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 multi-institutional cooperative group trial was undertaken by the Cancer and Leukemia Group B (CALGB) to evaluate the efficacy of the combination of cisplatin and intravenous etoposide for the treatment of metastatic or recurrent non-small cell lung cancer (NSCLC). The doses used were those previously determined to be the maximally tolerated dose of this drug combination. Forty patients were entered into the trial, 37 of whom were eligible for evaluation. Cisplatin (35 mg/M2/day for 3 days) and etoposide (200 mg/M2/day for 3 days) were administered every 28 days for a planned 6 cycles of therapy. Sixteen of 37 evaluable patients (43%) responded to therapy. Myelosuppression was the dominant toxicity, with 89% of the patients experiencing grade 4 neutropenia, and nearly half grade 3 or 4 thrombocytopenia. Median survival was 8.5 months, with 30% of the patients alive at 1 year and 10% alive at 2 years. Malaise, fatigue, and peripheral neuropathy were the other major toxicities. The combination of etoposide at the dose of 200 mg/M2/day for 3 days and cisplatin at 35 mg/M2/day for 3 days is a highly potent combination against metastatic non-small cell carcinoma.
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PMID:Etoposide (VP-16) and cisplatin at maximum tolerated dose in non-small cell lung carcinoma: a Cancer and Leukemia Group B study. 871 68

This phase II study was designed to utilize conformal radiation therapy with cisplatin and oral etoposide in patients with stage III or locally recurrent non-small-cell lung cancer to determine tolerance and toxicity of therapy. From April 1992-February 1996, 18 patients with pathologically confirmed stage IIIA, IIIB, or locally recurrent non-small-cell lung cancer (NSCLC) were entered on study. Metastatic workup included a CT scan of the thorax and upper abdomen as well as a bone scan. Chemotherapy consisted of IV cisplatin (100 mg/m2) with IV etoposide (25 mg/m2) on day 1; oral etoposide was given (50 mg/m2) days 2-14. Using three-dimensional planning, 40-45 Gy were delivered to the clinical target volume, followed by a boost to the gross tumor volume for a total of 70 Gy. Patients with recurrent disease received 40-50 Gy in total. Eighteen patients were enrolled: 16 patients were treated with curative intent and were evaluable for outcome. Two patients were treated for locally recurrent NSCLC and were not included in the outcome analysis. Stages included IIIA (44%) and stage IIIB (54%). Forty-four percent had T3/4 tumors, and 69% had N2/3 disease. Overall survival at 1 year was 64%, while 2-year overall survival was 50%. Distant metastasis-free survival at 1 year was 67%, and at 2 years 60%. The 1-year chest progression-free survival was 57%, and at 2 years 50%. Sixty-three percent required hospitalization for dehydration or neutropenia. Fifty-six percent developed leukopenia (<1,000 cells/microl) sometime during the therapy. We conclude that concurrent cisplatin and oral etoposide with conformal radiation therapy provide encouraging results in stage III lung cancer. The major toxicities of this therapy included leukopenia, thrombocytopenia, and mucosal esophagitis. Local progression of disease continues to be a problem with the current doses given. Future studies should evaluate dose escalation of radiation therapy with limited volumes, utilizing conformal radiation and chemotherapy to improve local control and potentially impact upon distant metastases.
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PMID:Results of a phase II concurrent chemoradiotherapy study using three-dimensional conformal radiotherapy with cisplatin and oral etoposide in stage III nonsmall-cell lung cancer. 1003 Jun 24

