Publications by authors named "Ulrich Gatzemeier"

49 Publications

Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial.

Target Oncol 2015 Jun 9;10(2):255-65. Epub 2014 Sep 9.

LungenClinic Grosshansdorf, Woehrendamm 80, 22927, Grosshansdorf, Germany,

The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) investigated the efficacy and safety of weekly and every 2 weeks cetuximab maintenance therapy in this setting. Patients were treated with platinum-based chemotherapy plus cetuximab, and those progression-free after four to six cycles were randomized to every 2 weeks (500 mg/m(2)) or weekly (250 mg/m(2)) cetuximab maintenance. Randomization was stratified for tumor histology and response status. The primary endpoint for a regimen would be reached if the lower boundary of the 95 % confidence interval (CI) for the 1-year survival rate exceeded 55 %. A planned 480 patients were to be randomized. However, enrollment was curtailed following a negative opinion from the European Medicines Agency with regard to the use of cetuximab in this setting. After combination therapy, 311/583 (53.3 %) patients without progression were randomized to maintenance therapy: 157 to every 2 weeks cetuximab and 154 to weekly cetuximab. Baseline characteristics were balanced between these groups and exposure to cetuximab was similar. The 1-year survival rate was 62.8 % (95 % CI, 54.7-70.0) for every 2 weeks cetuximab and 64.4 % (95 % CI, 56.2-71.4) for weekly cetuximab. Safety profiles were similar, manageable, and in line with expectations. Therefore, in patients with advanced NSCLC who were progression-free after four to six cycles of first-line chemotherapy plus cetuximab, weekly and every 2 weeks cetuximab maintenance therapy were associated with similar survival outcomes.
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http://dx.doi.org/10.1007/s11523-014-0336-7DOI Listing
June 2015

Efficacy and safety of bronchoscopic laser therapy in patients with tracheal and bronchial obstruction: a retrospective single institution report.

Clin Respir J 2012 Apr 27;6(2):67-71. Epub 2011 Jun 27.

Department of Thoracic Oncology, Grosshansdorf Hospital, Grosshansdorf, Germany.

Purpose: The aim of this retrospective study is to present data efficacy and safety of bronchoscopic laser therapy in patients with tracheal and bronchial obstruction.

Patients And Methods: From February 2004 to April 2010, our electronic database was searched for all patients who had undergone bronchoscopic laser therapy. We collected data on age, gender, performance status, diagnosis leading to bronchoscopic laser treatment, number of procedures per patient, efficacy by means of extend of recanalisation and symptom improvement, additional interventions and procedure-related complications.

Results: Two hundred fifty-six procedures were performed in 121 patients. 17% of obstructions were localised in the trachea, 57% in main bronchi and 26% in lobar bronchi including right intermedius bronchus. The sum of complete and partial recanalisation reached 95%, 80% and 68%, respectively. 26% of interventions in lobar bronchi were undertaken to treat haemoptysis which could be controlled in all cases. Moderate bleeding occurred in 6%; severe bleeding in 1%. Cardiac arrhythmias were seen in 2%. We observed one treatment-related death (overall mortality 0.4%).

Conclusion: Bronchoscopic laser therapy is a generally safe and effective method to regain airway patency in cases with tracheal or bronchial obstruction and to treat haemoptysis. We observed clinical improvement in terms of reduced dyspnea or controlled haemoptysis in 93% of our patients.
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http://dx.doi.org/10.1111/j.1752-699X.2011.00247.xDOI Listing
April 2012

Molecular biomarkers in non-small-cell lung cancer: a retrospective analysis of data from the phase 3 FLEX study.

Lancet Oncol 2011 Aug 22;12(8):795-805. Epub 2011 Jul 22.

HOPE directorate, St James's Hospital, Dublin, Ireland.

Background: Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting.

Methods: Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened for KRAS codon 12 and 13 and EGFR kinase domain mutations with PCR-based assays. In FFPE tissue sections, EGFR copy number was assessed by dual-colour fluorescence in-situ hybridisation and PTEN expression by immunohistochemistry. Treatment outcome was investigated according to biomarker status in all available samples from patients in the intention-to-treat population. The primary endpoint in the FLEX study was overall survival. The FLEX study, which is ongoing but not recruiting participants, is registered with ClinicalTrials.gov, number NCT00148798.

Findings: KRAS mutations were detected in 75 of 395 (19%) tumours and activating EGFR mutations in 64 of 436 (15%). EGFR copy number was scored as increased in 102 of 279 (37%) tumours and PTEN expression as negative in 107 of 303 (35%). Comparisons of treatment outcome between the two groups (chemotherapy plus cetuximab vs chemotherapy alone) according to biomarker status provided no indication that these biomarkers were of predictive value. Activating EGFR mutations were identified as indicators of good prognosis, with patients in both treatment groups whose tumours carried such mutations having improved survival compared with those whose tumours did not (chemotherapy plus cetuximab: median 17·5 months [95% CI 11·7-23·4] vs 8·5 months [7·1-10·8], hazard ratio [HR] 0·52 [0·32-0·84], p=0·0063; chemotherapy alone: 23·8 months [15·2-not reached] vs 10·0 months [8·7-11·0], HR 0·35 [0·21-0·59], p<0·0001). Expression of PTEN seemed to be a potential indicator of good prognosis, with patients whose tumours expressed PTEN having improved survival compared with those whose tumours did not, although this finding was not significant (chemotherapy plus cetuximab: median 11·4 months [8·6-13·6] vs 6·8 months [5·9-12·7], HR 0·80 [0·55-1·16], p=0·24; chemotherapy alone: 11·0 months [9·2-12·6] vs 9·3 months [7·6-11·9], HR 0·77 [0·54-1·10], p=0·16).

Interpretation: The efficacy of chemotherapy plus cetuximab in the first-line treatment of advanced NSCLC seems to be independent of each of the biomarkers assessed.

