Survival of Hypercapnic Patients with COPD and Obesity Hypoventilation Syndrome Treated with High Intensity Non Invasive Ventilation in the Daily Routine Care.

BACKGROUND: Home ventilation is an effective treatment option for obesity hypoventilation syndrome (OHS). This therapy is still controversial for stable chronic obstructive pulmonary disease (COPD). A recent study showed reduced mortality for COPD patients receiving home ventilation with high inflation pressures and back-up respiratory rates [so called High Intensity non-invasive ventilation (NIV)]. OBJECTIVE: The purpose of this study is whether High Intensity NIV applied in the routine care of COPD and OHS patients can lead to CO2 reduction and survival data comparable to data from controlled studies. METHOD: In this prospective non interventional study fifty-one patients with COPD (FEV1 0.95l, corr. 32.8%) and 34 patients with OHS (VC 1.74l, corr. 50.7%) with chronic hypercapnic respiratory failure, who were treated with NIV were followed up for four years. RESULTS: Elevated CO2 values before NIV in COPD patients (8.6kPa), and in OHS patients (8.3kPa), could be lowered significantly to the upper normal range (COPD: 5.9kPa; OHS: 5.85kPa). The one-, two-, and three-year survival rates for COPD patients were 83%, 73%, and 55%, respectively. The one-, two-, and three-year survival rates for OHS patients were 85%, 72%, and 68%, respectively. CONCLUSION: High intensity NIV within routine care is effective in reducing blood CO2 levels in COPD- and in OHS- related chronic respiratory insufficiency. The survival rates obtained here are comparable to data from controlled clinical trials on COPD.

A Prospective Phase I/II Study: Combination Chemotherapy with Docetaxel and Pemetrexed as Second-Line Treatment in Patients with Stage IIIB/IV Non-Small Cell Lung Cancer.

INTRODUCTION: Two standard single-agent chemotherapy treatments (docetaxel and pemetrexed) were combined in this trial and administered as second-line treatment in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and feasibility of combining docetaxel with pemetrexed. METHODS: Six patients were enrolled between August 2007 and March 2009 with stage IIIB/IV NSCLC. The dose-escalation model included a pemetrexed infusion on day 1 of 200-300 mg/m(2) followed by infusion of docetaxel on days 1, 8 and 15 at doses from 20 to 30 mg/m(2). Primary study endpoints included efficacy and safety variables, also progression-free, overall and 1-year survival and time to progression. RESULTS: The study was abandoned due to adverse effects defined in the protocol. The major toxicities were all of grade 3 and included fatigue, stomatitis/mucositis, diarrhea and in one case, an episode of febrile neutropenia. Two patients died during the study, but not as a direct result of the treatment. CONCLUSIONS: We recommend that docetaxel or pemetrexed monotherapies should continue to be considered the standard second-line chemotherapy treatment against NSCLC. The results of this study warrant no further investigation into this particular combination treatment due to the severe toxicity effects encountered.

Six-minute walk distance and dyspnoea scores to assess the course of COPD exacerbation in elderly patients.

INTRODUCTION: While the severity of stable chronic obstructive pulmonary disease (COPD) has been defined in a valid and relevant prognostic manner, parameters that describe the course of COPD exacerbations are not yet established. Physical performance and dyspnoea are of prognostic relevance in stable COPD. The issue investigated was to assess the course of COPD exacerbations to find parameters that describe this situation better. METHODS: In 82 hospitalised patients with acute exacerbation of COPD who responded to intensified medical treatment (age 67.3 ± 9.5 years; forced expiratory volume in 1 s 1.0l, 40% predicted), we measured the 6-min walk distance and the visual analogue scale dyspnoea scores before the start of treatment, prior to discharge and after a 4-week stable period. Additionally, the conventional clinical parameters of COPD and quality of life were documented. RESULTS: The 6-min walk distance was significantly increased from 97 ± 114 m to 290 ± 106 m. After 4 weeks of outpatient treatment in clinically stable patients, the 6-min walk distance fell non-significantly to 270 ± 120 m. The increment in walk distance fell significantly with advancing severity of COPD: from 112 ± 68 m for grade I and II to 56 ± 88 m for grade IV. Resting as well as exertional dyspnoea scores were significantly reduced (resting dyspnoea from 4 to 2 and exertional dyspnoea from 8 to 6). CONCLUSION: We were able to demonstrate that 6-min walk test and dyspnoea scores, but not pulmonary function test, are suitable parameters to assess the course of COPD exacerbations.

Influence of NaCl 0.9% Infusion during Plasmapheresis on IgG Content in Plasma.

BACKGROUND: The aim of this study was to evaluate the influence of an infusion of NaCl 0.9% 500 ml during preparatory plasmapheresis or apheresis on the immunoglobulin G (IgG) content in separated plasma. METHODS: 32 donors of plasma were studied in a crossover design after informed consent on one day without NaCl 0.9% 500 ml during apheresis and on another day with infusion of NaCl 0.9% 500 ml during apheresis. Infusion of NaCl 0.9% 500 ml was given step by step in divided doses after each cycle through the harness set of the Haemonetics® plasma collecting system 2 (PCS2). Concentrations of IgG in serum and in plasma were measured by an immunoturbidimetric assay. Percentages of IgG concentrations in plasma were calculated by dividing the IgG concentration in plasma by the mean serum IgG concentrations (x 100). RESULTS: Without infusion of NaCl 0.9% 500 ml, the mean percentage of IgG in separated plasma was 85.5 ± 2.3% while it was 80.5 ± 3.4% when NaCl 0.9% 500 ml was given. The difference between the two samples was statistically highly significant (p < 0.001). CONCLUSIONS: We conclude that the gradual infusion of NaCl 0.9% 500 ml during apheresis causes a statistically highly significant difference of IgG content in separated plasma.