Paclitaxel enhances microtubule assembly and causes a cell cycle arrest in mitosis, the most radiosensitive phase. We conducted this study to improve our understanding of paclitaxel effects in vivo and to determine the maximum tolerated dose of paclitaxel preceding endobronchial radiation therapy (brachytherapy). The treatment consisted of two cycles of paclitaxel infused over 24 hours followed by 192Ir brachytherapy; cycles were repeated every 3 weeks. Tumor samples were obtained at baseline, after each paclitaxel infusion, and 3 weeks after completion of therapy. Twenty-two non-small cell lung cancer patients with a documented endobronchial lesion were enrolled in the study and 20 patients received the therapy with different doses of paclitaxel, initially without and then later with granulocyte colony-stimulating factor (G-CSF) support (5 microg/kg subcutaneously on days 3 to 10). With the starting paclitaxel dose of 135 mg/m2, five of seven patients developed neutropenia and fever, which mandated a dose reduction to 120 mg/m2. At this dose level, three of three patients had neutropenic fever; thus, 120 mg/m2 of paclitaxel was considered above the maximum tolerated dose without G-CSF support. However, with G-CSF support the therapy was well-tolerated without dose-limiting toxicity and accrual is continuing at the paclitaxel 175-mg/m2 dose level. While no patient had achieved systemic tumor response, 11 patients achieved partial response of the endobronchial lesion, which represents 68.8% of 16 patients who received two courses of therapy and 91.8% of 12 patients who had full evaluation by bronchoscopy after completion of therapy. The in vivo paclitaxel effects were studied using the pre- and post-paclitaxel therapy tumor samples in eight patients. Four (50%) patients had a significant increase in mitotic cells after paclitaxel, as assessed by MPM-2 immunostaining that recognizes a large family of mitotic phosphoproteins. A substantial increase in the number of micronucleated apoptotic cells, another paclitaxel effect, was also found in six patients. These results clearly indicate that patients with endobronchial lesions from recurrent NSCLC could not tolerate this combined modality regimen without G-CSF support. However, this group of patients provided a unique opportunity to study in vivo paclitaxel effects in a clinical trial setting.
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PMID:A pilot clinical laboratory trial of paclitaxel and endobronchial brachytherapy in patients with non-small cell lung cancer. 1021 May 51

This trial was initiated to evaluate the toxicity and activity of combination chemotherapy employing cisplatin (CDDP), docetaxel (DCT) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), and to determine the maximum tolerated dose (MTD) of IFX. Chemotherapy-naive patients with advanced or recurrent NSCLC received 60 mg/m(2) DCT followed after a 3-h interval by 60 mg/m(2) CDDP on chemotherapy day 1, and IFX at an escalating dose with mesna protection on days 2-4. The chemotherapy was repeated every 3 weeks. Granulocyte colony-stimulating factor (GCSF) was administered in the event of grade 3 leukopenia/neutropenia. The patients tolerated the treatment well up to level 4 of IFX dosing 1.5 g/day, but not the IFX dose at level 6 (2.0 g/day). Additional patients were enrolled in level 5 (IFX 1.7 g/day) to evaluate the toxicity of the drugs around the MTD. Level 5 was also judged as having exceeded the MTD, with febrile neutropenia and hepatic toxicity being observed as the dose-limiting toxicities. No toxicity-related deaths occurred. The majority of the chemotherapy courses were supported by GCSF administration. A total of 33 eligible patients were entered into the trial; the overall response rate was 10/33 or 30% among all eligible cases, and the rate for patients treated with the MTD or higher (levels 4-6) was 8/24, or 33% (90% confidence limit: 18-52%). The MTD of IFX was 1.5 g/m(2) administered for 3 days in this triplet combination. The clinical activity does not seem to justify the toxicity profile.
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PMID:A phase I/II trial of cisplatin, docetaxel and ifosfamide in advanced or recurrent non-small cell lung cancer. 1155 21

Platinum-based chemotherapy offers a modest survival advantage over best supportive care (BSC) in chemotherapy-naive patients with a good performance status and advanced/metastatic non-small-cell lung cancer (NSCLC). Based on 2 landmark studies that reported improved survival times and quality of life when comparing docetaxel with ifosfamide, vinorelbine, or BSC alone, docetaxel at 75 mg/m(2) given once every 3 weeks has been the standard of care as second-line chemotherapy since 2000. Docetaxel given at this dose and schedule resulted in significant hematologic toxicity, with many patients at risk for neutropenic fever. Pemetrexed is a novel multitargeted antifolate agent with single-agent activity in first- and second-line treatment of NSCLC. A phase III study in 571 patients comparing pemetrexed with docetaxel demonstrated clinically equivalent therapeutic outcomes in second-line treatment of patients with recurrent NSCLC; however, patients on the pemetrexed arm had a more favorable hematologic toxicity profile, with fewer episodes of neutropenia, neutropenic fever, and infections and less use of granulocyte colony-stimulating factor support. Based on these data, pemetrexed is a reasonable second-line chemotherapy option for patients with recurrent, advanced NSCLC.
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PMID:Second-line chemotherapy for non-small-cell lung cancer: recent data with pemetrexed. 1511 29

