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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed a study to determine the feasibility of a rapidly alternating administration of cisplatin/vinorelbine (CV) and docetaxel/gemcitabine (DG) in the treatment of advanced non-small-cell lung cancer (NSCLC). Thirty-four patients with NSCLC (6% stage IIIB, 94% stage IV) were enrolled. The initial schema was to give CV on days 1 and 8 followed by DG on days 15 and 22, every 28 days. Granulocyte colony-stimulating factor (G-CSF) was used on days 9-14 and 23-28. Despite dose reductions, this sequence was not feasible. Therefore, the sequence was switched to give DG before CV, cycle duration was extended to 35 days, and G-CSF was given on days 2-7 and 23-28. Neutropenia and thrombocytopenia were dose-limiting toxicities. The recommended doses for phase II studies are docetaxel 75 mg/m2 on day 1, gemcitabine 1000 mg/m2 on days 1 and 8, cisplatin 60 mg/m2 on day 15, and vinorelbine 25 mg/m2 on days 15 and 22, every 35 days with G-CSF 5 microg/kg on days 2-7 and 23-28. However, treatment delays were required in subsequent cycles due to cumulative myelosuppression. A less intensive schedule is recommended for subsequent cycles for further testing. Overall response rate was 29% (95% confidence interval [CI], 14%-45%), and median survival for all patients was 11.8 months. One- and 2-year survival rates were 47% (95% CI, 30%-63%) and 14% (95% CI, 1.4%-40%), respectively. Although initial administration of this regimen was feasible, dose intensity could not be maintained in subsequent cycles due to cumulative myelosuppression. A sequential rather than alternating use of doublet regimens might be more readily feasible and may permit greater maintenance of dose intensity.
Clin Lung Cancer 2002 May
PMID:Phase I study of dose-dense alternating doublets in advanced non-small-cell lung cancer. 1466 35

The purpose of this study was to examine the safety and efficacy of carboplatin/etoposide/paclitaxel in patients with untreated stage IV non-small-cell lung cancer (NSCLC) and extensive small-cell lung cancer (SCLC). Carboplatin was administered intravenously (i.v.) at an area under the curve (AUC) of 6 with etoposide at either 80 or 100 mg/m2 i.v. days 1-3 and paclitaxel at 175 or 200 mg/m2 i.v. over 3 hours along with 5 g/kg of granulocyte colony-stimulating factor subcutaneously on days 4-18, repeated every 3 weeks for 6 courses. Thirty-one patients (five NSCLC and 26 SCLC) entered into this phase I study. The median age was 63 (range, 42 to 74 years), with 24 males and seven females. The recommended dose level for phase II testing was carboplatin AUC = 6, etoposide 80 mg/m2 days 1-3, and paclitaxel 175 mg/m2 over 3 hours. With seven patients at this level, 14% had grade 4 neutropenia, 14% had grade 4 thrombocytopenia, none had grade 2/3 neurotoxicity, and no toxic deaths occurred. One of five (20%) patients with NSCLC responded, and 19 of 22 (86%) evaluable SCLC patients experienced a response to therapy. SCLC patients had a median survival of 10 months. The combination of carboplatin/etoposide/paclitaxel has significant activity with acceptable toxicity in patients with extensive SCLC.
Clin Lung Cancer 2001 Feb
PMID:Carboplatin/etoposide/paclitaxel in the treatment of patients with extensive small-cell lung cancer. 1470 Apr 79

