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)

Extensive-stage small cell lung cancer (ES-SCLC) remains a therapeutic challenge to the medical oncologists. We evaluated the triplet combination of paclitaxel (175 mg/m(2) over 1 h), ifosfamide (2.5 gm/m(2) over 1 h) and carboplatin (AUC=6 over 0.5 h) (PIC) all given on day 1 of a 21 day schedule. Thirty-five patients were entered with a median age of 59 years (range 40-79). The ECOG PS was 0-1 in 86%. A median of 6 cycles were delivered (range 1-6). The principal toxicity was neutropenia with 66% of patients experiencing grade 4 neutropenia. Only 9% of patients experienced febrile neutropenia. One treatment-related death (3%) due to neutropenic sepsis occurred. Non-hematologic toxicity was minimal. The overall response rate was 71% (15% complete response, 56% partial responses). Quality of life appeared to be stable across time. The median survival time was 9.5 months (95% confidence interval (CI), 6.7-13.2 months) with a 1- and 2-year survival rates of 43% (95% CI, 26-59%) and 16% (95% CI, 2-30%). PIC has activity in ES-SCLC and is associated with a response rate and survival profile similar to other combinations in this disease setting. This regimen has a tolerable toxicity profile and a favorable and convenient administration schedule.
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PMID:Phase II trial of paclitaxel, ifosfamide, and carboplatin in extensive-stage small cell lung cancer. 1266 13

The purpose of this study was to evaluate the efficacy and safety of docetaxel as second-line chemotherapy for advanced non-small cell lung cancer (NSCLC). Thirty-four patients with advanced NSCLC received docetaxel 75 mg/m2 (1-h intravenous infusion) every 3 weeks, with corticosteroid premedication. Of 28 evaluable cases, 18 were adenocarcinoma, 3 squamous cell, 3 large cell and 4 undifferentiated carcinoma. There were 16 male and 12 female patients with a median age of 55 (37-73) years and their median Karnofsky performance status was 70 per cent (60-90%). Five cases (19.2%) had liver metastases, 3 (11.5%) brain metastases, 6 (23%) bone metastases, and 17 (65.3%) metastatic nodules in the lung. Seventeen cases (50%) had received cisplatin-based and 12 (12/34, 35.3%) paclitaxel plus carboplatin prior to entering the present study. Besides chemotherapy, seven cases had received prior thoracic irradiation and two whole brain irradiation. Two cases had prior surgery for malignant pleural effusion and one had thoracotomy for the resection of the primary tumor. The time from the last dose of chemotherapy to the start of this study was less than 6 months in 20 cases, 6-12 months in 9, 12-24 months in 3 and more than 24 months in 2 cases. One patient with initial small cell lung cancer had developed NSCLC before entering this study. Three out of 28 cases achieved partial response (10.7%) and 13 out of 28 achieved stable disease (46.5%). The median survival time was 23.8 weeks. Neutropenia, grade 3 and 4 occurred in 38.8 per cent of all cycles. Skin rashes, diarrhea, asthenia, alopecia, neuropathy and edema were common non-hematologic toxicities. Docetaxel should be considered as second line chemotherapy in advanced NSCLC when primary chemotherapy including cisplatin and/or paclitaxel had failed.
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PMID:Docetaxel as second-line chemotherapy for advanced non-small cell lung cancer. 1267 67

The purpose of the study was to evaluate the combination of gemcitabine and vinorelbine in the treatment of patients with relapsed or refractory small cell lung cancer. Between March 1998 and February 1999, 30 patients with relapsed or refractory small cell lung cancer who had received treatment with one previous combination chemotherapy regimen entered this multicenter, community-based clinical trial. All patients had received previous platinum/etoposide combination chemotherapy; in addition, 12 patients had received paclitaxel as part of their first-line therapy. All patients received gemcitabine 1000 mg/m2 and vinorelbine 20 mg/m2 on days 1, 8, and 15 of each 28-day cycle. Patients were reevaluated for response after two cycles of therapy; those with objective response or stable disease continued treatment for six courses or until disease progression. Three of 28 evaluable patients (10%) had partial responses to treatment. None of the 17 patients with refractory disease responded, while 3 of 12 patients (25%) with relapsed disease had partial responses. Median survival was 5 months. Treatment was generally well tolerated; myelosuppression was the major toxicity, but only two patients developed febrile neutropenia, and there were no treatment-related deaths. Non-hematologic toxicity was uncommon; alopecia did not occur with this regimen. The activity of gemcitabine and vinorelbine in patients with previously treated small cell lung cancer is modest and is limited to patients with relapsed (versus refractory) disease. In patients with relapsed small cell lung cancer, this regimen provides an additional treatment option, with decreased toxicity when compared to other second-line options. However, novel treatment approaches are necessary before substantial improvements in treating this patient population will be realized.
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PMID:Combination chemotherapy with gemcitabine and vinorelbine in the treatment of patients with relapsed or refractory small cell lung cancer: a phase II trial of the Minnie Pearl Cancer Research Network. 1274 84