Docetaxel (Taxotere) is one of the most active new generation chemotherapy agents against advanced non-small cell lung cancer (NSCLC). This study aimed to determine the activity, toxicity and impact on the quality of life (QOL) in patients treated with docetaxel after failure with first-line platinum-based combination chemotherapy. Twenty-one patients with advanced NSCLC who had previously received the platinum-containing regimen were treated with docetaxel 75 mg/m2 every 3 weeks. QOL was assessed at intervals during the treatment period using the Functional Assessment of Cancer Treatment - Lung (FACT-L). Of the 21 patients enrolled, 16 were able to be evaluated for response and 20 were included in the toxicity analysis. The median age was 57 (range, 39-75 years). A median of 3 cycles was given (range, 1-9). Of the 16 evaluatable patients, there was one partial response (6.3%) and 4 with stable disease (25%). The median survival time was 8.1 months and the 1-year survival rate was 25%. Myelosuppression and peripheral neuropathy were the major toxicities. Grade 3/4 neutropenia and paresthesia occurred in 6 patients (30%) and 3 patients (15%), respectively. There was no significant improvement or deterioration in the overall FACT-L, TOI (Trial Outcome Index) and lung cancer symptom scores during the treatment. Symptom improvement was noted, in particular for shortness of breath and weight loss in the majority of patients. It is concluded that docetaxel is a well tolerated second-line treatment for recurrent NSCLC. Of particular importance was that the treatment did not negatively impact the overall quality of life, on the contrary, did palliate some of the lung cancer related dash symptoms in many patients.
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PMID:Doxetaxel in previously treated non-small cell lung cancer patients: clinical efficacy and quality of life. 1590 78

Current options for the second-line treatment of non-small cell lung cancer (NSCLC) include cytotoxic drugs, such as docetaxel and pemetrexed, and targeted therapies. Docetaxel was approved in the United States and Europe in 2000 after two phase III trials showed drug superiority versus best supportive care alone and versus alternative single-agent chemotherapy. Pemetrexed was approved in the United States and Europe in 2004 after a phase III trial showed that, compared with docetaxel, it had comparable activity (median survival time of approximately 8 months in both arms) and a more favorable toxicity profile: grade 3-4 neutropenia was observed in 5.3% versus 40.2% of patients in the pemetrexed and docetaxel arms, respectively, while febrile neutropenia was observed in 1.9% versus 12.7% of patients, respectively. In the United States, gefitinib and erlotinib have also been approved for the treatment of recurrent NSCLC (in 2003 and 2004, respectively), while in Europe the registration of these agents is currently under evaluation. This review focuses on the use of docetaxel and pemetrexed for the second-line treatment of NSCLC and compares these drugs with targeted therapies, highlighting the latest developments in pharmacogenomics that might lead to a more tailored approach to treatment.
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PMID:Second-line treatment options in non-small cell lung cancer: a comparison of cytotoxic agents and targeted therapies. 1647 5