Funding: Merck KGaA.
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http://dx.doi.org/10.1016/S1470-2045(11)70189-9DOI Listing
August 2011

Long-term safety and tolerability of sorafenib in patients with advanced non-small-cell lung cancer: a case-based review.

Clin Lung Cancer 2011 Jul 28;12(4):212-7. Epub 2011 Apr 28.

Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

Background: Sorafenib, a small-molecule inhibitor of multiple kinases involved in tumor growth and progression, is approved for the treatment of advanced renal-cell carcinoma and advanced hepatocellular carcinoma. Encouraging activity and good tolerability of daily oral sorafenib, either as a single agent or in combination with gefitinib, have been demonstrated in phase I-II trials in patients with advanced non-small-cell lung cancer (NSCLC). Currently, minimal data are available describing the long-term safety and tolerability of sorafenib in patients with NSCLC.

Materials And Methods: We describe a series of 12 patients with advanced NSCLC (derived from 1 phase I and 2 phase II trials) who achieved long-term (ie, > 12 months) disease control and continued to receive sorafenib alone or in combination with gefitinib beyond the end of the study in which they were enrolled.

Results: The safety profile of sorafenib administered on a long-term basis did not differ significantly from that seen previously in the shorter term. The majority of adverse events (AEs) were Grade 1-2 in severity. Five of the 12 patients experienced no ≥ Grade 3 AEs. There was no evidence of increased frequency or severity of AEs over time, or of late AEs, and no patient in this series discontinued study treatment because of AEs.

Conclusion: In patients with advanced NSCLC who achieve a prolonged response or stable disease with sorafenib given as a single agent or as part of a combination regimen, sorafenib treatment could be continued until disease progression without major long-term safety or tolerability problems.
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http://dx.doi.org/10.1016/j.cllc.2011.03.021DOI Listing
July 2011

First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy: a subgroup analysis of data from the FLEX phase 3 study.

Lancet Oncol 2011 Jan 17;12(1):30-7. Epub 2010 Dec 17.

Department of Thoracic Oncology, Hospital Grosshansdorf, Hamburg, Germany.

Background: The randomised phase 3 First-Line Erbitux in Lung Cancer (FLEX) study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival compared with chemotherapy alone in the first-line treatment of advanced non-small-cell lung cancer (NSCLC). The main cetuximab-related side-effect was acne-like rash. Here, we assessed the association of this acne-like rash with clinical benefit.

Methods: We did a subgroup analysis of patients in the FLEX study, which enrolled patients with advanced NSCLC whose tumours expressed epidermal growth factor receptor. Our landmark analysis assessed if the development of acne-like rash in the first 21 days of treatment (first-cycle rash) was associated with clinical outcome, on the basis of patients in the intention-to-treat population alive on day 21. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798.

Findings: 518 patients in the chemotherapy plus cetuximab group-290 of whom had first-cycle rash-and 540 patients in the chemotherapy alone group were alive on day 21. Patients in the chemotherapy plus cetuximab group with first-cycle rash had significantly prolonged overall survival compared with patients in the same treatment group without first-cycle rash (median 15·0 months [95% CI 12·8-16·4] vs 8·8 months [7·6-11·1]; hazard ratio [HR] 0·631 [0·515-0·774]; p<0·0001). Corresponding significant associations were also noted for progression-free survival (median 5·4 months [5·2-5·7] vs 4·3 months [4·1-5·3]; HR 0·741 [0·607-0·905]; p=0·0031) and response (rate 44·8% [39·0-50·8] vs 32·0% [26·0-38·5]; odds ratio 1·703 [1·186-2·448]; p=0·0039). Overall survival for patients without first-cycle rash was similar to that of patients that received chemotherapy alone (median 8·8 months [7·6-11·1] vs 10·3 months [9·6-11·3]; HR 1·085 [0·910-1·293]; p=0·36). The significant overall survival benefit for patients with first-cycle rash versus without was seen in all histology subgroups: adenocarcinoma (median 16·9 months, [14·1-20·6] vs 9·3 months [7·7-13·2]; HR 0·614 [0·453-0·832]; p=0·0015), squamous-cell carcinoma (median 13·2 months [10·6-16·0] vs 8·1 months [6·7-12·6]; HR 0·659 [0·472-0·921]; p=0·014), and carcinomas of other histology (median 12·6 months [9·2-16·4] vs 6·9 months [5·2-11·0]; HR 0·616 [0·392-0·966]; p=0·033).

Interpretation: First-cycle rash was associated with a better outcome in patients with advanced NSCLC who received cisplatin and vinorelbine plus cetuximab as a first-line treatment. First-cycle rash might be a surrogate clinical marker that could be used to tailor cetuximab treatment for advanced NSCLC to those patients who would be most likely to derive a significant benefit.
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http://dx.doi.org/10.1016/S1470-2045(10)70278-3DOI Listing
January 2011

Lactate dehydrogenase as prognostic factor in limited and extensive disease stage small cell lung cancer - a retrospective single institution analysis.

Respir Med 2010 Dec 16;104(12):1937-42. Epub 2010 Aug 16.

Dept. of Thoracic Oncology, Grosshansdorf Hospital, Woehrendamm 80, Grosshansdorf, Germany.

Purpose: The aim of this retrospective study is to present data on clinical significance of lactate dehydrogenase (LDH) serum levels in an unselected contemporary patient population with small cell lung cancer (SCLC) in limited disease (LD) and extensive disease stage (ED).

Patients And Methods: From June 2004 to June 2008, our electronic database including all in-patient and out-patient contacts was searched for patients with newly diagnosed LD and ED SCLC. 397 cases were identified. We collected data on patient characteristics including clinical performance status and LDH serum levels, metastatic sites, efficacy of first line chemotherapy and survival.

