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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung cancer is biologically and clinically classified as non-small-cell lung cancer (NSCLC) or small cell lung cancer (SCLC). NSCLC is accounting for about 80% of lung cancers. Serum tumour markers may be helpful in diagnostic of this cancer and in monitoring of the tumour growth or tumour volume reduction. Recent studies have focused on a new family of markers--hematopoietic cytokines, defined also hematopoietic growth factors (HGFs). It has been shown that the actions of HGFs are not limited to hematopoietic cells but can also affect the proliferation of nonhematopoietic cells. Some clinical investigations have shown cell surface receptors for macrophage--colony stimulating factor (M-CSF) in cancer cells and autologous production of M-CSF in various human cell lines derived from cancer. The purpose of this investigation was to compare serum levels of M-CSF in NSCLC patients to a control group, to assess pre- and post treatment levels of M-CSF in relation to levels of commonly accepted tumour markers such as carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA 21-1), and to define the diagnostic sensitivity of G-CSF in NSCLC. In this study, the serum levels of tumour markers were measured in 34 patients with NSCLC and in 20 healthy subjects. Serum samples were drawn before surgery and 10, 30, 90, 180 and 270 days after surgery. M-CSF and CEA were assayed using ELISA system and CYFRA 21-1 was measured by radioimmunoassay (RIA). The serum level of M-CSF was significantly increased in cancer patients relative to the control group on the 10th day after operation. Concentrations of CYFRA 21-1 were decreased on the 10th day, CEA on the 30th day and M-CSF on the 90th day after surgery. The diagnostic sensitivity of M-CSF was 55%, CEA--62% and CYFRA 21-1-51%. The diagnostic sensitivity and the serum level of M-CSF were related to the stage of NSCLC. These results suggest that M-CSF may be useful in diagnostic and monitoring of NSCLC, but it needs further studies.
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PMID:[Macrophage-colony stimulating factor (M-csf) in diagnostic and monitoring of non-small-cell lung cancer (NSCLC)]. 1168 Feb 64

The purpose of this study is to determine whether it is feasible to administer high-dose epirubicin (135 mg m(-2)) combined with a fixed dose of cisplatin every 2 weeks with G-CSF support in patients with metastatic non-small-cell lung cancer (NSCLC). Subsequently, the efficacy of the recommended dose of this regimen was tested in a phase II study in patients with relapsed NSCLC. In the initial feasibility study at least 6 patients were entered at each of the 4 dose levels tested. A fixed dose of cisplatin 60 mg m(-2) was given. Epirubicin was administered at 120 mg m(-2) on dose level 1, 135 mg m(-2) on dose level 2 and 3 and 135 mg m(-2) on dose level 4. Patients treated at dose level 3 and 4 received G-CSF support on days 3-12. Cycles were repeated every 3 weeks on the first 3 dose levels and every 2 weeks on the fourth dose level. A total of 27 patients were then treated on dose level 4, which appeared to be feasible in the initial study. In the initial study, a total of 86 courses were administered. Haematological toxicity was the principal side effect. None of the patients encountered dose-limiting toxicity in the first course, which confirmed that epirubicin 135 mg m(-2) could be combined with cisplatin 60 mg m(-2) and accelerated by G-CSF support to a 14-day-schedule. In the subsequent phase II study with this schedule, 89 courses were administered. The relative dose intensity of cisplatin and epirubicin was 0.90 and 0.91, respectively. Myelosuppression was frequent with 70% and 63% of patients experiencing WHO grade III or IV leukocytopenia and thrombocytopenia, respectively. 6 cases of febrile neutropenia were observed, with 2 treatment-related deaths. Non-haematological toxicity consisted mainly of nausea and vomiting, which was grade III in 22% of patients. Renal toxicity grade I and II occurred in 37% and 4% of patients, respectively. 55% of these patients had received prior cisplatin-containing chemotherapy. On an intention-to-treat basis 9 partial responses were recorded in 27 patients (33%; 95% confidence interval, 15%-51%). Accelerated cisplatin and high-dose epirubicin with G-CSF support is a feasible and promising regimen in relapsed NSCLC. Myelosuppression limits the use of this regimen in the second-line setting to a selected group of patients with a good performance status. Since the activity of this regimen is encouraging, it is probably best studied in untreated patients.
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PMID:Accelerated cisplatin and high-dose epirubicin with G-CSF support in patients with relapsed non-small-cell lung cancer: feasibility and efficacy. 1172 Apr 28

