Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Cisplatin was reported to be an effective radiation sensitizing agent. The effect was also reported to depend on dose intensity. But the incidence of complication was demonstrated in the relationship with the dose escalation curve of anti-cancer agent. The major side effect of CDDP was occasionally serious, as in renal toxicity or bone marrow suppression. W-Platinum is the trial of concurrent chemoradiotherapy. Cisplatin and its derivative, Carboplatin, were selected as effective radiation sensitizing agents and to obtain high-dose intensity and additive cytotoxicities by interaction between the two drugs. Concomitant administration of two platinum anti-cancer agents has the advantage of reduction of side effects compared with administration of single anti-cancer agents to the same degree. The first case was a recurrence of epipharyngeal cancer after 3 courses of chemotherapy, including CDDP or CBDCA. This case was suspected to be cancer-resistant to CDDP. The second case was post-operative residual lung cancer. The pre-operative diagnosis was stage III A. A poor prognosis was expected. This case was disease-free and alive for 1 year after W-Platinum administration. The most frequent complication was bone marrow suppression. Patients were rescued from bone marrow suppression with administration of G-CSF. Renal toxicity could be suppressed with sufficient hydration.
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PMID:[Trial of radiation and cisplatin, carboplatin combination chemotherapy for advanced cancer (W-platinum chemoradiotherapy]. 912 11

Reports are reviewed on G-CSF studies in neutropenia after lung cancer chemotherapy, especially randomized trials including our data. With preventive administration of G-CSF after dose-intensive chemotherapy in small-cell lung cancer, three studies showed that G-CSF shortened the duration of neutropenia, and reduced the incidence of neutropenic fever, the use of antibiotics and hospitalization with statistical significance, but showed no advantage in response rate or the incidence of infection-related death. And the effect on survival has not been proved clearly. When G-CSF was administered to afebrile neutropenic patients, it accelerated recovery from neutropenia significantly, but did not clearly reduce the incidence of neutropenic fever or infection. When G-CSF was administered to febrile neutropenic patients combined with antibiotics concurrently, it also could accelerate recovery of neutropenia significantly, but could not reduce neutropenic fever or infection compared with no CSF. For optimal use, it has not been proved when G-CSF should be started. Marginal therapy is considered to be administration in neutropenia with fever or infection and in severe neutropenia. Investigational therapy is considered for administration in neutropenia without fever or infection and use in clinical trials. Because no standard therapy with G-CSF has been established, additional clinical trials are necessary.
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PMID:[Problems and recommendations for use of G-CSF in lung cancer patients with neutropenia after chemotherapy]. 936 20

We conducted a phase I study of irinotecan (CPT-11) and etoposide (VP-16) given sequentially to untreated patients with metastatic non-small-cell lung cancer. Arm A: CPT-11 was given over 90 min on days 1-3 and VP-16 was given over 60 min on days 4-6. Arm B: VP-16 was given on days 1-3 and CPT-11 on days 4-6. G-CSF was given to all patients daily on days 7-17. Twenty-seven patients were entered randomly at the two arms. The major dose-limiting toxicities in arms A and B were granulocytopenia and diarrhoea. Transient elevations of transaminases and bilirubin were observed in both arms. The degree of the toxicities did not differ between the two arms. The maximum tolerated doses (MTDs) were 60 mg m-2 CPT-11 and 60 mg m-2 VP-16 in both arms. Of the 13 patients who received more than two cycles, two out of five achieved partial response (PR) at the first level of arm A and one out of four achieved PR at the second level of arm B. We conclude that these schedules of sequential CPT-11 and VP-16 administration were inappropriate because of severe toxicities.
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PMID:Phase I study of sequentially administered topoisomerase I inhibitor (irinotecan) and topoisomerase II inhibitor (etoposide) for metastatic non-small-cell lung cancer. 940 Sep 32

Using sIL-2R and IAP values as indices, we examined the effect of administering BRMs to relieve bone marrow suppression and immunosuppression associated with modified VP therapy (CBDCA + VP-16) in patients with lung cancer. G-CSF significantly improved leukopenia. PSK inhibited decreases in the leukocyte count, although the action of PSK was weaker than that of G-CSF. It was shown that there was no relapse or that the course after relapse was slow, in patients showing gradual changes in sIL-2R and IAP values or showing low sIL-2R and IAP levels. Serum sIL-2R levels provide a useful indicators for continuing chemotherapy and evaluating the patient's status. In addition, evaluating a combination of sIL-2R levels and IAP levels allows the prediction of the course of the disease after relapse, and it was suggested that BRMs administration was also useful for maintaining the effects of chemotherapy.
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PMID:Changes in serum soluble IL-2 receptors (sIL-2R) and immunosuppressive acidic protein (IAP) associated with chemotherapy for lung cancer. 942 81