We examined the safety and efficacy of the combination of irinotecan plus carboplatin in patients with refractory or relapsed small cell lung cancer (SCLC). Patients with previously treated SCLC were eligible. Patients were treated every 3 weeks with carboplatin (with a target area under the concentration versus time curve of 5 mg min/ml using the Calvert formula on day 1) plus irinotecan (50 mg/m(2) on days 1 and 8). From May 2000 to January 2002, 24 patients were eligible. None of the 22 patients achieved a complete response, but 15 achieved a partial response with an overall response rate of 68.2% (95% confidence interval, 45.1-86.1%). In 13 patients with sensitive disease, the response rate was 92.3% (95% confidence interval, 64.0-99.8%). The median survival time (MST) was 194 days (range 27-605 days). The MST did not differ significantly between patients with sensitive disease (245 days) and those with refractory disease (194 days, P=0.88). One patient died of treatment-related sepsis. Grade 3-4 hematologic toxicities included leukopenia in 58% of patients, neutropenia in 63%, thrombocytopenia in 58%, and anemia in 67%. Grade 3 diarrhea developed in 21% of patients and grade 3-4 infection in 13%. No patients had grade 4 diarrhea or grade 3-4 nausea and vomiting. This regimen is effective and well tolerated in patients with relapsed or refractory SCLC. However, the search for even more active regimens should be continued.
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PMID:Phase II study of irinotecan and carboplatin in patients with the refractory or relapsed small cell lung cancer. 1278 33

This phase II study was conducted to investigate the efficacy and safety of irinotecan (CPT-11) and ifosfamide as second-line chemotherapy for relapsed small cell lung cancer (SCLC). Eligibility criteria included histologically or cytologically confirmed SCLC, prior chemotherapy including platinum + etoposide, and measurable or evaluable disease. CPT-11 (80 mg/m(2)) was administered intravenously on days 1, 8 and 15, while ifosfamide (1.5 g/m(2)) was given on days 1 through 3 every 4 weeks. Thirty-four patients (29 men) with a median age of 69 years (range 42-77) and a median Eastern Cooperative Oncology Group (ECOG) performance status of 1 (range 0-2) were enrolled. The response rate was 52.9% (95% confidence interval: 29.8-64.9%) with 2 complete responses and 16 partial responses. Our analyses of prognostic factors showed risk factors assessed before receiving second-line chemotherapy, which were the number of metastatic sites, performance status and the type of relapse. WHO grade 3-4 neutropenia was recorded in 52.9% of the patients, grade 3 diarrhea in 5.9%. The combination of CPT-11 and ifosfamide demonstrated clinical efficacy in relapsed SCLC with a favorable toxicity profile, particularly for performance status 0-1 and sensitive cases with only one metastatic site.
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PMID:Combination chemotherapy with irinotecan and ifosfamide as second-line treatment of refractory or sensitive relapsed small cell lung cancer: a phase II study. 1288 56

Amrubicin is a completely synthetic anthracycline derivative. In contrast, however, the anthracyclines used clinically thus far have been produced by fermentation or semisynthesis. Amrubicin is structurally distinguishable from other anthracyclines by the amino group at the 9-position and its unique sugar moiety. Amrubicinol, the C-13 hydroxy- metabolite of amrubicin, is associated with a 5 to 200 times greater cytotoxicity than amrubicin. Amrubicin exhibited superior in vivo antitumor activity to doxorubicin in the human tumor xenograft model. Using this model, the level of amrubicinol (active metabolite) was shown to be higher than that of doxorubicin in tumor tissues, but lower in normal tissues. These results suggest potent therapeutic activity for amrubicin because of the selective distribution of its highly active metabolite, amrubicinol, in tumors. These anti-tumor effects of amrubicin are considered to be induced by DNA topoisomeraseII inhibition. In clinical studies, amrubicin has demonstrated potent single agent activity as compared to a standard regimen in untreated patients with extensive small cell lung cancer. Its major toxicity was myelosuppression (especially neutropenia).
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PMID:[Profile of the anti-tumor effects of amrubicin, a completely synthetic anthracycline]. 1289 Sep