To evaluate the efficacy and toxicity of weekly docetaxel (D) as II line treatment in non-small cell lung cancer (NSCLC), in November 1999, we started a phase II study on advanced (stages IIIB-IV) NSCLC patients pre-treated with at least one platinum-based chemotherapy regimen with or without radiotherapy. The schedule consisted of D 40 mg/m(2), weekly for 6 weeks, followed by a rest period of 2 weeks, for three cycles or until progression. Eligibility criteria were: histopathologic diagnosis of NSCLC; age <or=75 years; evaluable or measurable progressive lesions; PS (ECOG) 0-2; adequate haematology and biochemistry parameters; no serious concurrent diseases; no symptomatic brain lesions; and informed consent. The end points were assessment of overall response rate, toxicity and quality of life (QoL). Patients were re-evaluated at the end of every cycle. An interim analysis of 18 patients (16 M) was performed. Weekly courses were 132; 16 of 18 patients were evaluable for response and 17 of 18 for toxicity. Two of the 16 patients (12.5%) had a partial response (95% CI: 10.5-14.7%). Haematological toxicity was very mild: grade 1-2 neutropenia occurred in four patients, grade 3 neutropenia in two patients; grade 1-2 anaemia in four patients; and grade 1-2 thrombocytopenia in two patients. Non-haematological toxicity was also very mild, with the exclusion of asthenia (grade 1-2 in ten patients and grade 3 in five patients) and alopecia (grade 1-2 in seven patients and grade 3 in eight patients). No cases of grade 4 toxicity were observed. No QoL evaluations were reported in this interim analysis. In conclusion, these preliminary data confirm that weekly D results in tolerable toxicity in pre-treated NSCLC. Myelo-suppression, the dose-limiting toxicity of every 3 week schedules, is not a clinically relevant problem when D is administered weekly. G-CSF was used only sporadically in four patients, and no febrile neutropenia was reported. Patients were pre-treated with dexamethasone and no allergic reactions were seen. Although the therapeutic activity appears to be comparable to that of every 3 week schedules, more data are necessary before definite conclusions can be drawn. Accrual of patients is still ongoing.
Lung Cancer 2001 Dec
PMID:Weekly docetaxel as II line therapy in non-small cell lung cancer: an interim analysis of a phase II study. 1174

Edatrexate is an antifolate agent with improved in vitro antineoplastic activity as compared with methotrexate. A Mayo phase I trial of edatrexate (E), vinblastine (V), doxorubicin (Adriamycin) (A), cisplatin (C), and filgrastim (GCSF), (EVAC-GCSF) showed promising antineoplastic activity in non-small-cell lung cancer (NSCLC) (Colon-Otero G, et al. Cancer J Sci Am 1997;3:297-302) leading to a phase II trial of this regimen, the results of which are reported here. A total of 34 patients with stage IIIB or IV measurable or evaluable NSCLC were entered in this North Central Cancer Treatment Group phase II study. Treatment consisted of edatrexate 100 mg/m2 intravenously on day 1 and cisplatin 30 mg/m2/d on day 1 and day 2 followed by vinblastine 3 mg/m2 intravenously and doxorubicin 30 mg/m2 intravenously on day 2. Filgrastim was given at 300 microg subcutaneously daily from day 4 to day 18 or until an absolute neutrophil count of 2,000/mm3 or more was obtained. Cycles were repeated every 21 days until either progression or the development of intolerable toxicity. Sixteen of 34 evaluable patients responded to therapy, for a response rate of 47.1% with a 95% CI of 30.3% to 63.8%. Median time to disease progression was 132 days, median survival time was 219 days, and the estimated 1-year survival was 41.2% (95% CI of 27.6-61.5%). The EVAC/G-CSF regimen has significant antineoplastic activity as seen by the response rates for patients with NSCLC. However, this study had significant myelosuppressive toxicity; 56% patients had grade III or higher leukopenia with three treatment-related deaths observed. In addition, Quality of Life assessments indicate that patients experienced an overall decline in quality of life during the course of treatment. These mitigating factors need to be considered regarding further evaluation of this regimen in this patient population.
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PMID:A phase II trial of edatrexate, vinblastine, adriamycin, cisplastin, and filgrastim (EVAC/G-CSF) in patients with non-small-cell carcinoma of the lungs: a North Central Cancer Treatment Group Trial. 1180 52