The aim of this phase II trial was to assess the efficacy and tolerability of docetaxel/vinorelbine as second-line therapy. Thirty-two patients with a performance status (PS) of <or= 2 (5 with locally advanced and 27 with metastatic non-small-cell lung cancer [NSCLC]) who were previously treated with platinum-based chemotherapy, were recruited. Docetaxel 75 mg/m2 on day 1 and vinorelbine 20 mg/m2 on days 1 and 5 were administered every 3 weeks with dexamethasone premedication but without prophylactic granulocyte colony-stimulating factor and antibiotics. The overall response rate (intent-to-treat analysis) was 9.5%, including 3 patients with a partial response, 15 (47%) with stable disease, and 9 (28%) with progressive disease. Myelosupression was the limiting toxicity, with 8 episodes of febrile neutropenia and 3 deaths due to sepsis. Median overall survival and progression-free survival were 25 weeks and 13 weeks, respectively. Patients with a PS of 2 (P < 0.02) and elevated lactate dehydrogenase (P < 0.01) had a worse prognosis. Histology of adenocarcinoma appeared to positively influence survival (P = 0.09). Our study confirms that the docetaxel/vinorelbine schedule has activity in NSCLC patients pretreated with platinum-based therapies.
Clin Lung Cancer 2002 Nov
PMID:Phase II study of docetaxel/vinorelbine in patients with non-small-cell-lung cancer previously treated with platinum-based chemotherapy. 1470 66

Assessing the combination of docetaxel with cisplatin or carboplatin was based on their activity as single agents, their nonoverlapping toxicity profiles, and their lack of cross-resistance. Phase I studies of docetaxel in combination with cisplatin established that 75 mg/m2 of each agent could be administered with reasonable safety and appeared to be active in non small-cell lung cancer (NSCLC). We evaluated the docetaxel/cisplatin combination in patients with advanced NSCLC. The response rate was 32%, and the median survival was 11.5 months. Efficacy was comparable to that observed in the Australian and French trials with the same combination. This is now being evaluated further in two large randomized trials for patients with advanced NSCLC and has been incorporated into the combined modality programs for early-stage disease. Carboplatin, devoid of the nephrotoxicity and neurotoxicity associated with the parent cis-platin, was then combined with docetaxel. The recommended dose of docetaxel for further evaluation in combination with carboplatin (AUC=6 mg/mL.min) was 90 mg/m2 with filgrastim support and 80 mg/m2 without filgrastim support. Our phase II trial of the combination of docetaxel and carboplatin in advanced NSCLC demonstrated an overall response rate of 36%; median survival was 13.9 months, and 1-year survival was 52%. Comparable activity has been seen by other investigators, and the regimen is being evaluated in two randomized trials. The combination of docetaxel with either of the two platinum agents has reasonable activity in NSCLC, though the carboplatin/docetaxel doublet appears to have a better therapeutic index.
Clin Lung Cancer 2000 Apr
PMID:Docetaxel in combination with platinum compounds for non small-cell lung cancer. 1472 36

Docetaxel was chosen for study in the combination chemotherapy of advanced non small-cell lung cancer on the basis of its reproducible high single-agent activity, novel mechanism of action, and relative lack of neurotoxicity. Preclinical and clinical data suggested schedule-dependent synergism with vinorelbine. Trials of docetaxel and vinorelbine have explored a variety of schedules. One approach has been to give docetaxel on day 1 of a 3-week cycle with vinorelbine on day 0 or days 1 and 5. Febrile neutropenia and non-neutropenic infections have been dose limiting, and low-dose intensity (8-13 mg/m2/week) of vinorelbine has been achieved. Our phase I study showed that docetaxel 60 mg/m2 and vinorelbine 45 mg/m2 every 2 weeks could be safely given with prophylactic filgrastim. In the ensuing phase II trial, we observed a 51% confirmed response rate in 35 patients (95% confidence interval [CI]: 34-68). With a median follow-up of 12 months, the predicted median and 1-year survivals are 14 months and 60%, respectively. Use of prophylactic filgrastim and the every-2-week schedule of administration allowed for single-agent dose intensity of both drugs to be given. Febrile neutropenia occurred in five patients and 5/384 cycles. Cumulative toxicities of excessive lacrimation, fatigue, and onycholysis were observed. More recently, a weekly schedule of administration for both drugs has been studied. Docetaxel and vinorelbine appear highly active together when given on an every-2-week schedule with prophylactic filgrastim, and the combination may offer one alter-native to cisplatin-based therapy. However, confirmatory phase II and III studies are needed. Certain cumulative toxicities (onycholysis, lacrimation) may limit the duration of therapy. Application of this regimen for a shorter period, such as in induction or postoperative settings, may provide optimal benefit while minimizing toxicity.
Clin Lung Cancer 2000 Apr
PMID:Trials of vinorelbine and docetaxel in the treatment of advanced non small-cell lung cancer. 1472 39

