Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to evaluate tolerability and efficacy of Leucomax (Sandoz/Schering Plough) used for neutropenia in patients with small cell lung cancer (SCLC) treated with etoposide and cisplatin. The potential influence of granulocyte-macrophage colony stimulating factor (GM-CSF) on chemotherapy relative dose intensity (RDI) was also evaluated. The chemotherapy used was the following, cisplatin 50 mg m-2 i.v. 1 and 7 day, etoposide 170 mg m-2 i.v. 3-5 days, q 3-4 weeks. Patients received a median of six cycles (range 2-8) over 4-36 weeks (median: 20). Thirty-two consecutive patients were treated, six were excluded. Eleven patients received GM-CSF 5 micrograms kg-1 s.c. due to absolute neutrophil count (ANC), 1000/mm3 until recovery (ANC > 2000 mm3) or during 7 days, and thereafter prophylactically 24 hours post subsequent chemotherapy cycles for 7 days. Four patients received single GM-CSF course during the terminal disease phase. In 11 patients, there was no neutropenia requiring GM-CSF during the whole treatment course. Toxicity of chemotherapy was high, including thrombocytopenia, neutropenia, anaemia, mucositis, fever and hypotension. GM-CSF toxicity was the following, first dose reaction-one patient, local erythema-two patients, arthralgia-one patient, hypotension, chills, fever requiring GM-CSF discontinuation one patient RDI of cisplatin/etoposide was 0.77/0.62 in GM-CSF group, and 0.90/ 0.80 in patients who didn't receive Leucomax. Overall objective response rate to chemotherapy and complete response rate were 80% (21/26), 26% (7/26) and median survival of all patients was 10 months. Median disease free survival was 8 months. Four patients are alive, two patients lost during progression, 20 died. Administration of GM-CSF did not appear to improve RDI of chemotherapy, overall response rate (RR) nor survival in this phase I/II clinical study. RDI of chemotherapy was reduced in patients receiving GM-CSF due to thrombocytopenia and/or extrahaematologic toxicity of chemotherapy.
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PMID:Tolerability and efficacy of GM-CSF [Leucomax] in patients with small cell lung cancer treated with intensive chemotherapy. 915 70

Gemcitabine is a novel pyrimidine nucleoside whose activity has been demonstrated on solid tumors. We report here the results of a multicentre phase II trial of gemcitabine in chemonaive patients with inoperable non small cell lung cancer (NSCLC). Gemcitabine was given weekly at a dose of 1,250 mg/m2 administered as a 30 min intravenous infusion, for 3 weeks followed by 1 week of rest (1 cycle). All the 161 patients included were evaluable for toxicity and 151 of them were evaluable for efficacy. The majority of patients had a stage IIIb (31.1%) or stage IV (64.6%) disease; 10.6%, 83.2% and 6.2% of patients had a WHO performance status (PS) 0, 1, and 2, respectively. Adenocarcinoma accounted for 52.2% of cases and squamous cell carcinoma for 43.5% of cases. Three complete responses and 30 partial responses gave an objective response (OR) rate of 21.8% (95% confidence interval; 15.5-29.3%). All responses were validated by an independent Oncology Review Board. Median duration of response was 7.6 months. Median time to progression was 4.6 months (3.3 months in non responders and 7.6 months in responders). Median survival was 7.3 months in non responders and 13.4 months in responders (p < 0.001), which gave an overall median survival of 8.9 months (95% CI: 0.1-21.9 months) in the entire study population. An improvement of symptoms and personal state was also observed. Treatment was well tolerated. Neutropenia was the only dose limiting toxicity. WHO grade 3 or 4 neutropenia occurred in 19.6% and 5.7% of patients, respectively. With a 21.8% OR rate, this multicentre study confirms the activity of gemcitabine as a single agent in patients with inoperable NSCLC. Its good tolerance and original mode of action make gemcitabine a drug of choice in the therapeutic strategy of these tumors.
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PMID:[A phase II multicenter study of gemcitabine in non small cell lung cancers]. 920 75

