of his disturbed consciousness remained unclear, but, in the case of LEMS, it could be a manifestation of a paraneoplastic syndrome associated with small-cell lung carcinoma. It is noteworthy that the anti-VGCC antibody titer rose to 1,262 pmol/L 2 months before his tumor was detected and decreased to 286 pmol/L after chemotherapy. P/Q type anti-VGCC antibody could therefore be a useful tumor marker reflecting activity of small-cell carcinoma.
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PMID:[Response to immunoadsorption and steroid therapies in a patient with carcinomatous Lambert-Eaton myasthenia syndrome accompanied by disturbed consciousness]. 1100 28

This study examined the association between the most important prognostic factors in non-small cell lung carcinoma (NSCLC) and self-reported pretreatment quality of life (QoL) and the impact of the presence, severity and changes in respiratory symptoms on general symptoms and QoL. The study included 262 patients. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-LC13 were used to assess symptoms and QoL before radiotherapy. Patients with inoperable NSCLC showed major differences in self-reported QoL as a function of clinical prognostic factors. A significant association was found between World Health Organization (WHO) performance status and QoL but not other prognostic factors. Dyspnoea was the only respiratory symptom associated significantly with general symptoms, physical and psychosocial functioning and QoL. Furthermore, changes in dyspnoea were associated significantly with changes in physical and role functioning, global QoL and fatigue as assessed 6 weeks after radiotherapy. These results indicate that palliation of dyspnoea may have a significant beneficial effect on QoL and that palliation of other respiratory symptoms is not necessarily associated with improvement of general symptoms, physical and psychological functioning or global QoL.
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PMID:Pretreatment quality of life of inoperable non-small cell lung cancer patients referred for primary radiotherapy. 1120 2

Best Supportive Care (BSC) is the treatment of choice when cure is not achievable with anticancer treatments and involves management of disease-related symptoms. In the palliative treatment of non-small cell lung cancer (NSCLC) radiation therapy has for a long time been the cornerstone of symptom management, although the best schedule is still to be defined. Chemotherapy, on the other hand, has been excluded from classical definitions of BSC and has been reserved only for selected patient populations in which a survival benefit was demonstrated using cisplatin-based regimens. We reviewed randomized trials on both palliative radiotherapy and chemotherapy in order to assess the impact of anticancer treatments on quality of life in advanced NSCLC patients. While no randomized trials compared radiation therapy with a control arm not including it, several randomized trials assessed the use of different schedules. Hypofractionated schedules seem to have comparable palliative activity when compared with the standard fractionated regimens, at least in metastatic, poor-prognosis patients. In locally advanced, inoperable NSCLC higher radiation doses administered with conventional fractionation achieve better results in terms of local control and survival. The rate of palliation of local symptoms is high, being 60-80% for chest pain and hemoptysis, while breathlessness and cough are controlled at a somewhat lower rate (50-70%). General symptoms (fatigue, anorexia, and depression) are affected in a minority of patients. Chemotherapy was compared with BSC in several randomized trials, in some of which an analysis of the quality of life was included. Results are consistent in favor of its palliative role and, when local symptom control is assessed, rates of palliation seem similar to those achieved by radiation. Benefits apply to metastatic NSCLC patients with good performance status, low body weight loss, age below 70-75. However, some studies support the use of chemotherapy also in patients with poor prognostic features. A comparison in terms of quality of life and symptom palliation between different chemotherapy regimens is the object of few trials. Both chemotherapy and radiation have an important role in the palliative treatment of advanced NSCLC patients and should be included in BSC programs. Future randomized trials should assess the best way of combining these two approaches.
Lung Cancer 2001 Jun
PMID:Best supportive care in non-small cell lung cancer: is there a role for radiotherapy and chemotherapy? 1139 3