Results: In both limited and extensive disease SCLC, elevated LDH serum levels resulted in significantly shorter median survival. The effect was most pronounced if levels were 300 U/l or higher. In patients with limited disease and normal LDH levels, median survival was 18.0 months. If LDH was higher than 300 U/l, overall survival was reduced to 12 months. In cases with extensive disease, overall survival was significantly lower in patients with elevated LDH serum levels with an additional reduction in overall survival in patients with LDH levels above 300 U/l. (7.0 vs. 12.0 months, p = <0.001). Multivariate Cox regression analyses revealed LDH levels to be an independent predictor of mortality after adjustment for age and Performance Status in LD and ED SCLC (HR 1.003, p = 0.017; HR 1.001, p = 0.002 respectively). However, categorizing LDH levels revealed no significant difference in LD SCLC.

Conclusion: In our contemporary comprehensive patient population, LDH is proved to be a strong, independent predictive factor of median survival in patients with LD and ED SCLC.
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http://dx.doi.org/10.1016/j.rmed.2010.07.013DOI Listing
December 2010

Characteristics, treatment patterns and outcomes of patients with small cell lung cancer--a retrospective single institution analysis.

Lung Cancer 2011 Mar 8;71(3):363-6. Epub 2010 Jul 8.

Dept. of Thoracic Oncology, Grosshansdorf Hospital, Grosshansdorf, Germany.

Purpose: The aim of this retrospective study is to present data on patient characteristics, treatment patterns, and treatment results in an unselected contemporary patient population with small cell lung cancer (SCLC) in limited disease (LD) and extensive disease stage (ED).

Patients And Methods: From June 2004 to December 2008, our electronic database including all in-patient and out-patient contacts was searched for patients with newly diagnosed lung cancer. 397 patients were found having SCLC. We collected data on patient characteristics, chemotherapy, side effects, response on treatment and survival.

Results: 39% of all patients had LD SCLC. Median age was 63 years. The response rate (RR) reached 76%. Stable disease was the result of first line therapy in 16%. Consecutive thoracic radiotherapy was given in 72%. Additional prophylactic cranial irradiation (PCI) was administered to 33%. 43% received second line therapy. Median survival was 18.8 months. In 61% of cases, ED SCLC was diagnosed. Median age was 61 years. Main metastatic sites were liver, bone, brain and adrenal glands. RR was 69%. Stable disease and progressive disease were the result of first line chemotherapy both in 12%. 15% received palliative cranial irradiation, 3% PCI. 51% were treated with second line therapy. Median survival reached 10.6 months.

Conclusion: We provide a comprehensive analysis of a contemporary patient population. Treatment patterns and survival data fit well in the context of current international trials on more selected patients. Multivariate analyses confirmed extend of disease, performance status and LDH serum levels as independent prognostic factors for survival. Age and gender reached no statistical significance.
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http://dx.doi.org/10.1016/j.lungcan.2010.06.003DOI Listing
March 2011

[Local and systemic therapy of non-small cell lung carcinoma (NSCLC)].

Onkologie 2010 14;33 Suppl 5. Epub 2010 May 14.

Onkologischer Schwerpunkt, Zentrum für Pneumologie und Thoraxchirurgie, Krankenhaus Grosshansdorf, München, Deutschland.

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http://dx.doi.org/10.1159/000313970DOI Listing
October 2010

Sunitinib in combination with gemcitabine plus cisplatin for advanced non-small cell lung cancer: a phase I dose-escalation study.

Lung Cancer 2010 Nov 25;70(2):180-7. Epub 2010 Feb 25.

Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf 22927, Germany.

Purpose: To determine the maximum tolerated dose (MTD) of sunitinib plus gemcitabine/cisplatin for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Safety, pharmacokinetics, and antitumor activities were evaluated.

Methods: Patients ≥18 years with Eastern Cooperative Oncology Group performance status 0/1 and stage IIIB/IV NSCLC were included in this open-label, multicenter, dose-escalation phase I study. Treatment was administered in 3-week cycles: oral sunitinib 37.5 or 50mg/day intermittently (Schedule 2/1: 2 weeks on treatment, 1 week off treatment) or 25mg continuous daily dosing (CDD) schedule with intravenous infusions of gemcitabine (1000 or 1250 mg/m(2) days 1, 8) and cisplatin (80 mg/m(2) day 1).

Results: A total of 28 evaluable patients were assigned to four dose levels. Most adverse events (AEs) on the Schedule 2/1 MTD were mild to moderate. Dose delays due to myelosuppression occurred on both schedules, limiting treatment to a median of four cycles. Four of 18 evaluable patients (22%) on Schedule 2/1 and 1 of 6 patients (17%) on the CDD schedule had confirmed partial responses.

Conclusions: The MTD was identified as sunitinib 37.5mg (Schedule 2/1), gemcitabine 1250 mg/m(2), and cisplatin 80 mg/m(2), with most AEs being mild to moderate. However, frequent dose delays due to myelosuppression occurred. There was evidence of antitumor activity with this combination.
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http://dx.doi.org/10.1016/j.lungcan.2010.01.016DOI Listing
November 2010

Incidence of febrile neutropenia and myelotoxicity of chemotherapy: a meta-analysis of biosimilar G-CSF studies in breast cancer, lung cancer, and non-Hodgkin's lymphoma.

Onkologie 2009 Oct 14;32(10):599-604. Epub 2009 Sep 14.

Klinik I für Innere Medizin, Klinikum der Universität zu Köln, Cologne, Germany.

Background: The aim of this meta-analysis of 3 clinical studies, conducted with breast cancer, lung cancer, and non-Hodgkin's lymphoma patients, was to compare a new granulocyte colony-stimulating factor (G-CSF) biosimilar, XM02, with filgrastim in terms of its prophylactic effect on the development of febrile neutropenia (FN) during the first chemotherapy cycle in relation to the myelotoxic potency of the applied chemotherapy regimen.

