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)

A patient with severe neutropenia due to Felty's syndrome had limited stage small cell lung cancer, resulting in a therapeutic dilemma. Because he had a cellular bone marrow and no history of recurrent infection, we decided to administer full doses of cytotoxic chemotherapy with curative intent. A durable remission was achieved without complication, despite persistent severe peripheral neutropenia. It may be possible to administer aggressive chemotherapeutic regimens to selected patients with Felty's syndrome when there is the potential for cure of malignant disease.
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PMID:Small cell lung cancer in a patient with neutropenia due to Felty's syndrome. 255 13

A dose escalation study of teniposide (VM-26) plus cisplatin (CDDP) was carried out using recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 46 previously untreated patients with advanced small cell lung cancer (SCLC). The dose of CDDP was 80 mg/m2/day intravenously (i.v.) (day 1) and VM-26 was escalated from 60 mg/m2/day to 80, 100 and 120 mg/m2/day i.v. x 5 days for four cycles. The dose of rhG-CSF was 90 micrograms/m2/day subcutaneously for 13 days. The feasibility of the regimen at the starting dose level of VM-26 with or without rhG-CSF was initially examined in 10 patients chosen through random allocation. WHO grade 4 neutropenia was observed in 17% (three out of 18 courses) of patients in the rhG-CSF group and in 63% (12 out of 19 courses) of the control group (P < 0.01). The number of patients with febrile episodes (> 38 degrees C) over the four courses of chemotherapy was 1 in the rhG-CSF group and 4 in the control group. According to these results, all 36 patients received rhG-CSF in the dose escalation stage. The incidence of WHO grade 4 neutropenia at the dose levels of 60, 80, 100 and 120 mg/m2/day of VM-26 was 66, 57, 76 and 85%, respectively (P > 0.1). The incidence of grade 4 thrombocytopenia was 19, 31, 18 and 46%, respectively (P > 0.1). The overall response rate was 100% in patients with limited stage SCLC and 83% in patients with extensive stage SCLC. The actual administered VM-26 dose per week at the dose level of 100 mg/m2/day was 1.6-fold higher than the planned starting dose (60 mg/m2/day) per week. At the dose level of 120 mg/m2/day, 50% of patients developed WHO grade 4 leucopenia, which lasted longer than 1 week and 67% of the patients had WHO grade 3 or 4 diarrhoea. At this same dose, all patients had at least one febrile episode (> 38 degrees C), and 1 patient died of cerebral bleeding with severe thrombocytopenia. The median survival time of all patients was 451 days (411 days, extensive disease; 497 days, limited disease). VM-26 plus CDDP with rhG-CSF was active in previously untreated patients with SCLC. The recommended dose of VM-26 in combination with CDDP for a phase II study is 100 mg/m2/day for 5 days with rhG-CSF support.
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PMID:A study of dose escalation of teniposide (VM-26) plus cisplatin (CDDP) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced small cell lung cancer. 751 56

To improve the prognosis of limited stage small cell lung cancer (LS-SCLC) the addition of concurrent thoracic radiotherapy to a platinum-containing regimen is important. In the Netherlands, we initiated a multicenter, phase II study, of the combination of four cycles of carboplatin (AUC 5), paclitaxel (200 mg m(-2)) and etoposide (2 x 50 mg orally for 5 days) combined with 45 Gy (daily fractions of 1.8 Gy). The radiation was given to the involved field and concurrently with the second and third chemotherapy cycle. Patients with a partial or complete response received prophylactic cranial irradiation to a dose of 30 Gy. From January 1999 to December 2001, 37 of the 38 patients with LS-SCLC entered were eligible for toxicity analysis and response. Grade 3 and 4 haematological toxicity occurred in 57% (21/37) with febrile neutropenia in 24% (9/37). There were no treatment-related deaths or other grade 4 toxicity. Grade 3 toxicities were oesophagitis (27%), radiation pneumonitis (6%), anorexia (14%), nausea (16%), dyspnea (19%) and lethargy (22%). The objective response rate was 92% (95% confidence interval (CI) 80-98%) with a median survival time of 19.5 months (95% CI 12.8-29.2). The 1-, 2- and 5-year survival rate was 70, 47 and 27%, respectively. In field local recurrences occurred in six patients. Distant metastases were observed in 19 patients of which 13 in the brain. This study indicates that combination chemotherapy with concurrent involved-field radiation therapy is an effective treatment for LS-SCLC. Despite PCI, the brain remained the most important site of recurrence.
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PMID:Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study. 1759 61