This phase I study was designed to determine the maximum tolerated dose (MTD) and toxicity of a weekly docetaxel (TXT) and cisplatin (CDDP) combination regimen in advanced non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC who were previously untreated were eligible. Docetaxel, at a starting dose of 20 mg m(-2) per week on days 1, 8 and 15, was combined with a fixed dose of cisplatin 80 mg m(-2) on day 1. Docetaxel was increased in 5 mg m(-2) per week steps. Chemotherapy was given in a 4-weeks cycle. Dose-limiting toxicities (DLTs) were defined as grade 3-4 leukopenia, thrombocytopenia, anemia, fever with grade 4 neutropenia and more than grade 2 non-hematologic toxicity, with the exception of nausea, vomiting, and alopecia. Omission of chemotherapy on day 8 and/or 15 was also considered DLT. Eighteen patients were enrolled in this study. Leukopenia, anemia and fatigue were the DLTs. No grade 4 toxicities were seen in any patients. The overall response rate was 44.4% (95% confidence interval, 21.5-67.4%). The recommended dose of TXT to be combined with CDDP 80 mg m(-2) on day 1 is 35 mg m(-2) per week on days 1, 8 and 15. This is a promising regimen, therefore a multicenter phase II study is now under way.
Lung Cancer 2001 Jul
PMID:A phase I study of weekly docetaxel and cisplatin in advanced non-small cell lung cancer. 1142 97

Randomized phase III studies reported this year prove that docetaxel is superior both to best supportive care (BSC) and to a standard regimen of vinorelbine or ifosfamide as second-line therapy for advanced non--small cell lung cancer. In a landmark study authored by Dr Frances Shepherd, 204 patients with stage IIIB/IV non--small cell lung cancer who had failed previous cisplatin-based chemotherapy were randomized to receive either docetaxel (100 mg/m(2) or 75 mg/m(2) every 3 weeks) or BSC. The median survival of patients assigned to docetaxel was 7.6 months, significantly longer than the median of 4.6 months in patients treated with BSC alone. The rate of febrile neutropenia was 22% in patients receiving 100 mg/m(2) docetaxel but only 1.8% when the dose was 75 mg/m(2). Patients treated with docetaxel required less additional opioid analgesia and palliative radiotherapy than those receiving BSC. Patients in the docetaxel 75 mg/m(2) arm also were significantly less likely to lose 10% or more body weight and to experience severe fatigue. In a second phase III study led by Dr Frank Fossella, 373 patients were randomized to docetaxel 100 mg/m(2), docetaxel 75 mg/m(2), or a control arm of vinorelbine 30 mg/m(2) or ifosfamide 2 g/m(2). Median survival was similar between the two groups (range, 5.5 to 5.7 months). However, the survival rate at I year was significantly higher in patients assigned to 75 mg/m(2) than in the control arm. Patients receiving docetaxel 75 mg/m(2) experienced better global quality of life (Lung Cancer Symptom Scale: patient-rated) than patients receiving vinorelbine or ifosfamide. A higher incidence of grade 4 neutropenia and febrile neutropenia was observed in the docetaxel arms of the study, but the incidence of infections was low and nonhematologic toxicities were similar across all treatment arms. These studies show docetaxel provides meaningful survival and clinical benefits in second-line non-small cell lung cancer. The dose recommended in this setting is 75 mg/m(2) every 3 weeks.
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PMID:Review of two phase III randomized trials of single-agent docetaxel in previously treated advanced non--small cell lung cancer. 1144 53

Cisplatin-based chemotherapy improves survival in appropriately selected patients with stage IV non-small cell lung cancer (NSCLC). However, cisplatin-based regimens have well-known dose-related toxicities, particularly renal insufficiency and neurotoxicity. On the basis of prior preclinical and phase I studies, we initiated a phase II study of SPI-77 (STEALTH) Liposomal Cisplatin) in patients with stage IIIB and IV NSCLC who failed previous treatment with platinum. Disease in all subjects had progressed during therapy, failed to respond, or progressed within 3 months after discontinuing the platinum-based chemotherapy. Between January and June 1999, 13 patients were enrolled at our institution. Patient characteristics included: seven women, six men; median age, 61 years; median Karnofsky performance status, 80%; median number of prior chemotherapy regimens, two (range, 1-3). All patients had adequate hepatic and renal function. SPI-77 was administered at a dose of 260 mg/m(2) IV every 3 weeks. A median of two cycles (range 1-6) were given; the total number of cycles was 35. Among the 12 patients evaluable for response, two had (17%) stable disease and ten (83%) had progressive disease. The median survival was 24.3 weeks, and the median follow-up was 43.9 weeks. Toxicity could be evaluated in all subjects. Moderate anemia (46% of cycles, <or=grade 2; 3% of cycles, >or=grade 3) with minimal granulocytopenia and thrombocytopenia (26% of cycles grade 1; 0% of cycles, >or=grade 2) were the most notable manifestations of myelosuppression. Grade 3 nonhematological toxicities included dyspnea (8%), fatigue (8%), and pain (8%). There were no grade 4 toxicities. These data suggest that this liposomal cisplatin formulation does not have appreciable activity in this population of patients with NSCLC who had received prior platinum-based chemotherapy. The lack of encouraging results from SPI-77 use in other phase I and II studies resulted in early closure of this trial by the manufacturer.
Lung Cancer 2001 Dec
PMID:A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer. 1171 40