Patients And Methods: Overall, 608 patients (363 under XM02 and 245 under filgrastim) were included in the meta-analysis. The majority of patients were allocated to the chemotherapy categories docetaxel-doxorubicin (45.4%) and cyclophosphamide-hydroxy daunomycin (adriamycin)-oncovin (vincristine)-prednisolone (CHOP)/platinum(Pt)-vinorelbine or Pt-vinblastine/ Pt-etoposide (43.1%); another 11.5% were allocated to the category Pt-gemcitabine/Pt-docetaxel or Pt-paclitaxel.

Results: FN in the XM02 and filgrastim groups was reported for 12.1 and 12.5% of patients, respectively, under docetaxeldoxorubicin, for 13.5 and 11.9% under CHOP/Pt-vinorelbine or Pt-vinblastine/Pt-etoposide, and for 15.6 and 12.0% under Pt-gemcitabine/Pt-docetaxel or Pt-paclitaxel.

Conclusions: The incidence of FN in the first cycle of chemotherapy under primary G-CSF prophylaxis is low (in the range of 12-16%) and not directly correlated with the myelotoxic potency of the applied chemotherapy regimen. XM02 demonstrated to be non-inferior to filgrastim regarding the incidence of FN, irrespective of the myelotoxicity of the chemotherapy regimen.
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http://dx.doi.org/10.1159/000232580DOI Listing
October 2009

Phase II, multicenter, uncontrolled trial of single-agent sorafenib in patients with relapsed or refractory, advanced non-small-cell lung cancer.

J Clin Oncol 2009 Sep 3;27(26):4274-80. Epub 2009 Aug 3.

The M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 432, Houston, TX 77030-4009, USA.

Purpose: Sorafenib is an oral multikinase inhibitor that targets the Ras/Raf/MEK/ERK mitogenic signaling pathway and the angiogenic receptor tyrosine kinases, vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor beta. We evaluated the antitumor response and tolerability of sorafenib in patients with relapsed or refractory, advanced non-small-cell lung cancer (NSCLC), most of whom had received prior platinum-based chemotherapy.

Patients And Methods: This was a phase II, single-arm, multicenter study. Patients with relapsed or refractory advanced NSCLC received sorafenib 400 mg orally twice daily until tumor progression or an unacceptable drug-related toxicity occurred. The primary objective was to measure response rate.

Results: Of 54 patients enrolled, 52 received sorafenib. The predominant histologies were adenocarcinoma (54%) and squamous cell carcinoma (31%). No complete or partial responses were observed. Stable disease (SD) was achieved in 30 (59%) of the 51 patients who were evaluable for efficacy. Four patients with SD developed tumor cavitation. Median progression-free survival (PFS) was 2.7 months, and median overall survival was 6.7 months. Patients with SD had a median PFS of 5.5 months. Major grades 3 to 4, treatment-related toxicities included hand-foot skin reaction (10%), hypertension (4%), fatigue (2%), and diarrhea (2%). Nine patients died within a 30-day period after discontinuing sorafenib, and one patient experienced pulmonary hemorrhage that was considered drug related. CONCLUSION Continuous treatment with sorafenib 400 mg twice daily was associated with disease stabilization in patients with advanced NSCLC. The broad activity of sorafenib and its acceptable toxicity profile suggest that additional investigation of sorafenib as therapy for patients with NSCLC is warranted.
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http://dx.doi.org/10.1200/JCO.2009.22.0541DOI Listing
September 2009

Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial.

Lancet 2009 May;373(9674):1525-31

Medical University of Vienna, Vienna, Austria.

Background: Use of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has the potential to increase survival in patients with advanced non-small-cell lung cancer. We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer.

Methods: In a multinational, multicentre, open-label, phase III trial, chemotherapy-naive patients (>or=18 years) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy. Chemotherapy was cisplatin 80 mg/m(2) intravenous infusion on day 1, and vinorelbine 25 mg/m(2) intravenous infusion on days 1 and 8 of every 3-week cycle) for up to six cycles. Cetuximab-at a starting dose of 400 mg/m(2) intravenous infusion over 2 h on day 1, and from day 8 onwards at 250 mg/m(2) over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred. The primary endpoint was overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00148798.

Findings: Between October, 2004, and January, 2006, 1125 patients were randomly assigned to chemotherapy plus cetuximab (n=557) or chemotherapy alone (n=568). Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group (median 11.3 months vs 10.1 months; hazard ratio for death 0.871 [95% CI 0.762-0.996]; p=0.044). The main cetuximab-related adverse event was acne-like rash (57 [10%] of 548, grade 3).

Interpretation: Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer.

Funding: Merck KGaA.
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http://dx.doi.org/10.1016/S0140-6736(09)60569-9DOI Listing
May 2009

XM02, the first biosimilar G-CSF, is safe and effective in reducing the duration of severe neutropenia and incidence of febrile neutropenia in patients with small cell or non-small cell lung cancer receiving platinum-based chemotherapy.

J Thorac Oncol 2009 Jun;4(6):736-40

Center of Pneumology and Thoracic Surgery, Department of Thoracic Surgery, Grosshansdorf, Germany.

Background: Recombinant granulocyte colony-stimulating factors such as Neupogen are used to treat chemotherapy-induced neutropenia. The aim of the study was to show that a new granulocyte colony-stimulating factor, XM02, is as safe and effective as Neupogen in the treatment of chemotherapy-induced neutropenia in patients with small cell or non-small cell lung cancer.

Patients And Methods: A total of 240 patients receiving platinum-based chemotherapy were randomized in cycle 1 to treatment with daily injections (subcutaneous 5 microg/kg/d) of XM02 (n = 160) or Filgrastim Neupogen (n = 80) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received XM02.

Results: The mean duration of severe neutropenia was 0.5 and 0.3 days in cycle 1 for XM02 and Filgrastim, respectively. In the analysis of covariance for duration of severe neutropenia in cycle 1, the estimated treatment difference "XM02 minus Filgrastim" was 0.157 days, with 95% confidence level (-0.114 days, 0.428 days), which was included in the prespecified equivalence range (-1, 1). There was no statistically significant difference of the end point incidence of febrile neutropenia in cycle 1 between XM02 and Filgrastim (p = 0.2347). The adverse event profile was similar between XM02 and Filgrastim.