Intensive chemotherapy combined with chest radiation may ameliorate survival in small cell lung cancer (SCLC). In a prospective study, we treated 18 patients with limited SCLC with an intensive sequential single agent (ifosfamide, carboplatin, etoposide and paclitaxel, (ICE-T)) chemotherapy with the support of unprocessed stem-cell enriched whole blood and G-CSF and concomitant bi-fractionated chest radiotherapy (60 Gy). The treatment was delivered in a short time of 10 weeks. The results were compared with an historical patient group treated with six cycles of standard chemotherapy of etoposide and cisplatin and concomitant chest radiotherapy. After a 3-year median follow up, the 2-year progression free (PFS) and overall survival (OS) are 54 and 63% in the ICE-T group, respectively. In the control group, median PFS and OS were 13 and 17 months and the 2-year PFS and OS were 32% (P=0.20) and 47% (P=0.25), respectively. This short and intensive chemo-radiotherapy regimen is well tolerated and induces promising survival results. The use of stem cell enriched whole blood should be investigated in larger randomized studies.
Lung Cancer 2002 Jun
PMID:Intensive chemotherapy with whole blood stem-cell support and concurrent chest radiotherapy in small cell lung cancer: a phase I/II trial. 1200 45

Pyrazoloacridine (PZA, NSC366140, PD115934) is an acridine derivative currently undergoing clinical evaluation. In preclinical testing, PZA has shown selectivity for solid tumor cell lines, activity in hypoxic, noncycling, and multidrug-resistant cell lines, and synergy with cisplatin in a variety of lung cancer cell lines. In early phase I clinical studies PZA has shown modest activity in ovarian, cervical, and colon cancer. The purpose of the present study was threefold: to determine the maximally tolerated doses of the combination of PZA (3-h infusion) and cisplatin administered with and without Filgrastim (G-CSF) (Amgen, Thousand Oaks, CA) every 3 weeks in untreated or minimally pretreated patients, to describe and quantify the clinical toxicities of combination chemotherapy with PZA and cisplatin, and to evaluate the effects of drug sequencing on the toxicity profile and pharmacologic behavior of PZA. The starting doses in this dose-escalation trial were PZA 400 mg/m2 as a 3-h intravenous infusion and cisplatin 50 mg/m2 as a 1 mg/min intravenous infusion. The sequence of drugs was alternated with each successive course in each patient treated. Twenty-one patients with refractory solid tumors received 43 courses of therapy through four dose levels. Neutropenia was dose-limiting and defined the maximum tolerated dose of PZA 400 mg/m2 and cisplatin 50 mg/m2 without G-CSF support. With G-CSF support, nausea and vomiting were dose-limiting. The maximum tolerated and recommended doses for further study of this combination are PZA 600 mg/m2 over 3 h and cisplatin 50 mg/m2 followed by G-CSF support. Pharmacokinetic analysis showed that sequence does not impact on the pharmacokinetics of PZA when given in combination with cisplatin.
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PMID:A phase I and pharmacologic study of pyrazoloacridine and cisplatin in patients with advanced cancer. 1279 32

The major dose-limiting toxicity associated with myelosuppressive chemotherapy is neutropenia, which can be ameliorated with proactive administration of granulocyte colony-stimulating factor (G-CSF). Pegfilgrastim is a long-acting G-CSF, recently approved by the Food and Drug Administration. The efficacy and safety of pegfilgrastim administered once/chemotherapy cycle have been evaluated in clinical trials involving patients treated with myelosuppressive chemotherapy for breast cancer, lung cancer, non-Hodgkin's lymphoma, and Hodgkin's disease. Two pivotal phase III trials in patients with breast cancer showed that pegfilgrastim is as effective as filgrastim regarding the primary efficacy end point, which was duration of grade 4 (severe) neutropenia in cycle 1 of myelosuppressive chemotherapy. Secondary end points were the frequency of fever with neutropenia (febrile neutropenia), duration of neutropenia in cycles 2-4, depth of the absolute neutrophil count (ANC) nadir, and time to ANC recovery in cycles 1-4. Once/cycle pegfilgrastim 100 microg/kg or 6 mg was as safe and effective as daily filgrastim 5 microg/kg in reducing the frequency and duration of severe neutropenia. A trend toward a greater reduction in the overall frequency of febrile neutropenia with pegfilgrastim was observed. The availability of pegfilgrastim simplifies the use of prophylactic G-CSF, with the potential to increase patient convenience and adherence in management of chemotherapy-induced neutropenia.
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PMID:Safety and efficacy of pegfilgrastim in patients receiving myelosuppressive chemotherapy. 1292 Dec 18

