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)

We investigated the possibility of shortening the interval between courses of the commonly prescribed 28-day MVP (mitomycin C, vindesine, and cisplatin) regimen in patients with non-small-cell lung cancer (NSCLC). We conducted a nonrandomized phase II study using recombinant human granulocyte colony-stimulating factor (G-CSF, Chugai) to explore the possibility of shortening the cycle length to 21 days and compared the results with those obtained in historical controls who had received the standard 28-day regimen. A total of 40 patients, 37 of whom were evaluable, were entered in the 21-day treatment group of the trial and were compared with 38 historical controls who had received standard 28-day cycles of MVP at our institution. Patients in the 21-day group received mitomycin C at 8 mg/m2 on day 1, vindesine at 3 mg/m2 on days 1 and 8, and cisplatin at 80 mg/m2 on day 1, with the schedule being repeated every 21 days. Controls had received the same regimen, albeit at 28-day intervals. G-CSF was given s.c. to the patients in the 21-day group at a daily dose of 2 micrograms/kg from day 2 to day 21 of every MVP cycle. The administration of G-CSF to these patients accelerated neutrophil recovery as compared with that observed in the historical controls. Significant differences were found between the two groups in terms of mean neutrophil nadirs (2666/microliters in the first cycle and 1369/microliters in the second for the G-CSF group vs 416/microliters in the first cycle and 685/microliters in the second cycle for the control group; P < 0.0001) and the mean duration of neutropenia (< or = 1000/microliters; 1.0 day in the first cycle and 1.7 days in the second for the G-CSF group vs 8.0 days in the first cycle and 6.9 days in the second for the control group; P < 0.0001). This enabled 32 (86%) of 37 patients in the G-CSF group to complete > or = 2 cycles on schedule. In 10 patients, the bone marrow aspirates taken after G-CSF administration showed increases in band neutrophil and myelocyte percentages. In conclusion, MVP treatment of patients with NSCLC at 21-day intervals is possible with the support of G-CSF.
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PMID:The use of granulocyte colony-stimulating factor to shorten the interval between cycles of mitomycin C, vindesine, and cisplatin chemotherapy in non-small-cell lung cancer. 128 46

The efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rh G-CSF, KRN8601) given subcutaneously was evaluated in patients with advanced lung cancer undergoing intensive chemotherapy. Twenty-nine and 30 patients with or without prior therapy were enrolled in this study. At dose levels of 50, 90 and 130 micrograms/m2 of rh G-CSF for 14 consecutive days after chemotherapy, the mean neutrophil nadir counts, the mean neutrophil nadir ratios and the duration of neutropenia (days of less than 1000/mm3) were significantly improved. No significant differences were seen in frequency and duration of febrile episodes (greater than 38 degrees C). When rh G-CSF is given subcutaneously, the dose required for an equal effect in alleviating neutropenia is 50% of that required when it is given intravenously. The monocyte counts in the peripheral blood were also significantly increased after chemotherapy cycles with rh G-CSF. The cumulative plasma concentration of rh G-CSF showed a decrement after 7-9 days despite maintenance of the same dose of rh G-CSF for the entire 14 days. In conclusion, 50-130 micrograms/m2 of sc rh G-CSF increased the neutrophil nadir count and shortened the duration of neutropenia in patients undergoing intensive chemotherapy for lung cancer without intolerable side effects.
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PMID:Subcutaneous administration of recombinant human granulocyte colony-stimulating factor (KRN8601) in intensive chemotherapy for patients with advanced lung cancer. 170 15

Peripheral blood has become an alternative to bone marrow as a source of stem cells for transplantation. One of the major disadvantages of peripheral blood as a source is the low concentration of stem cells. For successful engraftment, the infusion of at least 6 x 10(8) nucleated cells per kg is required, a cell number obtained by 6-8 cell pheresis sessions. This cell number contains approximately 0.1% CD34 cells equivalent to 600,000 CD34 cells. It is known that chemotherapy and hematopoietic growth factors increase the concentration and total number of progenitor cells in the peripheral blood. In breast and lung cancer patients we are using two cytoreductive regimens: cytoxan 2 g/m2 + platinol 90 mg/m2, and VP-16 600-900 mg/m2+ platinol 90 mg/m2, respectively, in conjunction with G-CSF for stem cell mobilization. At the time of hematopoietic recovery, between day 13 and 16, the absolute number of CD34+ cells increases in 75% of the patients more than 20-fold, from 5,000 to at least 100,000/ml blood, and to more than 40-fold, to 200,000/ml, in 54% of the patients. Therefore, 3.4-7.5 ml blood contains up to 750,000 CD34+ cells, the minimum number of CD34 cells/kg body weight infused when steady-state collected peripheral blood cells are used. Since we use a minimum of 3 x 10(6) CD34+ cells/kg body weight, 15,000 ml of mobilized blood are required. This amount can often be obtained by collecting 500 ml blood by phlebotomy in 2-3 separate sessions, which is an easy and cost-effective method for the patient.
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PMID:Peripheral blood stem cell collection after mobilization with intensive chemotherapy and growth factors. 752 98