Conclusion: XM02 demonstrated similar efficacy and safety profile as the reference medication Filgrastim in cycle 1. In conclusion, treatment with XM02 is beneficial in ameliorating severe neutropenia and febrile neutropenia in lung cancer patients receiving myelosuppressive chemotherapy. XM02 is safe and well tolerated in the doses applied in this study.
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http://dx.doi.org/10.1097/JTO.0b013e3181a52964DOI Listing
June 2009

Multicenter randomized open-label phase III study comparing efficacy, safety, and tolerability of conventional carboplatin plus etoposide versus dose-intensified carboplatin plus etoposide plus lenograstim in small-cell lung cancer in "extensive disease" stage.

Am J Clin Oncol 2009 Feb;32(1):61-4

Department of Oncology, Krankenhaus Grosshansdorf, Grosshansdorf, Schleswig-Holstein, Germany.

Background: The combination of carboplatin and etoposide (CE) is one of the most effective regimens in the treatment of small-cell lung cancer (SCLC). The aim of this study was to investigate whether dose-intensified CE with the supplementation of granulocyte-colony-stimulating factor (G-CSF) is more effective than conventional CE in terms of survival with acceptable toxicity.

Methods: In a 2-arm multicentric prospective open label study, adult patients with SCLC in "extensive disease" stage were randomized either to conventional CE (carboplatin AUC 5 on day 1 IV and etoposide 140 mg/m IV on days 1-3, q28 days) or to dose-intensified therapy (carboplatin AUC 5 on day 1 IV and etoposide 190 mg/m days 1-3 IV with lenograstim 263 microg subcutaneously on days 4-13, q21 days). Primary end point was overall survival; secondary endpoints were toxicity, quality of life, and disease-free survival.

Results: Seventy-nine patients were included. Thirty-seven received conventional CE and 42 received the dose-intensified regimen. Median survival in the conventional group and the dose-intensified group were 11.2 months [confidence interval (CI) 9.1-15.2] and 11.7 months (CI 8.8-14.7), respectively. Progression-free survival was 6.7 (CI 5.8-7.5) and 7.4 months (CI 6.2-9.0), respectively. There was no statistically significant difference between these groups. Grade 3/4 neutropenia occurred in 69.4% in the conventional arm versus 37.5% in the dose-intensified group (P = 0.009).

Conclusion: Dose-intense CE with GM-CSF support can be administered safely but does not prolong overall or progression-free survival compared with standard therapy.
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http://dx.doi.org/10.1097/COC.0b013e31817be954DOI Listing
February 2009

[Foreword].

Onkologie 2008 ;31 Suppl 3

Onkologischer Schwerpunkt, Zentrum fur Pneumologie und Thoraxchirurgie, Krankenhaus Grosshansdorf, Deutschland.

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http://dx.doi.org/10.1159/000128573DOI Listing
July 2008

A phase II pharmacodynamic study of erlotinib in patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy.

Clin Cancer Res 2008 Jun;14(12):3867-74

Medical Oncology Service and Pathology Service, Vall d'Hebron University Hospital, Barcelona, Spain.

Purpose: To examine potential markers of clinical benefit and the effects of erlotinib on the epidermal growth factor receptor (EGFR) signaling pathway in advanced non-small cell lung cancer patients refractory to platinum-based chemotherapy.

Experimental Design: Patients were given erlotinib (150 mg/d). Tumor biopsies were done immediately before treatment and in a subgroup of patients after 6 weeks' treatment.

Results: Of 73 evaluable patients, 7 (10%) had partial response and 28 (38%) had stable disease. In 53 patients with baseline tumor samples, no relationship was observed between pretreatment levels of EGFR, phosphorylated (p)-EGFR, p-AKT, p-mitogen-activated protein kinase (MAPK), or p27 and clinical benefit (i.e., response, or stable disease >/=12 weeks). Tumors from 15 of 57 patients had high EGFR gene copy number, assessed using fluorescence in situ hybridization (FISH positive), 10 of whom had clinical benefit, compared with 5 of 42 FISH-negative patients. FISH-positive patients had longer median progression-free [137 versus 43 days, P = 0.002; hazard ratio (HR), 0.37] and overall (226 versus 106 days, P = 0.267; HR, 0.70) survival than FISH-negative patients. In paired biopsy samples from 14 patients, p-EGFR (P = 0.002), p-MAPK (P = 0.001), and Ki-67 (P = 0.025) levels were significantly reduced after 6 weeks' treatment. Apoptosis was significantly increased in patients with clinical benefit (P = 0.029), and may be a marker of clinical benefit.

Conclusion: In this study, EGFR FISH-positive status was associated with improved outcome after erlotinib therapy. Erlotinib led to reduced levels of p-EGFR, p-MAPK, and Ki-67, and stimulated apoptosis in tumor samples from patients with clinical benefit.
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http://dx.doi.org/10.1158/1078-0432.CCR-07-5186DOI Listing
June 2008

Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer.

J Clin Oncol 2008 Jul 27;26(21):3543-51. Epub 2008 May 27.

University of Torino, Department of Clinical and Biological Sciences, S. Luigi Hospital, Regione Gonzole, 10, Orbassano (Torino), Italy.

Purpose: Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting.

Patients And Methods: This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m(2) on day 1 and gemcitabine 1,250 mg/m(2) on days 1 and 8 (n = 863) or cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 (n = 862) every 3 weeks for up to six cycles.

Results: Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P
Conclusion: In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.
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http://dx.doi.org/10.1200/JCO.2007.15.0375DOI Listing
July 2008

Phase III trial comparing carboplatin, paclitaxel, and bexarotene with carboplatin and paclitaxel in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT II.