Twenty-two eligible patients with previously untreated extensive small cell lung cancer received intravenous vinorelbine 30 mg/M2 each week until progression. Response was assessed every 4 weeks by chest x-ray or every 8 weeks by CT scan. All responses had to be "confirmed" at all involved sites at least 4 weeks later. Fourteen patients were male and 8 were female with a median age of 64.5 years (range 38-76). Fifteen patients were Caucasian and 7 were African-American. One patient had a "confirmed" partial response, 3 had unconfirmed responses, 13 had stable or progressive disease, and 5 did not have adequate data. The median progression-free survival was 3 months with a median overall survival of 8 months. Thirteen patients experienced 22 episodes of grade 3 toxicity, more than half due to leukopenia and neutropenia, and 1 due to paresthesias. Of 4 episodes of grade 4 toxicity, 1 was due to leukopenia and 3 were due to hyponatremia which was not due to vinorelbine. Significant thrombocytopenia did not occur. The activity of single agent vinorelbine in untreated small cell lung cancer was disappointing when analyzed by Southwest Oncology Group (SWOG) criteria. The median survival in this trial was similar to that found in other SWOG trials using cisplatin based front line therapy and thus confirms previously reported findings that initial treatment with a phase II agent followed by a cisplatin based regimen at progression does not adversely affect overall survival in this population of patients.
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PMID:A phase II trial of intravenous vinorelbine in previously untreated patients with extensive small cell lung cancer, a Southwest Oncology Group study. 922 Feb 95

This study involved 25 elderly (> 65 years old) patients (pts) with unresectable non small cell lung cancer (NSCLC) who were not eligible for polychemotherapy. The diagnosis of NSCLC was histologically or cytologically documented, and all of them had measurable or evaluable disease. The median age of the patients was 71 (range 65-77); 9 had been pretreated. The pts received 25 mg/m2 of vinorelbine weekly or bi-weekly depending on the results of blood tests. The treatment continued until disease progression or tolerance. No complete response was achieved: 3 pts (12%) had a partial response (RP) (8-12-14 months), 13 (52%) stable disease (SD) with an improvement in symptoms, such as cough and/or pain, and 9 pts (36%) progressed. Compliance with the therapy was acceptable. The main toxicity was hematological: neutropenia was observed in 16 pts, with only 1 case of grade 4 neutropenia without sepsis; grade 1-2 anemia occurred in 8 patients. The other toxicities included grade 1-2 neurotoxicity in 8 pts, chemical phlebitis in 2 pts and grade 3 cardiotoxicity reversible with medical treatment in 1 patient. The median survival time was 10 months (lower quartile 5 months, upper quartile 23 months) (Kaplan and Meyer method). Vinorelbine can be considered a rational choice in elderly pts with advanced NSCLC who are not suitable for aggressive polychemotherapy, with the aim of improving their quality of life in terms of symptoms and outpatient treatment.
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PMID:Vinorelbine chemotherapy in non small cell lung cancer: experience in elderly patients. 926 13

We initiated a phase II pilot study to determine whether adding paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to combination carboplatin/etoposide is tolerable and active in patients with advanced non-small cell lung cancer and extensive small cell lung cancer. Patients were given carboplatin (area under the concentration-time curve of 6) followed by etoposide 80 to 100 mg/m2 intravenously on days 1 through 3 followed by paclitaxel 200 mg/m2 intravenously over 3 hours on day 3. On days 4 through 18, granulocyte colony-stimulating factor 5 microg/kg was administered subcutaneously. Each cycle was repeated every 21 days. Fourteen patients have been accrued to the study and 12 were evaluated for toxicity, the first 10 of whom were treated with 80 mg/m2 etoposide. Among the first 10 evaluable patients, significant grade 4 neutropenia occurred in one patient, grade 4 thrombocytopenia in three patients, grade 2 neuropathy in two patients, and grade 3 neurotoxicity in two patients. None of the four patients with non-small cell lung cancer responded to treatment, while six of seven small cell lung cancer patients have obtained major responses to therapy. We have increased the etoposide dose to 100 mg/m2 in subsequent patients. The combination chemotherapy regimen of carboplatin, etoposide, and paclitaxel is tolerable and active in patients with small cell lung cancer.
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PMID:A phase II study evaluating the efficacy of carboplatin, etoposide, and paclitaxel with granulocyte colony-stimulating factor in patients with stage IIIB and IV non-small cell lung cancer and extensive small cell lung cancer. 933 Nov 37