Granulocyte colony stimulating factor (G-CSF) can reduce the duration of neutropenia following intensive chemotherapy in a variety of settings. The majority of these studies have focused on small cell lung cancer. We review herein published information on costs and cost-effectiveness of G-CSF from clinical studies with patients with small cell lung cancer (SCLC). Medline and Healthstar databases were searched for original research articles that contain cost or cost-effectiveness analyses on the subject. The cost of adjunct treatment with G-CSF was evaluated from four studies of SCLC patients. Benefits included decreased rates of febrile neutropenic events, while cost savings were not identified in three of four studies. These data may be useful to physicians faced with concerns over clinical and economic factors associated with G-CSF use as adjunct therapy for SCLC.
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PMID:Cost analyses of granulocyte colony stimulating factor: a focus on older patients with cancer. 1456 24

We report two cases with small cell lung cancer (SCLC) receiving multicyclic dose-intensified chemotherapy (DI-CT) supported by autologous blood progenitor cell transplantation (ABPCT). Both cases were initially treated with cisplatin (CDDP), etoposide (ETP) and concurrent thoracic irradiation, however they had recurrent disease within a year. After receiving conventional chemotherapy, they underwent multicyclic DI-CT consisting of CDDP, ETP and ifosfamide supported by G-CSF and ABPCT. Definite regression of the tumors was observed. Severe neutropenia and thrombocytopenia were encountered but they were reversible and no life-threatening complications were experienced. These results suggest the feasibility and effectiveness of multicyclic DI-CT and the usefulness of ABPCT as a treatment option for relapsed SCLC.
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PMID:Multicyclic dose-intensive chemotherapy supported by autologous blood progenitor cell transplantation for relapsed small cell lung cancer. 1466 30

Topotecan is the only single-agent therapy approved by the U.S. Food and Drug Administration for the treatment of patients with recurrent small cell lung cancer (SCLC). Poor performance status (PS) at the time of relapse can hinder the ability of a patient to tolerate second-line chemotherapy. To investigate the feasibility of topotecan in the treatment of relapsed SCLC patients with PS 2 scores, we retrospectively analyzed data from five clinical trials that included 479 patients who were treated with single-agent topotecan at a dose of 1.5 mg/m2/day on days 1-5 of a 21-day course. Of these patients, 381 had a PS 0 or 1 and 98 had a PS 2. Topotecan was well tolerated by both patient groups. Hematologic toxicities were generally manageable, and neutropenia was noncumulative. With the exception of grade 3/4 anemia, the incidences of severe hematologic toxicities were not statistically different between the two groups. The nonhematologic toxicity profiles were also similar in the two patient groups. Treatment provided similar benefits, including antitumor response rates and symptom palliation, in PS 0/1 and PS 2 patients. As expected, the median overall survival time was shorter in patients with worse PS scores; the median overall survival times were 36.3 weeks, 25.4 weeks, and 16 weeks for PS 0, PS 1, and PS 2 patients, respectively. In conclusion, treatment with topotecan is feasible and well tolerated in patients with relapsed SCLC with suboptimal PS scores.
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PMID:Topotecan in the treatment of relapsed small cell lung cancer patients with poor performance status. 1504 21

Small cell lung cancer (SCLC) is an aggressive tumor that often metastasizes before the primary cancer is diagnosed. Patients with SCLC are typically elderly and often have comorbidities that may predispose them to adverse events during therapy. Although topotecan (Hycamtin; GlaxoSmithKline; Philadelphia, PA), 1.5 mg/m(2)/day via a 30-minute i.v. infusion on days 1-5 of a 21-day cycle, is a standard therapy for relapsed SCLC, this regimen can result in significant neutropenia, especially in previously treated patients. This hematologic toxicity is noncumulative and reversible, but its management can be challenging in this poor-prognosis population. Therefore, alternate treatment regimens have been investigated. Weekly topotecan (4.0 mg/m(2)) is currently investigational and has shown promising activity and favorable tolerability in patients with relapsed ovarian cancer, another aggressive malignancy with a poor prognosis. Preliminary results from a phase II trial of weekly bolus topotecan (4.0 mg/m(2)) in patients with recurrent SCLC were recently reported, and this regimen was generally well tolerated. Furthermore, weekly topotecan has been successfully included in several combination therapy regimens in patients with a variety of solid tumors. In untreated SCLC patients, a combination regimen of weekly topotecan, paclitaxel (Taxol; Bristol-Myers Squibb; Princeton, NJ), and cisplatin (Platinol; Bristol-Myers Squibb) was explored and found to be well tolerated and active in patients with extensive and limited-stage disease. Further clinical trials of weekly topotecan and regimens that include weekly topotecan in the SCLC setting are warranted.
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PMID:Emerging role of weekly topotecan in recurrent small cell lung cancer. 1561 47


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