J Clin Oncol 2008 Apr;26(11):1879-85

Department of Thoracic/Head & Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 432, Houston, TX 77030, USA.

Purpose: The purpose of this study was to determine whether addition of the synthetic rexinoid bexarotene (Targretin; Eisai Inc, Woodcliff Lake, NJ) to standard first-line carboplatin and paclitaxel therapy provides additional survival benefit in patients with advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Patients with stage IIIB disease with pleural effusion, or stage IV NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1, were randomly assigned to bexarotene 400 mg/m(2)/d combined with carboplatin and paclitaxel, or assigned to carboplatin and paclitaxel alone. Bexarotene patients also received lipid-lowering agents on or before day 1. The primary efficacy end point was overall survival; secondary efficacy and supportive analyses were also conducted.

Results: A total of 612 patients (306 per arm) were enrolled onto the study. In the intent-to-treat population, no significant difference in survival occurred between the two arms. However, a subpopulation (approximately 40%) of bexarotene-treated patients who experienced National Cancer Institute grade 3/4 hypertriglyceridemia had significantly longer median survival than control patients (12.4 v 9.2 months; log-rank, P = .014). Bexarotene-treated patients with grade 3/4 hypertriglyceridemia who received the most benefit included those who were male, were smokers, experienced 6-month prior weight loss >or= 5%, and had stage IV disease. The incidence and severity of most adverse events were similar between arms, although hyperlipidemia, neutropenia, fatigue, leukopenia, arthralgia, and diarrhea were more frequent in the bexarotene arm.

Conclusion: Although the addition of bexarotene to chemotherapy did not improve survival in the overall study population, occurrence of high-grade hypertriglyceridemia in bexarotene-treated patients strongly correlated with increased survival, suggesting that bexarotene may benefit a segment of first-line NSCLC patients.
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http://dx.doi.org/10.1200/JCO.2007.12.2689DOI Listing
April 2008

Diagnostics and staging procedures in non-small cell lung cancer - is less more?

Clin Respir J 2008 Apr;2(2):67-73

Krankenhaus Grosshansdorf, Onkologischer Schwerpunkt, Woehrendamm, Grosshansdorf Schleswig-Holstein, Germany.

Introduction: Non-small cell lung cancer (NSCLC) is a common cancer with approximately 85% of patients dying of the disease. The only chance for cure is in the early stages, when surgery or definite chemoradiotherapy can be performed. Diagnosis and staging of lung cancer can sometimes be difficult, particularly because the intrathoracic structures are not easy to reach.

Objective: This review discusses the diagnosis and staging of lung cancer.

Results: When performing lung cancer diagnostics, both invasive and noninvasive procedures, such as computed tomogram of the chest, bronchoscopy and abdominal ultrasound, are mandatory. Suspected mediastinal involvement should be differentiated: bulky disease, contralateral or high mediastinal nodes need further clarification by endoscopic ultrasound, endobronchial ultrasound or mediastinoscopy. In opposition to current guidelines, in all other cases, surgery should be performed. Positron emission tomography will gain even more importance when becoming widely accessible and might replace other imaging techniques in the future. In case of advanced disease, staging should be limited to those examinations with impact on symptom control.

Conclusion: The diagnosis and staging of lung cancer should involve both invasive and noninvasive diagnostic procedures. In the case of advanced disease, staging should be limited to those examinations with impact on symptom control, whereas early stages call for rapid and thorough diagnosis.
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http://dx.doi.org/10.1111/j.1752-699X.2008.00049.xDOI Listing
April 2008

[Non-small cell lung cancer - diagnostics and stage-adapted therapy].

Med Klin (Munich) 2007 Dec;102(12):981-8; quiz 989-90

Onkologischer Schwerpunkt, Krankenhaus Grosshansdorf.

Non-small cell lung cancer is a common disease. Adeno- and squamous-cell type are the most frequent subtypes, the former with rising incidence. The clinical picture is nonspecific until late in the course of the disease. The most important diagnostic tools are chest X-ray, computed tomogram of the chest, and bronchoscopy. Additional tests often used for staging are abdominal ultrasound, computed tomography of the abdomen, bone scintigraphy, and magnetic resonance imaging of the head. Positron emission tomography is of rising importance. Therapy is guided by stage. Stage I disease is a domain of surgery, in stage II combined with adjuvant chemotherapy. In stage III, multimodality treatment, mostly chemoradiotherapy, is indicated. Stage IV disease is treated with palliative chemotherapy. Newer, so-called targeted therapies are more and more implemented into therapy. There are three substances approved for second-line therapy with response rates of just under 10%.
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http://dx.doi.org/10.1007/s00063-007-1122-4DOI Listing
December 2007

[Foreign body aspiration mimicking lung cancer].

Med Klin (Munich) 2007 Oct;102(10):859-60

Krankenhaus Grosshansdorf, Zentrum für Pneumologie und Thoraxchirurgie, Grosshansdorf.

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http://dx.doi.org/10.1007/s00063-007-1106-4DOI Listing
October 2007

Oral vinorelbine in the treatment of non-small cell lung cancer: rationale and implications for patient management.

Drugs 2007 ;67(10):1403-10

New York Lung Cancer Alliance, New York, NY 10024-5129, USA.