The clinical usefulness of Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF, Filgrastim, GRAN) was evaluated in patients with leukopenia and neutropenia following chemotherapy for non-Hodgkin's lymphoma, lung cancer and breast cancer. During chemotherapy when patients' leukocyte count (WBC) fell below 4.0 x 10(9)/L.rhG-CSF(GRAN) at a dose of 75 micrograms/body.day was given subcutaneously 48 hours after the termination of chemotherapy. The results indicated that rhG-CSF(GRAN) could elevate nadirs of WBC and significantly shortened leukopenic period with WBC below 4.0 x 10(9)/L and expedited the recovery of WBC. rhG-CSF (GRAN)'s side effects were mild.
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PMID:[Clinical study of recombinant human granulocyte colony stimulating factor (rhG-CSF) on leukopenia induced by chemotherapy in cancer patients]. 752 73

Filgrastim, a recombinant human granulocyte colony-stimulating factor (G-CSF), has identical biological activity to that of endogenous human G-CSF, but differs in that it contains an N-terminal methionine residue and is not glycosylated. It principally stimulates activation, proliferation and differentiation of neutrophil progenitor cells and has been evaluated in the treatment of patients with various neutropenic conditions, both iatrogenic and disease-related. Two comparative studies have demonstrated that prophylactic administration of filgrastim 230 micrograms/m2/day significantly reduces the incidence, duration and severity of neutropenia in patients with previously untreated small-cell lung cancer receiving standard-dose chemotherapy with CDE (cyclophosphamide, doxorubicin plus etoposide). Concomitant with the amelioration of neutropenia, the incidence of febrile neutropenia was significantly reduced by 50% and there were 35 and 50% decreases in hospitalisation rates and intravenous antibiotic requirements. Since not all patients receiving standard-dose chemotherapy are at risk of infectious complications, prophylactic filgrastim use may be reserved for those patients who have developed febrile neutropenia during a previous cycle of the same regimen. This strategy may prove less costly, although potential savings must be weighed against a greater risk of patient morbidity and reduced quality of life. When combined with standard intravenous antibiotic therapy, filgrastim further decreases morbidity in patients with established febrile neutropenia and may have a positive impact on overall treatment costs by shortening the length of hospitalisation. Attention is focused on the use of haematopoietic growth factors to support dose-intensification of chemotherapy with a view to improving treatment outcomes in patients with chemo-responsive tumours. Filgrastim, used alone, permits modest increases in dose-intensity and/or dose-escalation of some standard-dose chemotherapy regimens. Moreover, the drug has proven useful as an adjunct to myeloablative chemotherapy followed by stem cell rescue with autologous bone marrow transplantation and/or peripheral blood progenitor cells. However, the impact of these dose-intensification approaches on survival remains to be determined in well-controlled clinical studies. Filgrastim is effective in increasing the neutrophil count and decreasing morbidity in patients with severe chronic neutropenia, including Kostmann's syndrome, and in idiopathic and cyclic neutropenia. In addition, filgrastim has accelerated neutrophil recovery in patients with idiosyncratic drug-induced agranulocytosis. Available data indicate that filgrastim is generally well tolerated. The most frequent adverse reaction is mild to moderate medullary bone pain, reported by approximately 20% of patients, although this can generally be controlled using simple analgesics without the need to discontinue treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Filgrastim. A review of its pharmacological properties and therapeutic efficacy in neutropenia. 753 Jun 30

The population of Japan is gradually aging. Since cancer is mainly a disease of older persons, the incidence of malignancies of all types is expected to increase during the coming decades. Until recently, studies about responses to treatment and toxicity in the elderly patients have been very limited. Many clinical trials have excluded elderly patients with advanced cancer because of decreased tolerance to chemotherapy. In some older cancer patients, however, such exclusion may be inappropriate. Aging is a highly individualized process that cannot be defined by chronological landmarks. The great variation that exists between individual patients in terms of tolerance and responsiveness to chemotherapy seems to be closely related with biological age rather than chronological age of elderly persons. In general, the patterns of disease and stages at diagnosis are not the same for elderly and younger cancer patients. Because bone marrow cellularity diminishes with age, older patients appear to have decreased tolerance to certain anti-cancer agents. Therefore, administration of G-CSF combined with chemotherapy is necessary for elderly patients. A decline in the function of other vital organs also may reduce the efficiency of drug metabolism and excretion, resulting in greater toxic potential. Recently, the use of single-agent oral etoposide has been shown to be an effective palliative therapy for older patients with small-cell lung cancer. The combination of 5-FU with leucovorin has seemed to bring about a good response rate without any remarkable side effect for older patients with gastrointestinal cancer. The oral administration of 5'-DFUR has shown a remarkable prolongation of survival period and improvement of the cachectic status in older cancer patients. Future studies of palliative cancer chemotherapy will be needed to focus on the unique requirement of maintaining QOL in older patients.
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PMID:[Chemotherapy for older cancer patients]. 768 66