Carboplatin/etoposide is an active regimen in the treatment of small cell lung cancer. This phase II trial evaluated whether adding paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this two-drug combination might increase its efficacy. Since April 1996, 55 patients were entered into the ongoing protocol. To date, 35 patients are evaluable for efficacy and toxicity. Most of the evaluable patients are male (28). The patients' median age is 60 years (range, 36 to 74 years); 32 patients have Eastern Cooperative Oncology Group performance status ratings of 1, and the balance are Eastern Cooperative Oncology Group performance status 0. All patients had limited-stage disease. Patients received paclitaxel 175 mg/m2 via 1-hour intravenous infusion on day 1, carboplatin dosed to an area under the concentration-time curve of 5, also on day 1, and oral etoposide 100 mg on days 2 through 8. Overall, 31 patients responded to paclitaxel/carboplatin/etoposide therapy, including complete response in 13 patients (37.1%) and partial response in 18 patients (51.4%). Disease was stable in three patients (8.6%) and disease progressed in one (2.0%). Hematologic toxicity included neutropenia (World Health Organization grade 3 in 24.1% of patients, grade 4 in 31.3%), anemia (4% grade 3, no grade 4), and thrombocytopenia (3.2% grade 3, 2.1% grade 4). Nonhematologic adverse events included minor nausea/vomiting (1.5% grade 3, 9.2% grade 2), polyneuropathy (2.3% grade 2, 17.5% grade 1), and myalgia/arthralgia (8.2% grade 2, 16.4% grade 1). Paclitaxel/carboplatin/etoposide is active in small cell lung cancer with moderate toxicity and good subjective tolerance. There were no life-threatening hematologic or nonhematologic complications in this phase II trial.
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PMID:Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. 933 Nov 41

Hematopoietic growth factors are cytokines able to modulate proliferation and differentiation of bone marrow progenitors. We have reviewed the effectiveness of GM-CSF in protecting marrow from chemotherapy-induced neutropenia, mainly in the setting of cyclic polychemotherapy; in particular, studies employing low doses of GM-CSF have been considered. G-CSF or GM-CSF may be particularly useful in situations in which the likelihood of a clinically relevant neutropenia is high, both because of higher dose intensity (obtained by intensification of doses of each cycle or by shortening of intervals between cycles) or because of pretreatment patient characteristics (old age, poor performance status, previous extensive chemotherapy or radiotherapy, experience of neutropenia in the previous cycles). GM-CSF at the conventional dose of 5 micrograms/kg was utilized to increase the etoposide dose to 900 mg/m2 in a chemotherapy program including also carboplatin and ifosfamide in patients with small cell lung cancer. In a randomized study by Ardizzoni et al., the administration of GM-CSF at the dose of 10 micrograms/kg following CEF program (cyclophosphamide, epirubicin and fluorouracil) was effective in reducing from 20 to 16 days the time interval among cycles. Since there is a relationship between GM-CSF dose levels and toxicity, it is attractive to investigate whether GM-CSF at doses lower than 5 micrograms/kg retains its myeloprotective effects, with a substantial reduction in its toxic effects. Grem et al. have observed that 3 micrograms/kg GM-CSF may allow the administration of 425 mg/m2 fluorouracil for five days; Reed et al. demonstrated that 600 mg/m2 carboplatin may be safely administered if protection with 3 micrograms/kg GM-CSF is applied; Kehoe et al. achieved acceleration of cyclophosphamide-cisplatin combination by GM-CSF at the dose of 3 micrograms/kg. We conclude that low dose GM-CSF deserves further evaluation in order to determine effectiveness and potential applications in the clinical practice.
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PMID:[Low-dose GM-CSF and dose intensity of antineoplastic agents]. 944 57