Vinorelbine is an established treatment for advanced non-small cell lung cancer (NSCLC), both as a single agent and in combination chemotherapy. Recently, an oral form of this agent has been developed. Before accepting an established agent in a different administration form, rigorous testing is required to answer such questions as reliable bioavailability, continued safety and preservation of efficacy. In addition, an oral agent must provide patient convenience and acceptance, while being an economically sound approach. Oral vinorelbine was found to have acceptable and reliable pharmacokinetic profiles at clinically relevant dosage levels. Oral vinorelbine was found to have approximately 40% bioavailability; thus, a dose of 80 mg/m(2) orally is the equivalent of 30 mg/m(2) intravenously, and 60 mg/m(2) orally is the equivalent of 25 mg/m(2) intravenously. Studies also concluded a lack of food effect on the administration of oral vinorelbine. In addition, no drug-drug interactions were found with a variety of commonly used antineoplastic agents.Vinorelbine, either orally or intravenously, has been investigated in randomised phase II trials as a single agent and in combination with cisplatin or carboplatin in patients with NSCLC. In general, response and survival results with oral vinorelbine appeared similar to the intravenous agent. Adverse-effect profiles were also similar for the two formulations. Clearly, the issue of venous irritation does not exist with oral vinorelbine; however, nausea and vomiting were more frequent when vinorelbine was administered orally compared with intravenously when no planned antiemetic therapy is given.
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http://dx.doi.org/10.2165/00003495-200767100-00003DOI Listing
August 2007

Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial.

J Clin Oncol 2007 Apr;25(12):1545-52

Zentrum Fur Pneumologie Und Thoraxchirurgie, Krankenhaus D LVA, Germany.

Purpose: Erlotinib is a potent inhibitor of the epidermal growth factor receptor tyrosine kinase, with single-agent antitumor activity. Preclinically, erlotinib enhanced the cytotoxicity of chemotherapy. This phase III, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of erlotinib in combination with cisplatin and gemcitabine as first-line treatment for advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Patients received erlotinib (150 mg/d) or placebo, combined with up to six 21-day cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1). The primary end point was overall survival (OS). Secondary end points included time to disease progression (TTP), response rate (RR), duration of response, and quality of life (QoL).

Results: A total of 1,172 patients were enrolled. Baseline demographic and disease characteristics were well balanced. There were no differences in OS (hazard ratio, 1.06; median, 43 v 44.1 weeks for erlotinib and placebo groups, respectively), TTP, RR, or QoL between treatment arms. In a small group of patients who had never smoked, OS and progression-free survival were increased in the erlotinib group; no other subgroups were found more likely to benefit. Erlotinib with chemotherapy was generally well tolerated; incidence of adverse events was similar between arms, except for an increase in rash and diarrhea with erlotinib (generally mild).

Conclusion: Erlotinib with concurrent cisplatin and gemcitabine showed no survival benefit compared with chemotherapy alone in patients with chemotherapy-naïve advanced NSCLC.
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http://dx.doi.org/10.1200/JCO.2005.05.1474DOI Listing
April 2007

[Pillnitz interdisciplinary discussion--summary].

Onkologie 2006 Sep 6;29 Suppl 2. Epub 2006 Sep 6.

Zentrum für Pneumologie und Thoraxchirurgie, Onkologischer Schwerpunkt, Krankenhaus Grosshansdorf, Deutschland.

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http://dx.doi.org/10.1159/000094946DOI Listing
September 2006

Gefitinib monotherapy in chemotherapy-naive patients with inoperable stage III/IV non-small-cell lung cancer.

Clin Lung Cancer 2006 May;7(6):406-11

Department of Thoracic Oncology, Hospital Grobhansdorf, Germany.

Background: Gefitinib is an orally active epidermal growth factor receptor tyrosine kinase inhibitor with activity in previously treated patients with advanced-stage non-small-cell lung cancer (NSCLC). However, little is known of its activity as monotherapy in chemotherapy-naive patients. This phase II study (1839IL/0456) evaluated first-line gefitinib in patients with advanced-stage NSCLC.

Patients And Methods: Eligible patients with proven inoperable stage III/IV NSCLC, no previous chemotherapy, and a performance status of 0-2 received gefitinib 250 mg per day until disease progression. Patient reevaluation was performed by radiography and computed tomography at regular intervals.

Results: Fifty-eight of 59 patients were available for analysis. Response rate (complete plus partial responses) was 5% (3 of 58 patients); 40% (23 of 58 patients) exhibited stable disease (overall disease control rate, 45% [26 of 58 patients]). Median progression-free survival was 7 weeks, and median overall survival was 29 weeks. All responders were women and/or nonsmokers with adenocarcinoma or bronchoalveolar carcinoma. Gefitinib treatment was well tolerated; skin toxicities occurred in 71% of patients, including severe skin toxicities in 2 patients, and mild to moderate diarrhea occurred in 50% of patients.

Conclusion: Gefitinib monotherapy has some efficacy in chemotherapy-naive patients with advanced-stage or metastatic NSCLC. However, activity seems to be limited to particular patient groups.
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http://dx.doi.org/10.3816/clc.2006.n.025DOI Listing
May 2006

Efficient palliation in patients with small-cell lung cancer by a combination of paclitaxel, etoposide and carboplatin: quality of life and 6-years'-follow-up results from a randomised phase III trial.

Lung Cancer 2006 Jul 19;53(1):67-75. Epub 2006 May 19.

Department of Thoracic Oncology, Hospital Grosshansdorf, Wöhrendamm 80, D-22927 Grosshansdorf, Germany.

Purpose: Based on the promising activity of paclitaxel in small-cell lung cancer (SCLC) we conducted a randomized phase III trial to evaluate whether a combination of paclitaxel, carboplatin and etoposide phosphate (TEC) improves survival and time to progression as well as tolerability and quality of life (QoL) compared to a regimen of carboplatin, etoposide phosphate and vincristine (CEV) in SCLC patients.

Patients And Methods: Six hundred and fourteen patients with stages I-IV SCLC were randomly assigned between January 1998 and December 1999 to both treatment arms. All patients were evaluated for response rate, survival, side effects and quality of life with overall survival (OS) serving as primary endpoint. A final analysis was done after a six-year follow-up. Survival curves were estimated using Kaplan-Meier curves and tested with the log-rank test. Quality of life data were assessed in using the EORTC QLQ-C30 questionnaire and evaluated by calculating and comparing the mean scores as well as applying longitudinal techniques.