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.
Clin Lung Cancer 2004 Apr
PMID:Second-line chemotherapy for non-small-cell lung cancer: recent data with pemetrexed. 1511 29

Recombinant granulocyte colony-stimulating factor (G-CSF) is used for cancer patients with myelosuppression induced by chemotherapy. G-CSF has been reported to progress tumor growth and angiogenesis, but the precise mechanism of tumor angiogenesis activated by G-CSF has not been fully clarified. N-terminal-mutated recombinant human G-CSF administration increased WBCs and neutrophils in peripheral blood and reduced bone marrow stromal cell-derived factor-1 in mice, indicating its biological relevance. Mice were inoculated with Lewis lung carcinoma cells (LLCs) or KLN205 cells and treated with G-CSF. G-CSF accelerated tumor growth and intratumoral vessel density, while it did not accelerate proliferation of LLCs, KLN205 cells or human umbilical vein endothelial cells in vitro. In the absence of tumors, G-CSF did not increase circulating cells that displayed phenotypic characteristics of endothelial progenitor cells (EPCs). In the presence of tumors, G-CSF increased circulating EPCs. In addition, G-CSF treatment increased immune suppressor and endothelial cell-differentiating Gr1+CD11b+ cells in tumor-bearing mice. We conclude that G-CSF promotes tumor growth by activating tumor angiogenesis via increasing circulating EPCs and Gr1+CD11b+ cells in cancer animal models.
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PMID:Granulocyte colony-stimulating factor promotes tumor angiogenesis via increasing circulating endothelial progenitor cells and Gr1+CD11b+ cells in cancer animal models. 1635 31

Induction chemotherapy may improve clinical outcome of locally advanced non-small cell lung cancer (NSCLC). To further pursue this, the Austrian Association for the Study of Lung Cancer (AASLC) performed a multi-center phase II trial with TIP induction chemotherapy (Taxol 175 mg/m2 over 3h on day 1, ifosfamide 1000 mg/m2 daily on days 1-3, cisplatin 60 mg/m2 on day 1, and prophylactic filgrastim 5 microg/kg daily on days 4-13). Treatment cycles were repeated every 3 weeks for 3 cycles. Then patients were re-staged and selected for local treatment. Forty-seven patients (33 male, 14 female; median age 58 years, range 36-78; 22 cIIIA, 25 cIIIB; 26 adenocarcinomas, 14 squamous cell carcinomas, 4 large cell carcinomas, 3 undifferentiated carcinomas) were included in this trial. Forty-five patients were evaluable for response and toxicity. An overall response rate of 43% (complete remission 4.5% and partial remission 38%) was achieved. Stable disease and progressive disease were seen in 38 and 15% of the patients, respectively. Down-staging occurred in 36% of the patients. The toxicities of the chemotherapy were mild and, in particular, no severe hematotoxicity was observed. Surgery was performed in 24 (51%) patients and resulted in complete tumor resection in 19 patients. Twenty-four patients received thoracic radiotherapy, 10 patients after surgery. Median survival was 10.3 months for the total population, 13.5 months for patients with cIIIA and 10 months for patients with clinical cIIIB. Survival was longer for patients with down-staging as compared to those without (median not reached versus 10 months, p=0.005) and for patients with complete tumor resection as compared to the remaining patients (27 months versus 10 months, p=0.05). In conclusion, the TIP regimen shows activity and good tolerance as induction chemotherapy in patients with locally advanced NSCLC.
Lung Cancer 2006 Oct
PMID:Induction chemotherapy with the TIP regimen (paclitaxel/ifosfamide/cisplatin) in stage III non-small cell lung cancer. 1692 60