Irinotecan (CPT-11) and cisplatin (P) are both active agents against non-small cell lung cancer (NSCLC), and their combination has shown in vitro an additive or synergistic effect. We conducted a phase II study to determine the toxicity and efficacy of their combination as salvage treatment in patients with advanced NSCLC progressing after a docetaxel-based front line regimen. Forty-four patients with histologically confirmed NSCLC were enrolled. The patients' median age was 60.5 years; 39 patients (87%) were male; 38 (86%) had stage IV disease; and 32 (73%) had a performance status (WHO) 0-1. CPT-11 was administered as a 60 min i.v. infusion at a dose of 100 mg/m(2) on day 1 and 110 mg/m(2) on day 8; P was administered at a dose of 80 mg/m(2) on day 8 after CPT-11 administration. Treatment was repeated every 3 weeks. A total of 159 chemotherapy cycles was administered. In an intention-to-treat analysis, nine patients (22; 95% CI: 9.28-34.62%) achieved a partial response (PR), 8 (20%) had stable disease (SD), and 24 (58%) progressive disease (PD). The median duration of response was 4 months, the median time-to-progression (TTP) 8 months, and the median survival for the entire group 8 months. Grade 3-4 neutropenia was observed in 20 (46%) patients and in four cases this was febrile, requiring patient's hospitalisation. Grade 3-4 thrombocytopenia occurred in four (9%) patients. Grade 3-4 diarrhoea was seen in 12 (27%) patients and three of them required hospitalisation. Grade 2-3 neurotoxicity was observed in two (4%) patients and grade 2-3 fatigue in 14 (32%). Other toxicity was mild and no treatment-related death was reported. The combination of CPT-11 and P is a safe, well-tolerated, and active regimen for the treatment of patients with advanced NSCLC previously treated with a docetaxel-based front-line regimen.
Lung Cancer 2001 Dec
PMID:Cisplatin and irinotecan (CPT-11) as second-line treatment in patients with advanced non-small cell lung cancer. 1174 7

Cancer-related causes of anaemia include anaemia of chronic disorders, infections, autoimmune haemolysis associated with malignant conditions, bone marrow invasion by the tumour or clonogenic marrow dysfunction, iron, folate, or vitamin B 12 deficiency and bleeding from tumour erosion. Treatment-related anaemia results from chemotherapy, radiotherapy and bone marrow fibrosis. Severe anaemia increases the burden of treatment, contributes to fatigue, reduces the quality of life and may also delay or limit further treatment. Blood transfusion is currently the most common form of treatment and patients rarely require transfusion unless the haemoglobin is less than 8 g/l. It is often difficult to predict which patients will develop anaemia and require treatment, but the proportion of patients receiving transfusions increases markedly if the pre-treatment haemoglobin concentration is below 10 g/dl. Four studies have systematically evaluated the effects of erythropoietin on anaemia in lung cancer patients and each of these trials is likely to contribute information concerning the clinical benefit of erythropoietin in treating or preventing treatment-related or disease-related anaemia. Most of the improvements in quality of life observed with erythropoietin administration occurred with haemoglobin levels between 10 and 12 g/dl, and not with levels between 7 and 10 g/dl, with a plateau effect above 12 g/dl. Consequently, a 'functional' level of haemoglobin that appears to be more important is 12 g/dl, because it may be favourably associated with a significant improvement in fatigue compared with lower haemoglobin levels. This 'functional' level would be in keeping with the body's physiological erythropoietin response.
Lung Cancer 2001 Dec
PMID:Role of erythropoietin in the treatment of lung cancer associated anaemia. 1174 10

