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

Twenty patients with locally advanced or metastatic non-small cell lung cancer entered a study of recombinant human methionyl G-CSF (r-metHuG-CSF) as an adjunct to ifosfamide, cisplatin and etoposide (IPE) regimen. Chemotherapy consisted of three courses of cisplatin 25 mg/m2, ifosfamide 1.5 g/m2 (with uroprotection) and etoposide 100 mg/m2 given on days 1-4 of a 21-day cycle. r-metHuG-CSF, 5 micrograms/kg, was administered subcutaneously from day 5 to day 14. Eighteen out of 20 patients completed the three courses (57 evaluable cycles). Grade 3-4 neutropenia affected 50, 42 and 22% of the patients during cycles 1, 2 and 3, respectively, whereas thrombocytopenia was observed in 25% of the patients throughout the chemotherapy protocol. Haematological toxic events requiring transfusions and/or antibiotics were responsible for 11 unplanned hospitalizations. Among these only three were exclusively devoted to febrile neutropenia care, the remaining eight being mainly required for blood transfusions. There were no deaths during the study duration. Dose reductions were needed in 65% of the patients and chemotherapy was delayed by thrombocytopenia in five patients. The total relative dose intensity was 84%. Eleven (55%) patients responded (one complete and 10 partial responses). Median survival was 9.5 months. We concluded that IPE combination chemotherapy can be administered safely with the support of r-metHuG-CSF inasmuch as neutropenia appears as mild to moderate and manageable. Optimal delivery of chemotherapy is still limited by other toxicities, mainly thrombocytopenia, but the successful relative dose intensity observed herein deserves further studies designed to analyze a dose intensity-survival relationship in non-small cell lung cancer.
Lung Cancer 1996 Jun
PMID:r-metHuG-CSF support to ifosfamide, cisplatin, etoposide chemotherapy in non-small cell lung cancer. 879 15

From June 1991 to August 1994, 61 patients with stage III unresectable non-small-cell lung cancer (NSCLC; 16 cases of stage IIIA with N2 bulky disease and 45 cases of stage IIIB) were treated with ifosfamide given i.v. at 3 g/m2 on day 1, carboplatin given i.v. at 200 mg/m2 on days 1 and 2, etoposide given i.v. at 120 mg/m2 on days 1-3 (ICE) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) given s.c. at 5 micrograms/kg on days 4-13. Chemotherapy was given every 3 weeks for up to three cycles and, unless the disease progressed, was followed by thoracic radiotherapy on the tumor volume (total dose 60 Gy) and mediastinum (40 Gy). All patients had measurable or evaluable unresectable disease and a performance status (Eastern Cooperative Oncology Group) of 0-1. Only 61% of the enrolled patients received the full program of chemoradiotherapy according to the study design. At the end of sequential chemo-radiotherapeutic treatment, 41% of the patients had an objective response (24 partial responses and 1 complete response), 31% showed no change and 28% had progressive disease. The response rate noted for patients in stage IIIA with N2 bulky disease and that recorded for patients in stage IIIB did not differ significantly. The median time to progression was 5.4 months and the median survival was 8.2 months, with the 1-year survival rate being 31%. Sites of progression were mostly intrathoracic. Haematological toxicity was the main side effect, with grade III-IV thrombocytopenia being reported in 24% of the 165 courses of intensive ICE chemotherapy given. Febrile neutropenia was described in six courses (three patients). Non-haematological toxicities and radiotherapy-related side effects were generally mild and easily manageable. In conclusion, in unresectable stage III NSCLC a short program of moderately intensified ICE chemotherapy with rhG-CSF protection followed by sequential radiotherapy failed to increase the percentage of objective responses and reached a median survival comparable with that previously achieved with standard doses.
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PMID:Phase II study of intensive chemotherapy with carboplatin, ifosfamide and etoposide plus recombinant human granulocyte colony-stimulating factor and sequential radiotherapy in locally advanced, unresectable non-small-cell lung cancer. 882 99