Twenty-three patients with small cell lung cancer were treated with combination chemotherapy consisting of Cisplatin at 100 mg/m2 given by 2 hours intravenous infusion on day 1 and oral etoposide 25 mg/caplet given twice a day for 21 days repeated every 28 days for 6 cycles. Of 23 cases, four cases were not evaluable due to early death (three of them died from febrile neutropenia). Median age of the patients was 59 years (range = 45-76 years). Five cases were female and eighteen cases were male. Median Karnofsky performance status was 70 per cent (range = 50-90%). Five cases were extensive disease and eighteen cases were limited disease. Of 5 extensive disease cases, 1 complete response (20%) and 3 partial responses (60%) were achieved. Of 14 limited disease patients, 1 complete response (7.1%) and 11 partial responses (78.6%) were achieved. Hematologic toxicities were severe causing three patients to die because of febrile neutropenia, nine cases (10.7%) had grade 3 and 4 neutropenia. Grade 3 and 4 anemia and thrombocytopenia were seen in 28.6 per cent and 8.3 per cent respectively. Median survival time of all cases was 7 months. Thus, the combination of intravenous cisplatin and prolonged administration of oral etoposide could be administered to small cell lung cancer patients with high response rate, however, because of its severe toxicities, special caution should be considered and the optimal duration of oral etoposide should be evaluated.
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PMID:Preliminary study of efficacy of intravenous cisplatin plus oral etoposide in small cell lung cancer. 947 Mar 20

MVP chemotherapy (mitomycin C 8 mg m(-2), courses 1, 2, 4 and 6, vinblastine 6 mg m(-2), cisplatin 50 mg m(-2)) is an active low-toxicity regimen in non-small-cell lung cancer (NSCLC). Based on the single-agent activity of these agents in SCLC, we have conducted a phase II trial of MVP in SCLC. Fifty chemo-naive patients with SCLC were entered in this trial. There were 33 men and 17 women with median age 66 years (range 46-83 years); 18 patients had limited disease (LD) and 32 extensive disease (ED). WHO performance status (PS) was: three patients PS 0, 33 patients PS 1, ten patients PS 2, four patients PS 3. A maximum of six cycles was given in responding patients. On completion of chemotherapy, patients with LD obtaining complete response (CR)/good partial response (PR) received thoracic irradiation and those obtaining CR were offered entry into the ongoing MRC Prophylactic Cranial Irradiation Trial. The overall response was 79% with 17% CR and 62% PR. For LD patients, 38% obtained CR but for ED only one patient achieved CR. Median response duration for LD patients was 8 months and for ED patients 5 months. Median survival was 10 months for LD patients and 6 months for ED patients. There was complete resolution of symptoms in 24%, partial improvement in 68%, no change in 2% and progressive symptoms in 6%. As regards toxicity, 24% developed WHO grade 3/4 neutropenia, 16% grade 3/4 thrombocytopenia and 6% significant hair loss. Two patients died during the first week of treatment with neutropenic infection. Quality of life using the EORTC questionnaire (QLC-C30) with lung cancer module demonstrated significant improvements from baseline levels in emotional and cognitive functioning, global QOL, of pain, dyspnoea and cough. MVP, an effective palliative regimen for NSCLC, is also active against SCLC with low toxicity and merits comparison with more toxic conventional schedules.
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PMID:A pilot study of MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in small-cell lung cancer. 966 76

Neutropenia is the most common dose-limiting toxicity of conventional chemotherapy. The colony-stimulating factors (CSFs), granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF, stimulate proliferation and maturation of myeloid progenitors and have been effective in reducing neutropenia and its complications. The primary use of CSFs in patients receiving chemotherapy for small cell lung cancer has resulted in a reduction in the incidence of febrile neutropenia, a decrease in the duration of grade IV neutropenia, and a reduction in hospitalization time and antibiotic use. Although CSF use allows for higher dose intensity, a survival benefit has not been proven. The use of CSFs after the occurrence of neutropenic fever decreases the duration of grade IV neutropenia, but effects on hospitalization and antibiotic use are less well-defined. The therapeutic use of CSFs in the setting of established neutropenia, regardless of the presence or absence of fever, is not supported in the literature. The administration of CSFs to patients with acute myeloid leukemia is safe in that no trial has demonstrated evidence of leukemic stimulation with these drugs. As in other settings, the duration of neutropenia is shortened if CSFs are used postchemotherapy with evidence of clinical benefit. CSFs also decrease chemotherapeutic toxicity via other mechanisms. The use of G-CSF reduces the incidence of mucositis, in normal donors enhances the yield of leukapheresis for granulocyte transfusion, and is beneficial in the autologous transplant setting. These effects of CSFs in mitigating chemotherapeutic toxicity are reviewed.
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PMID:Hematopoietic growth factors in the reduction of chemotherapeutic toxicity. 978 94


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