A 53-year-old male with von Recklinghausen's disease, diagnosed to have metastatic large cell carcinoma in the left supraclavicular lymph node, was admitted for radiotherapy. No other primary lesions were found. Emphysematous bullae in both upper lung fields were seen on chest roentgenograph, and the leucocyte count and G-CSF level were extremely elevated. Later, when metastases appeared, systemic chemotherapy was supplemented, but in vain. An autopsy showed large cell carcinoma of the lung derived from the wall of emphysematous bullae in left lung along with multiple metastases. The presence of von Recklinghausen's disease, emphysematous bullae and lung cancer together are noteworthy.
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PMID:von Recklinghausen's disease with lung cancer derived from the wall of emphysematous bullae. 806 96

The incidence of lung cancer is increasing, and therapy for patients with this disease is not satisfactory. Surgery is done for patients with clinical (c)-stage I, II, and resectable stage IIIA non-small cell lung cancer (NSCLC). Chemotherapy, alone or in combination with radiotherapy, is given to patients with unresectable stage IV and stage III NSCLC, respectively. Chemotherapy is an important therapeutic modality for patients with small cell lung cancer (SCLC). CDDP + VP-16 (PVP) and CPA + ADM + VCR (CAV) alternating PVP regimens are standard treatment for patients with SCLC. Chemotherapy and radiotherapy are given to patients with limited disease. To develop more effective treatments, we are investigating (1) the schedule and timing of radiotherapy, (2) combination chemotherapy including new drugs, (3) dose-intensive chemotherapy, and (4) new strategies such as gene therapy. Radiotherapy is commonly used sequentially and the standard fractionation is 2 Gy/fr/day. We are studying other timings, such as concurrent and alternating, and other schedules, such as hyperfractionation and accelerated hyperfractionation. Promising new drugs include paciltaxel, docetaxel, vinorelbine, and CPT-11. These are now used in combination with platinum. To evaluate dose-intensive chemotherapy for SCLC, we are conducting a phase III study comparing CODG + G-CSF with CAV/PVP.
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PMID:[Can improvement in therapy decrease the rate of death due to lung cancer?]. 875 77

This Phase II study was designed to determine the efficacy of two chemotherapy regimens with G-CSF support for patients with advanced non-small cell lung cancer (NSCLC). One-hundred and one patients with Stage IIIB or IV NSCLC and performance status 0-1 were randomized to receive ifosfamide 2.0 g/m2 days 1-3, mesna 400 mg/m2 at 0, 4, 6 h days 1-3, cisplatin 33 mg/m2 days 1-3 or etoposide 200 mg/m2 days 1-3, cisplatin 35 mg/m2 days 1-3. Both groups received G-CSF 5 micrograms/kg SQ day 4 to the post day 11 absolute neutrophil count > 10 000. For the 47 eligible patients receiving ifosfamide/mesna/cisplatin, the response rate was 26% (95% confidence interval: 14-40%) and the median survival 7.5 months (95% confidence interval: 5.8-11.0 months). Grade 3 or worse toxicities were: neutropenia 75%, thrombocytopenia 70%, infection 21%. There were two treatment-related deaths due to infection. For course 1, the median absolute neutrophil count nadir was 1.3, platelet nadir 96 000 and incidence of febrile neutropenia 16%. For the 48 eligible patients receiving etoposide/cisplatin, the response rate was 21% (95% confidence interval: 11-35%) and median survival 5.8 months (95% confidence interval: 4.5-9.7 months). Grade 3 or worse toxicities were: neutropenia 90%, thrombocytopenia 58%, infection 29%. There were three treatment-related deaths due to infection. For course 1, the median absolute neutrophil count was 0.2, platelet nadir 80 000 and incidence of febrile neutropenia 33%. For both ifosfamide/mesna/cisplatin and etoposide/cisplatin, median duration of Grade IV neutropenia was short (< or = 4 days), time to subsequent courses 21 days and dose delivered > 95% of planned dose. Although G-CSF allowed full doses of drugs to be delivered on schedule, both ifosfamide/mesna/cisplatin and etoposide/cisplatin produced response rates and survival similar to other cisplatin-based regimens. In view of the significant cost of G-CSF and no obvious improvement in response rate, survival or toxicity profile, G-CSF cannot be recommended with these chemotherapy regimens for patients with advanced NSCLC.
Lung Cancer 1996 Jun
PMID:A randomized phase II study of ifosfamide/mesna/cisplatin plus G-CSF or etoposide/cisplatin plus G-CSF in advanced non-small cell lung cancer: a Cancer and Leukemia Group B study. 879 13

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


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