The aim of the present phase II study was to assess the activity and safety of gemcitabine-cisplatin combination in advanced NSCLC, and to evaluate the impact of this regimen in terms of symptom benefit and quality of life (QOL). Eighty patients with pathologically confirmed advanced (stage IIIB and IV) NSCLC were enrolled into this study. Gemcitabine was administered on days 1, 8 and 15 at a dose of 1000 mg/m(2), and cisplatin was given on day 2 at a dose of 100 mg/m(2). The cycles were repeated every 4 weeks. The impact of treatment on QOL and on tumor-related symptoms was evaluated with the validated EORTC forms (QLQ-C30 and LC-13). The regimen was relatively well tolerated. Myelosuppresion was the principal toxicity. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 58, 65 and 30% of patients respectively. In 143 cycles (35%) the administration of gemcitabine on day 15 was omitted due to myelosuppresion. Non-hematological toxicities were generally mild. Among the 76 patients available for response evaluation, there were 5 complete responses (7%) and 26 partial responses (34%); an overall response rate of 41%. The median duration of response was 8.0 months. The median survival for all 80 patients was 11.0 months and the actuarial 1-year survival probability 45%. During therapy global QOL improved in 22% of patients and particular functional domains increased in 19-37% of patients. Dyspnea was released in 36% of patients, fatigue in 45%, chest pain in 38%, shoulder pain in 27%, cough in 44%, and hemoptysis in 75%. The mean intensity scores of the last three symptoms decreased significantly with therapy. Our study confirmed relatively high efficacy of the gemcitabine-cisplatin combination in patients with advanced NSCLC. Of particular importance was that treatment with gemcitabine-cisplatin combination in a large proportion of patients was also associated with remarkable symptomatic release and with improvement of QOL. However, the high frequency of myelotoxicity-related gemcitabine omissions on day 15 of the cycle indicates that modification of the schedule should be considered in standard care.
Lung Cancer 2002 Jan
PMID:A phase II study of gemcitabine plus cisplatin in patients with advanced non-small cell lung cancer: clinical outcomes and quality of life. 1175 Jul 16

Although 60% of those diagnosed with non-small-cell lung cancer are 60 years of age or older, the elderly are often undertreated. Furthermore, those older than age 70 are under-represented in clinical research trials. Tremendous bias exists against treating the elderly; therapeutic nihilism and constrained societal/financial resources conspire to maintain the status quo. In limited stage small cell carcinoma of the lung (SCLC), a pivotal meta-analysis by Pignon et al. showed no obvious benefit for chemoradiation over chemotherapy alone in patients older than 70 years of age. However, more recent trials have revealed a clear-cut benefit for fit elderly patients to receive combined modality therapy versus chemotherapy alone, even though outcome generally remains superior for younger patients. For patients with locally advanced non-small-cell lung cancer, conflicting results exist. Individual trials evaluating combined modality therapy have shown no impairment in survival for older patients, but retrospective analyses of the Radiation Therapy Oncology Group database have demonstrated that increased therapeutic intensity does not translate into improved outcome compared with standard, single daily fraction radiation alone. Weighted survival analyses that deduct time spent with progressive disease or significant toxicity have reinforced this notion. In advanced non-small-cell lung cancer, fit elderly patients who receive platinum-based regimens do as well, or nearly as well, as patients younger than age 70, although the incidence of neutropenia and fatigue is often higher. Platinum doses above 75 mg/m2 every 3 weeks to 4 weeks are relatively more toxic in the elderly than are lower doses. Three separate studies from Italy have formally assessed the elderly. One showed superiority for single-agent vinorelbine versus best supportive care regarding survival rates and quality of life. A second showed a marked survival advantage for combination vinorelbine and gemcitabine versus vinorelbine alone. However, a much larger, more credible study demonstrated no benefit for combination vinorelbine and gemcitabine versus the constituent single agents. To date, no elderly-specific trials have addressed the role of taxanes or of platinum-based combination therapy versus non-platinum monotherapy or doublets. Comprehensive evaluation of comorbidities and their influence on outcome have not been conducted, and there are virtually no data for patients older than age 80.
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PMID:Elderly patients with lung cancer: biases and evidence. 1205 91


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