There is paucity of data in the literature regarding the safety of combining granulocyte colony stimulating factor (G-CSF) during chemo-radiotherapy (CTRT) in lung cancer patients. The ASCO 2006 recommendations advise against use of CSFs during concomitant mediastinal CTRT. The only randomised study evaluating CSFs in this context showed significant increase in grade 3/4 thrombocytopenia and an excess of pulmonary toxic deaths. In the context of a phase II trial, 38 patients with limited-stage small cell lung cancer were randomised to receive once-daily (66 Gy in 33 fractions) or twice-daily (45 Gy in 30 fractions) radiotherapy. Radiotherapy (RT) was given concurrently with cisplatin and etoposide. G-CSF was given as primary or secondary prophylaxis or as a therapeutic measure during an episode of febrile neutropenia according to local protocols. Common terminology criteria for adverse events (CTCAE) v3.0 was used to record toxicity. Thirteen (34%) of 38 patients received G-CSF concurrently with RT. With a median follow-up of 16.9 months, there were no treatment related deaths reported. Seven (54%) patients experienced grade 3/4 thrombocytopenia and 5 (38%) experienced grade 3/4 anaemia. Thirty-one percent required platelet transfusions. No episodes of bleeding were observed. There were no cases of grade 3/4 acute pneumonitis. These data suggests that with modern three-dimensional (3D) conformal RT, G-CSF administration concurrently with CTRT does not result in the increase risk of pulmonary toxicity, but does increase the risk of thrombocytopenia. Whether the risks of thrombocytopenia are outweighed by the outcome of timely early concurrent CTRT is being evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563) in which G-CSF is permitted during thoracic irradiation.
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PMID:Use of G-CSF during concurrent chemotherapy and thoracic radiotherapy in patients with limited-stage small-cell lung cancer safety data from a phase II trial. 2135 20

We carried out a prospective phase II study of patients with limited stage small cell lung cancer (LS-SCLC) assigned to receive stereotactic body radiotherapy (SBRT) concurrently with cisplatin-based chemotherapeutic regimen with OS and PFS as the primary study endpoints. Patients with pathologically proven LS-SCLC received 4-6 cycles of cisplatin 75 mg/(m(2)/day) given intravenously on day 1 and etoposide 80 mg/(m(2)/day) given intravenously on days 1-5, both at 3 weekly intervals. SBRT at a dose of 4,000-4,500 cGy in ten fractions was given concurrently with chemotherapy starting on day 1. The Kaplan-Meier curve and life tables were used to describe survival data. Adverse events were evaluated according to the common terminology criteria for adverse events version of the radiation therapy oncology group (RTOG). Twenty-nine patients were included and followed up for a median duration of 19 (range 10-85) months. The median OS was 27 (95% CI 20.2-33.8) months. The median PFS was 12 (95% CI 4.2-19.8) months. No grade 4 adverse events were observed. Grade 3 adverse events occurred in only 5 (13.8%, 5/29) patients. Neutropenia of any grade was observed in 6 (15%, 6/29) patients, with grade 3 neutropenia only seen in one (3.4%, 1/29) patient. The combination of chemotherapy and early concurrent SBRT could be a safe and effective treatment for LS-SCLC patients. Our study confirmed that SBRT with concurrent chemotherapy is another new treatment option for LS-SCLC patients.
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PMID:Stereotactic body radiotherapy with concurrent chemotherapy extends survival of patients with limited stage small cell lung cancer: a single-center prospective phase II study. 2541 52

At present, concurrent chemoradiotherapy (CRT) is considered the standard treatment of limited-stage small cell lung cancer (LS-SCLC). However, LS-SCLC is highly heterogeneous in the T stage, N stage, and prognosis. Increasing evidence has shown that individual treatment should be considered when treating LS-SCLC patients. The aim of the present study was to explore the optimal combination model of thoracic radiotherapy (TRT) and chemotherapy in N3 LS-SCLC. We retrospectively analyzed 93 N3 LS-SCLC patients treated in the Department of Oncology of Binzhou Medical University Hospital (Shandong, China) between March 2010 and October 2015. A total of 52 (52/93; 55.9%) patients received sequential CRT, and 41 (41/93; 44.1%) patients received concurrent CRT. All patients received 4-6 cycles of chemotherapy and TRT (50-60 Gy). The median follow-up time was 25.4 months (range was 6-65 months).The overall response rate was 88.5% in the sequential CRT group (9.6% complete response rate and 78.8% partial response rate) and 90.2% in the concurrent CRT group (14.6% complete response rate and 75.6% partial response rate). The PFS and OS were 15.4 months and 19.1 months in sequential CRT group, and 16.9 months and 20.5 months in concurrent CRT group. There was no significant difference in treatment response rate, PFS, and OS between sequential and concurrent CRT patients. The most common treatment-related toxicities were nausea/vomiting, neutropenia, and esophagitis. In conclusion, when concurrent CRT is performed in N3 LS-SCLC patients, tolerance to treatment should be fully considered. In our study, sequential CRT and concurrent CRT showed the same efficacy, and sequential CRT demonstrated better tolerance. However, these results require confirmation in future follow-up studies.
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PMID:Sequential Versus Concurrent Thoracic Radiotherapy in Combination With Cisplatin and Etoposide for N3 Limited-Stage Small-Cell Lung Cancer. 3295 52