Results: Six hundred and eight patients were evaluable for efficacy and toxicity. The long-term follow-up confirms the significant survival benefit for the paclitaxel, etoposide, carboplatin (TEC) regimen with a median OS of 12.5 months compared to 11.7 months for the CEV arm (HR, 1.21; 95% CI, 1.02-1.43; P=.030). The 5-year survival rates were 14% for the experimental versus 6 % for the CEV arm. Significant survival prolongation was also observed in the subgroup of patients with stage IV disease (HR, 1.27; 95% CI, 1.00-1.60; P=.047). The previously reported clinical benefit in form of an overall reduction of grade 3/4 toxicity was backed by the results of the comprehensive QoL analysis we report hereby. TEC significantly improves the relevant QoL parameters like global overall QoL or physical functioning.

Conclusion: When administered in combination with etoposide and carboplatin, paclitaxel is able to offer in SCLC patients with extensive disease a survival benefit without additional toxicities, but with gains in patient-reported quality of life. In terms of efficient palliative care, TEC might be seen as an alternative to standard cisplatin plus etoposide in patients requesting a powerful palliative regimen not compromising any survival benefit.
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http://dx.doi.org/10.1016/j.lungcan.2006.04.001DOI Listing
July 2006

[EGFR/HER1 inhibition: an example of new targeted therapies in non-small cell lung cancer].

Med Klin (Munich) 2005 Dec;100(12):785-93

Onkologischer Schwerpunkt, Krankenhaus Grosshansdorf, Grosshansdorf.

Background: Lung cancer is one of the most common forms of cancer in western industrialized countries. Patients with advanced non-small cell lung cancer (NSCLC) have a poor prognosis and suffer many tumor-associated symptoms. Unfortunately, approximately 70% of patients with NSCLC present themselves with advanced poor-prognosis stage III and IV disease. In advanced disease, treatment is palliative and symptom-oriented. New less Adenotoxic drugs are urgently needed. One of the targets of new agents is the human epidermal growth factor receptor (EGFR/HER1), and agents targeting this receptor include erlotinib, gefitinib and cetuximab.

Clinical Studies: Erlotinib, gefitinib and cetuximab have been investigated in different clinical studies and provided objective responses and symptom relief. A benefit in survival could only be observed in second- and third-line therapy with erlotinib. All new agents have been generally well tolerated. Erlotinib was recently approved in the USA and Europe for second- and third-line treatment of patients with locally advanced or metastatic NSCLC.

Conclusion: Anti-EGFR has shown promising antitumor activity in NSCLC with a mild toxicity profile. However, some clinical issues such as screening for potentially responsive patients and optimal combination with other drugs should be the aim of future studies.
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http://dx.doi.org/10.1007/s00063-005-1130-1DOI Listing
December 2005

Randomized multicenter phase II study of gemcitabine versus docetaxel as first-line therapy with second-line crossover in advanced-stage non-small-cell lung cancer.

Clin Lung Cancer 2005 Nov;7(3):208-14

Heidelberg University Medical Center Mannheim, Mannheim, Germany.

Background: A randomized phase II study was performed to determine whether single-agent gemcitabine or docetaxel with the introduction of the opposite agent in case of disease progression (ie, in the second-line setting) is feasible and effective in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: The doses were 1,000 mg/m2 for gemcitabine and 35 mg/m2 for docetaxel, each given on days 1, 8, and 15 every 4 weeks. After a planned interim analysis, the docetaxel/gemcitabine arm (ie, docetaxel followed by gemcitabine) was closed after enrollment of 49 patients because of poor predefined feasibility. A total of 98 patients were recruited to the gemcitabine/docetaxel arm (ie, gemcitabine followed by docetaxel).

Results: Quality of life remained near baseline levels during the administration of 6 cycles of gemcitabine/docetaxel chemotherapy, whereas it deteriorated after 2 cycles of docetaxel/gemcitabine. Toxicity was comparable between arms. Median times to progression were 4.3 months and 2.2 months with gemcitabine/docetaxel and docetaxel/gemcitabine, respectively, and median overall survival times were 9 months (gemcitabine/docetaxel) and 5 months (docetaxel/gemcitabine; P=0.029, Wilcoxon rank-sum test).

Conclusion: These results indicate that first-line gemcitabine followed by second-line weekly docetaxel is feasible, with promising survival in patients with advanced NSCLC.
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http://dx.doi.org/10.3816/clc.2005.n.038DOI Listing
November 2005

EGFR tyrosine kinase inhibitors in non-small cell lung cancer: report of a 3-year compassionate use experience with gefitinib in stage IIIB/IV outpatients.

Onkologie 2005 Dec 1;28(12):623-7. Epub 2005 Dec 1.

Krankenhaus Grosshansdorf, Zentrum für Thoraxchirurgie, Grosshansdorf, Germany.

Background: Since March 2002, 240 patients with advanced stage IIIB/IV non-small cell lung cancer (NSCLC) have been treated inside a compassionate use program with oral gefitinib (250 mg o.d.).

Patients And Methods: Within a 36-month observation period, 32 patients who showed either partial remission or confirmed disease stabilization for at least 3 months, were retrospectively analyzed.

Results: Our reported 4% overall response rate matches with literature data for an unselected patient population. The median progression-free survival (PFS) was 9 months, the median overall survival (OS) since detection of advanced disease was 21 months. Interestingly, no relevant differences in PFS were observed for chemo-naive and second/third-line patients, whereas a reduced benefit in terms of response rate, PFS and OS was found for forth-line patients. 12 patients survived for at least 2 years since manifestation of their advanced disease. A slight benefit regarding cough and performance status conservation was observed. Mild to modest skin reactions and diarrhea were the adverse events reported most often. Grade 3 toxicities were rarely observed.

Conclusions: The retrospective evaluation of therapy results from compassionate use patients helps clinicians to better evaluate new drugs in practice. EGFR tyrosine kinase (TK) inhibitors require ongoing intensive evaluation to optimize their clinical use in NSCLC.
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http://dx.doi.org/10.1159/000088931DOI Listing
December 2005