Chemotherapy is now an acceptable treatment for selected patients with non-small-cell lung cancer. With the wide assortment of cytotoxic and supportive-care drugs, there are opportunities for assessing the value of various treatment approaches. This study was undertaken to assess variations in treatment patterns in a large oncology group with emphasis on costs incurred and survival. A total of 1215 patients seen in 1996 by Medical Oncologists (a community-based private practice) were identified as new lung cancer patients by review of billing data. Of these, 858 received chemotherapy and were evaluated for charges. Three hundred were evaluated for charges, hospice care, and survival. Differences in practice patterns for physicians and the causes of those differences were assessed. Differences in survival, charges, and hospice care for those patients who were seen by high-charge and low-charge physicians were measured. Clear differences emerged in practice patterns for these Medical Oncologists. Higher charges were associated with higher average number of chemotherapy cycles given, greater use of second- and third-line chemotherapy and greater use of support drugs, particularly G-CSF and erythropoietin. For stage IV non-small-cell lung cancer, there was no difference in survival or in hospice utilization for the two groups. For all patients combined, there was no significant survival difference. There may be as much as 100% difference in costs incurred for lung cancer chemotherapy based on variations in practice patterns alone without a measurable survival difference. These results suggest approaches for cost-minimization and disease management. These suggestions have been reinforced by recent clinical data and guideline development.
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PMID:Lung cancer: a cost and outcome study based on physician practice patterns. 1522 96

There is much uncertainty whether chemotherapy is beneficial for elderly patients with advanced lung cancer. Whereas age alone is not an adverse prognostic factor, decline of physiological function and comorbidity can result in higher rates of treatment-related toxicity, in particular myelosuppression. The higher incidence of comorbid conditions, frequently sharing the risk profile of the malignancy, can translate into worse survival. Therefore, a geriatric assessment of the patient's overall situation should guide decision-making. Mainstay of treatment of small cell lung cancer (SCLC), also in the elderly, is combination therapy. Several retrospective analyses reveal that in elderly patients often lower drug doses are delivered. However, the treatment outcome of these patients does not appear to be worse compared to younger patients. For functionally independent elderly patients, combination chemotherapy with carboplatin and etoposide, supported by optimized supportive care, possibly including hematopoietic growth factors (G-CSF) to minimize toxicity, should be considered. Special attention to renal function should be given and individualized drug dosing, adapted to the glomerular filtration rate, is mandatory. For patients with some functional dependence or showing a certain degree of comorbidity, preliminary data indicate that single-agent therapy with carboplatin can confer the same benefit as combination chemotherapy, but with reduced toxicity. Single agent oral etoposide, however, seems to be inferior to combination treatment and should not be given routinely in the treatment of this cohort. Further evaluation of these topics is needed, and can be achieved by trials specifically designed for elderly patients or patients with reduced performance status.
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PMID:Chemotherapy in elderly patients with advanced lung cancer. Part I: General aspects and treatment of small cell lung cancer (SCLC). 1559 21

A phase I study of gemcitabine (GEM) and docetaxel (TXT) combination chemotherapy had been performed for unresectable non-small-cell lung cancer, and the dose level of GEM (1,000 mg/m2) on days 1 and 8, and TXT (70 mg/m2) on day 8 every 21 days had been recommended. The combination chemotherapy was repeated> or =2 courses in this phase II study, and the efficacy and safety were evaluated. 31 patients were entered, and the mean number of courses was 3.1. Leukopenia, neutropenia, anemia and fatigue were observed as major adverse reactions. The severe adverse reactions (> or =Grade 3) were leukopenia 48.4% and neutropenia 70.9%. With G-CSF support, all except 2 patients were administered as per schedule, and the TXT dosage in 2 patients was reduced. Other toxicities were mild. The overall response rate was 71.0%, and MST was 515 days. All except the 2 fatal cases on initial hospital admission made the shift to outpatient therapy. These results indicate the efficacy and safety of GEM and TXT combination chemotherapy.
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PMID:[Phase II study of gemcitabine (GEM) and docetaxel (TXT) combination chemotherapy for unresectable non small cell lung cancer]. 1618 23


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