The inhibition of topoisomerase I by topotecan results in a compensatory increase in topoisomerase II associated with increased in vitro sensitivity of tumors to etoposide. Maximal synergy has been observed for the sequence of topotecan followed by etoposide. Carboplatin has clinical activity when combined with either of these two agents. These interactions were the pharmacologic rationale for topotecan p.o. days 1-5, carboplatin i.v. day 6, and etoposide p.o. days 6-10. Three successive dose levels were explored: (1) topotecan 2mg/day, carboplatin AUC 5, etoposide 150 mg/day; (2) topotecan 3mg/day, carboplatin AUC 5, etoposide 150 mg/day; and (3) topotecan 3mg/day, carboplatin AUC 5, etoposide 200mg/day. Filgrastim 5 microg/kg/day was injected s.c. days 11-18. Up to 6 cycles were administered every 21 days. Eligible patients had measurable or evaluable, extensive disease, small lung cell lung cancer, no prior chemotherapy, ECOG performance status 0-2, and adequate hematologic, renal, and hepatic function. Follow-up was weekly for CBC. Tumor response was assessed after 2 and 6 cycles. Dose limiting toxicity (DLT) was defined as any of the following in cycle 1: grade 3 or 4 non-hematologic toxicity other than nausea and vomiting, grade 4 neutropenia lasting more than 3 days, neutropenic fever or sepsis, grade 4 thrombocytopenia, or failure to recover neutrophils >or=1500/microl or platelets >or=100,000/microl by day 28. Ten patients were enrolled: median age 62 (range, 50-79); female/male 4/6; and performance status 0/1/2 in 2/7/1. Three patients each were treated on dose levels 1 and 2 without DLT. The first 2 patients entered on dose level 3 had no DLT. The third patient on dose level 3 developed grade 4 neutropenia lasting more than 3 days, neutropenic fever, and grade 4 thrombocytopenia on day 15 of cycle 1. The fourth patient on dose level 3 developed grade 4 thrombocytopenia on day 18 of cycle 1. One patient received only 1 cycle and was not evaluable for response. Seven patients completed 6 cycles: 1 had a complete response and 6 achieved a partial response. The third patient on dose level 3 received 2 cycles and had stable disease, but had to be removed from protocol treatment because of grade 4 neutropenia despite dose reduction in cycle 2. The fourth patient on dose level 3 achieved a partial response, but had to be removed from protocol therapy after cycle 5 because of recurrent grade 4 thrombocytopenia. In conclusion, neutropenia and thrombocytopenia were dose-limiting. The maximum tolerated dose (MTD) is topotecan 3mg/day p.o. days 1-5, carboplatin AUC 5i.v. day 6, and etoposide 150 mg/day p.o. days 6-10 with filgrastim.
Lung Cancer 2006 Dec
PMID:Phase I and pharmacologic study of sequential topotecan-carboplatin-etoposide in patients with extensive stage small cell lung cancer. 1704 3

Giant cell carcinoma (GCC) is a highly aggressive variant of sarcomatoid carcinoma of the lung. To date, however, there have been no reported cases of ovarian carcinoma mainly composed of GCC. Herein is reported the case of a 54-year-old Japanese woman with an undifferentiated ovarian carcinoma producing granulocyte colony-stimulating factor (G-CSF) and an inflammatory cytokine. Histologically, the tumor was composed of cohesive nests or discohesive pleomorphic mononucleated or multinucleated tumor giant cells, accompanied by inflammatory cell infiltration and emperipolesis. Immunohistochemically, the tumor cells were focally positive for epithelial membrane antigen and cytokeratin 7. Clinically, after the initial surgery, the tumor had rapid regrowth along with the production of G-CSF and an inflammatory cytokine. Adjuvant chemotherapy was administered but induced severe heart failure and severe neutropenia, probably due to the presence of hypercytokinemia and excess G-CSF. Upon the appearance of these fatal side-effects the chemotherapy was immediately discontinued and replaced with radiotherapy. The recognition of this type of ovarian tumor is important for clinical management, because adjuvant chemotherapy is the standard treatment for clinical management of epithelial ovarian cancer.
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PMID:Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung. 1832 18


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