A human lung cancer xenograft, LC-GP, producing granulocyte-colony stimulating factor and parathyroid hormone-related protein was established by transplantation into severe combined immunodeficient (SCID) mice. The lung cancer patient and SCID mice bearing LC-GP showed leukocytosis and hypercalcemia. G-CSF and PTHrP gene expression were demonstrated in the primary lung cancer, metastatic lesions and LC-GP xenograft. Immunohistochemical analysis confirmed the presence of G-CSF protein in LC-GP xenograft cells. LC-GP possessed activated c-Ki-ras oncogene (point mutation at codon 12). This LC-GP lacked apparent G-CSF receptor expression. The expression of G-CSF and PTHrP may be coregulated by the activated c-Ki-ras oncogene, and autocrine stimulation of G-CSF is unlikely.
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PMID:A human lung cancer xenograft producing granulocyte-colony stimulating factor and parathyroid hormone-related protein. 946 57

The present state and the problems of G and GM-CSF in cancer chemotherapy, especially for solid tumors in Japan, were reviewed. One of the problems is that adaptation is restricted to several tumors, and the other that recommended doses are about half or one-fourth as much as in North America or Europe. With G-CSF after dose-intensive chemotherapy in small-cell lung cancer, three studies showed G-CSF shortened the duration of neutropenia, and reduced the incidence of neutropenic fever, use of antibiotics and hospitalization, while they showed no advantages in terms of response rate and the incidence of infection-related death. Moreover, the effect on survival has not been proved. In afebrile neutropenic patients, G-CSF could accelerate recovery from neutropenia, but did not reduce the incidence of neutropenic fever. In febrile neutropenic patients with antibiotics, it could also accelerate recovery from neutropenia, but did not reduce neutropenic fever compared with no CSF except in some subsets. Our retrospective study showed the effects of G-CSF in grade 4 neutropenia were comparable with grade 3 neutropenia. The functions of neutrophils with G-CSF after chemotherapy were reported to be increased or maintained. Clinical benefits were only obtained in certain dose-intensive chemotherapy or in limited subsets. Additional clinical trials and a guideline like ASCO's should be planned.
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PMID:[Cytokines in cancer chemotherapy: present state and problems in use of G- and GM-CSF for solid tumors in Japan]. 947 24

Circulating myeloid (CFU-GM) and erythroid (BFU-E) progenitor levels were evaluated weekly throughout 3 courses of treatment with vinorelbine (VNB) ifosfamide (IFO) and filgrastim (G-CSF) with or without addition of cisplatin (DDP) in 20 stage IIIB or IV non small-cell lung cancer patients. In IFO, VNB, DDP-treated patients, BFU-E mobilization in peripheral blood following chemotherapy and G-CSF was completely lacking, in contrast with the patients treated with IFO, VNB plus G-CSF. CFU-GM release, however, was of the same order in the 2 groups of patients. Further investigations are needed to explain why presence of DDP in this chemotherapeutic protocol hinders erythroid progenitor release in peripheral blood.
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PMID:Cisplatin inhibits erythroid committed progenitor (BFU-E) mobilization in peripheral blood. 968 95

The prognostic significance of neutropenic fever in lung cancer patients receiving chemotherapy with or without radiotherapy was investigated. Male patients and patients with squamous cell lung cancer had a higher incidence of febrile episodes than female patients and patients with other cell types, but the differences were not significant. Patients with a poor performance status had a significantly higher incidence of febrile episodes. An indwelling central venous catheter was an important risk factor for febrile episodes, indicating that bacteremia was one of the major causes of fever. The median survival time of the patients who developed febrile episodes during chemotherapy was significantly shorter than that of patients without fever (6.1 vs 12.0 months), whether or not cases of early death within 3 months were excluded (8.9 vs 13.1 months). The prevention of infectious complications during anticancer treatment by the use of rh G-CSF and the early initiation of antimicrobial chemotherapy, although the results are inconclusive, may be worthwhile.
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PMID:Prognostic significance of febrile episodes in lung cancer patients receiving chemotherapy. 969 9


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