We conducted this phase II study to explore the efficacy and safety of weekly paclitaxel combined with carboplatin in elderly patients with advanced non-small cell lung cancer (NSCLC). Elderly patients (> or = 70 years old) of stage IIIB, IV, or recurrent NSCLC with PS 0 or 1 were enrolled. Patients received paclitaxel at a dose of 70 mg/m2 on Days 1, 8, 15, and carboplatin at the target dose of the area under the curve (AUC) of six on Day 1 every 28 days for at least two cycles. Forty-two patients were enrolled and 40 patients were treated with a median of three cycles (range, 1-5). The overall response rate (ORR) was 45% (95% confidence interval, 30-60%). The median survival time (MST) was 14 months and the 1-year survival rate was 62%. Twenty-eight patients (70%) had grade 3/4 neutropenia and two patients (5%) experienced grade 3 febrile neutropenia. Non-hematological toxicities were generally mild to moderate and grade 3 peripheral neuropathy was seen in one patient (3%). There was one treatment-related death by infection due to neutropenia. Weekly paclitaxel and carboplatin combination chemotherapy was an effective and safe regimen in elderly patients with advanced NSCLC. A randomized trial comparing this treatment with the conventional tri-weekly regimen of paclitaxel and carboplatin is warranted.
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PMID:A phase II study of weekly paclitaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer. 1648 87

We report two cases with recurrent non-small cell lung cancer (NSCLC) successfully treated with cisplatin and S-1 after multiple chemotherapy. A 64-year-old woman was diagnosed with adenocarcinoma, yield-T4N2M1, stage IV. She was treated with cisplatin 60 mg/m(2) (day 8) and S-1 80 mg/m(2) (days 1-21) as sixth-line chemotherapy after treatment with paclitaxel and irinotecan, cisplatin and gemcitabine, docetaxel, gefitinib, and vinorelbine. Chest computed tomography (CT) showed partial response of recurrent tumors. Another woman (56 years old) was diagnosed with adenocarcinoma, yield-T0N1M1, stage IV. She was also treated with cisplatin and S-1 as fourth-line chemotherapy after treatment with nedaplatin and gemcitabine, docetaxel and irinotecan, and gefitinib. Chest CT showed a partial response of recurrent tumors. Additionally, we retrospectively reviewed 10 cases with recurrent NSCLC treated with cisplatin and S-1 during the same period. Grade 3 to 4 hematologic toxicity included neutropenia in 30% of these 10 patients, thrombocytopenia in 20%, and anemia in 60%. Grade 3 non-hematologic toxicity included hyperglycemia and hyponatremia in 20% of the 10 patients. All side effects were manageable and there was no case of treatment-related death. Cisplatin combined with S-1 could be an option for recurrent NSCLC.
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PMID:[Two cases with recurrent non-small cell lung cancer successfully treated with cisplatin and S-1]. 1828 76

S-1 is a novel oral fluorouracil prodrug that plays a role in non-small cell lung cancer (NSCLC). Docetaxel (DTX) is one of the standard agents for relapsed NSCLC. We performed a phase I study of DTX plus S-1 combination therapy as second-line treatment for NSCLC to determine the maximum tolerated dose (MTD) and recommended dose (RD). Patients with recurrent NSCLC, aged 20-74 years with an Eastern Cooperative Oncology Group performance status of 0-1 and measurable lesions, were enrolled. The treatment consisted of four dose levels. The patients received DTX (40-60 mg/m(2) intravenously on day 1) and S-1 (65-80 mg/m(2) orally, daily on days 1-14) for each 21-day cycle. Three to six patients were treated at each dose level with the two drugs, with MTD defined as the dose level at which dose-limiting toxicity (DLT) occurred in 33% of the patients. A total of 17 patients were enrolled. At dose level 4 (DTX, 60 mg/m(2); S-1, 80 mg/m(2)) 3 of 5 patients experienced DLT and this level was regarded as the MTD. Therefore, dose level 3 (DTX, 60 mg/m(2); S-1, 65 mg/m(2)) was selected as the RD for subsequent studies. The DLTs were neutropenia (grade 4) and mucositis (grade 3). The response rate was 5.9% (1 of 17 patients achieved a partial response) and 14 of 17 patients achieved stable disease. This combination regimen showed a tolerable and manageable profile in recurrent NSCLC and therefore warrants further evaluation.
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PMID:Phase I study of docetaxel plus S-1 combination chemotherapy for recurrent non-small cell lung cancer. 2287 Jan 47


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