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is effective in countering chemotherapy-induced neutropenia. However, serum rhG-CSF levels cannot be maintained throughout the course of rhG-CSF therapy. The drop in serum rhG-CSF levels may vary with the duration of rhG-CSF administration or with the circulating neutrophil counts. We investigated the relationship between serum G-CSF levels and circulating neutrophil counts and the pharmacokinetics of rhG-CSF for patients with lung cancer who had been treated with myelosuppressive chemotherapy and then with subcutaneous rhG-CSF (lenograstim, 2 micrograms per kg of body weight per day). Twelve patients were randomly assigned to four groups with different rhG-CSF therapy schedules. Serum G-CSF levels were measured by an enzyme immunoassay method. Serum G-CSF levels during the rhG-CSF therapy greatly exceeded endogenous G-CSF levels and were mainly due to the presence of exogenous rhG-CSF rather than increased levels of endogenous G-CSF. Despite the duration of rhG-CSF administration, serum G-CSF levels during rhG-CSF therapy were inversely correlated with circulating neutrophil counts (r2 = 0.73, P < 0.0001). The value for the area under the concentration-time curve of rhG-CSF on the day of neutrophilia was lower than that on the day of neutropenia (P < 0.05). Our results suggest that the fall in serum G-CSF levels during rhG-CSF therapy may result from increased clearance and/or decreased absorption of rhG-CSF, two processes related to circulating neutrophil counts.
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PMID:Levels of recombinant human granulocyte colony-stimulating factor in serum are inversely correlated with circulating neutrophil counts. 884 65

Hematopoietic growth factors (HGF) such as G-CSF and GM-CSF stimulate cell growth of the bone marrow and thereby mitigate the myelotoxic effect of chemotherapy. Using 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) for therapy response monitoring of patients with small-cell lung cancer, both an extension and an intensification of thoracic bone marrow uptake were noted in patients treated with HGF (n = 5) compared to those patients without HGF supplementation (n = 11). FDG uptake was a very sensitive marker of stimulated hematopoiesis, and both the extension and the intensification of uptake have to be noted during HGF therapy.
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PMID:Bone marrow uptake of fluorine-18-fluorodeoxyglucose following treatment with hematopoietic growth factors: initial evaluation. 894 Jul 29

We report a therapy-related MDS (RAEB) patient with eosinophilia, unbalanced translocation der(7)t(1;7) (q12;q22) and lung cancer. We observed no increase in cytokine levels in serum or in the conditioned medium (CM) of peripheral T cells cultured with or without IL-2. When bone marrow (BM) cells were cultured with GM-CSF, IL-3 and SCF in a semisolid system, the colonies were exclusively eosinophilic. Cytogenetic analysis of the colony cells identified the same chromosome abnormality in all metaphases to that of BM cells. Suspension and clonogenic colony assay of BM cells cultured with various cytokines showed predominant eosinophilic growth and differentiation with GM-CSF, but not with the other cytokines examined. These findings, together with mild morphological abnormalities of eosinophils, indicate clonal involvement of eosinophils in the myelodysplastic syndrome (MDS) clone, and that the eosinophilia was derived from the neoplastic clone with the translocation and was not associated with the patient's lung cancer.
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PMID:Clonal involvement of eosinophils in therapy-related myelodysplastic syndrome with eosinophilia, translocation t(1;7) and lung cancer. 898 50

Sixty-three patients with extensive-stage small-cell lung cancer were randomized to receive either cyclophosphamide, vincristine, doxorubicin and etoposide (CODE) alone or CODE plus recombinant human granulocyte colony-stimulating factor (rhG-CSF). rhG-CSF administration in support of CODE chemotherapy resulted in increased mean total received dose intensity for all drugs (P = 0.03) with a significant improvement in survival (P = 0.004).
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PMID:CODE chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer. 901 43

Increased local production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by genetically modified tumor cells can induce specific antitumor cellular immunity. We constructed a recombinant adenovirus expressing murine GM-CSF and tested it for therapeutic efficacy in a syngeneic murine lung cancer model system. In vitro transduction of Lewis lung carcinoma cells with adenovirus-mGM-CSF suppressed tumor formation in syngenic mice (C57BL/6), and transduced and irradiated Lewis lung carcinoma cells induced regression of pre-established wild-type tumors without in vitro selection for transductants. Low, but significant, levels of specific antitumor cytotoxic T lymphocytes (CTL) were observed in mice inoculated with GM-CSF but not with reporter virus-transduced tumor cells. GM-CSF-transduced cells induced the accumulation of dendritic cells at the site of tumor, consistent with a mechanism involving improved tumor antigen presentation. These data suggest that transduction of tumor cells with recombinant GM-CSF adenovirus may be an effective and practical cancer gene therapeutic strategy.
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PMID:Genetic immunotherapy of established tumors with adenovirus-murine granulocyte-macrophage colony-stimulating factor. 901 22

The maximum tolerated dose (MTD) of etoposide and carboplatin without growth factor support was previously defined by Cancer and Leukemia Group B (CALGB) as 200 and 125 mg/m2/day x 3, respectively, given every 28 days to previously untreated patients who have extensive, small-cell lung cancer (SCLC). Myelosuppression was dose-limiting. The purpose of this phase I trial was to determine if granulocyte macrophage colony-stimulating factor (GM-CSF) support allows the dosage of the combination of etoposide and carboplatin to be increased above the previously determined MTD. In this CALGB study of 44 evaluable patients with performance status 0-2, cohorts were treated with etoposide and carboplatin given intravenously on days 1-3 followed by GM-CSF (molgramostim) given subcutaneously on days 4-18. Four dose levels of bacteria-derived recombinant GM-CSF (5, 10, 20 microg/kg/day and 5 microg/kg every 12 h), three dose levels of etoposide (200, 250, and 300 mg/m2/day x 3), and two dose levels of carboplatin (125 and 150 mg/m2/day x 3) were evaluated. There was no chemotherapy dose escalation in individual patients. With 5 microg/kg/d GM-CSF, the first etoposide and carboplatin cycle of 300 and 150 mg/m2/day x 3, respectively, could be administered with acceptable toxicity. However, GM-CSF did not allow repeated administration of this dose-escalated regimen every 21 days, since delayed platelet and/or neutrophil recovery was dose limiting in later cycles. These results demonstrate that GM-CSF alone has limited capability to support the repeated administration of high doses of etoposide and carboplatin. CALGB currently is testing the ability of interleukin (IL)-6 given with GM-CSF to ameliorate the cumulative myelosuppression of this intense regimen.
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PMID:Phase I trial of etoposide, carboplatin, and GM-CSF in extensive small-cell lung cancer: a Cancer and Leukemia Group B study (CALGB 8832). 902 Feb 83

Autonomous or continuous granulocyte colony-stimulating factor. (G-CSF)-production in malignant neoplasms is considered to induce leukocytosis without apparent infection. We examined G-CSF gene expression in human non-small cell lung cancer (NSCLC) and discussed its clinicopathological significance. Northern blot analysis revealed G-CSF gene expression in 14 of 84 surgical specimens (16.7%, 10/30 squamous cell carcinoma, 3/50 adenocarcinoma, 1/4 large cell carcinoma). Eight patients (57.1%, 8/14) with NSCLC showing G-CSF gene-expression had peripheral blood leukocytosis (> 8,000/microliter). The prognosis was significantly worse in 10 stage I or II NSCLC showing G-CSF gene expression (p < 0.01, Cox-Mantel test). These findings suggest that G-CSF gene expression is common event in the early stage of primary NSCLC, while it cannot completely explain the leukocytosis induced by lung cancer.
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PMID:Gene expression of granulocyte colony stimulating factor (G-CSF) in non-small cell lung cancer. 906 82

The importance of the dose intensity of chemotherapy in achieving maximal therapeutic effect has recently been reported for several chemosensitive malignant diseases, with Murray et al. reporting that intensive weekly chemotherapy using the cisplatin, vincristine, doxorubicin, and etoposide (CODE) regimen in small-cell lung cancer (SCLC) is very effective. However, leukopenia is the major obstacle to delivering the planned dose in intensive regimens. Therefore, we investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) could allow full drug doses to be given as scheduled, thereby improving the final outcome. Extensive-stage (ES) SCLC patients were randomized to receive either CODE alone or CODE with rhG-CSF, with the CODE regimen consisting of cisplatin given i.v. at 25 mg/m2 weekly for 9 weeks; vincristine given i.v. at 1 mg/m2 during weeks 1, 2, 4, 6, and 8; and doxorubicin given i.v. at 40 mg/m2 and etoposide given i.v. at 80 mg/m2 for 3 days during weeks 1, 3, 5, 7, and 9, rhG-CSF at 50 micrograms/m2 was given s.c. on the days on which cytotoxic drugs were not given. From May 1989 to September 1991; 64 patients were enrolled in the study, of whom 63 were analyzable (31 for CODE alone and 32 for CODE with rhG-CSF). No difference in any of the patients' characteristics except gender was found between the two groups. The complete response (CR) rate was 34% in the CODE with rhG-CSF group and 23% in the CODE alone group; the median survival was 59 and 32 weeks, respectively, in these groups (P = 0.004). Therefore CODE with rhG-CSF improved the survival of ES SCLC patients. On the basis of these results a phase III study to determine whether CODE with rhG-CSF would increase survival as compared to the standard regimen in ES SCLC was designed by the Japan Clinical Oncology Group.
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PMID:Dose-intensive chemotherapy in extensive-stage small-cell lung cancer. 927 38


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