A relative survival model for clustered responses.

Relative Survival is the ratio of the overall survival of a group of patients to the expected survival for a demographically similar group. It is commonly used in disease registries to estimate the effect of a particular disease when the true cause of death is not reliably known. Regression models for relative survival have been described and we extend these models to allow for clustered responses by embedding them into the class of Generalized linear mixed models (GLMM). The method is motivated and demonstrated by a data set from the HALLUCA study, an epidemiological study which investigated provision of medical care to lung cancer patients in the region of Halle in the eastern part of Germany.

Randomized, multicenter, open-label phase II study of gemcitabine plus single-dose versus split-dose carboplatin in the treatment of patients with advanced-stage non-small-cell lung cancer.

BACKGROUND: Gemcitabine/carboplatin is a convenient and effective treatment for advanced-stage non-small-cell lung cancer (NSCLC), but modification of the schedule to diminish thrombocytopenia is worthwhile. PATIENTS AND METHODS: One hundred fifty-eight chemotherapy-naive patients with stage IIIB/IV NSCLC were randomized from 15 centers in Germany to receive gemcitabine 1250 mg/m(2) on days 1 and 8 plus carboplatin area under the curve 5 on day 1 (arm A) or carboplatin area under the curve 2.5 on days 1 and 8 (arm B), every 21 days for 4 cycles. RESULTS: The 2 arms (A vs. B) were well balanced with regard to patient baseline characteristics: stage IV 72.5% versus 69%, median Eastern Cooperative Oncology Group performance status 1 versus 1. The incidence of grade 3/4 hematologic toxicity was as follows (percentage of patients in arm A vs. B): leukopenia 37.5% versus 27% (P = 0.075), granulocytopenia 36% versus 36%, and thrombocytopenia 51% versus 35% (P = 0.017). Nonhematologic toxicity was modest and comparable with both schedules. The overall response rate was 46% versus 36% (P = 0.12), and 24% versus 42% had stable disease. Median progression-free survival (5.8 months vs. 6.1 months) and overall survival (11.7 months vs. 10.7 months) were not significantly different between arms A and B. CONCLUSION: Splitting the dose of carboplatin between days 1 and 8 on the same days as gemcitabine results in a significantly decreased incidence of severe thrombocytopenia, without compromising the activity of the combination.

Multicenter randomized trial for stage IIIB/IV non-small-cell lung cancer using every-3-week versus weekly paclitaxel/carboplatin.

PURPOSE: The combination of paclitaxel with carboplatin is effective in advanced-stage non-small cell lung cancer (NSCLC). This phase III study was designed to compare the efficacy and tolerability of a weekly versus an every-3-week schedule in the first-line treatment of advanced-stage NSCLC. PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to receive paclitaxel 100 mg/m2 and carboplatin at an area under the curve of 2 once weekly for 6-8 weeks (arm A) or paclitaxel 200 mg/m2 and carboplatin at an area under the curve of 6 on day 1 every 21 days (arm B). RESULTS: A total of 883 patients received >or= 1 chemotherapy cycle and were included in the results. The objective response rates observed (complete response plus partial response) were 38% for arm A and 33% for arm B. Median times to progression and median survival times were 6.1 months and 8.9 months in arm A and 7.2 months and 9.5 months in arm B, respectively. There were no significant differences between treatment arms. The chemotherapy was well tolerated in both schedules. However, grade 3/4 sensory neuropathy occurred more frequently with the every-3-week schedule (9.1% vs. 4.4%), whereas grade 3/4 diarrhea occurred more frequently with the weekly schedule (4.2% vs. 1.1%). CONCLUSION: In terms of response and survival, paclitaxel/carboplatin administered once weekly is comparable with the every-3-week schedule. Toxicity differences should be considered when choosing the appropriate schedule for the individual.

Phase III study of second-line chemotherapy for advanced non-small-cell lung cancer with weekly compared with 3-weekly docetaxel.

PURPOSE: A phase III study to determine whether a weekly docetaxel schedule improves the therapeutic index compared with the classic 3-weekly schedule. PATIENTS AND METHODS: Patients with stage IIIB-IV non-small-cell lung cancer (NSCLC) were randomly assigned to docetaxel 75 mg/m2 on day 1 every 3 weeks (3-weekly) and 35 mg/m2 on days 1, 8, and 15 (weekly) for < or = eight cycles. End points included survival (primary), toxicity, and response. RESULTS: Of 215 patients enrolled, 208 (103 in the 3-weekly arm and 105 in the weekly arm) were assessable for response. At baseline, 24.5% of patients (51 out of 208) had received prior paclitaxel therapy and 43.3% of patients (90 out of 208) had been progression-free for more than 3 months after first-line therapy. After 12 months' follow-up, median survival was 6.3 months (95% CI, 4.68 to 7.84 months) with 3-weekly docetaxel and 9.2 months (95% CI, 5.83 to 12.59 months) with weekly docetaxel (P = .07) after a median of four (range, one to eight) and two (range, one to eight) treatment cycles, respectively. Overall, response rates were 12.6% v 10.5% with 3-weekly versus weekly docetaxel. Significantly fewer patients reported grade 3 to 4 toxicities with weekly docetaxel versus 3-weekly docetaxel (P < or = .05). There were significantly lower rates of grade 3 to 4 anemia (P < or = .05), leucopenia (P < .0001), and neutropenia (P < or = .001) with weekly versus 3-weekly treatment. No grade 3 to 4 thrombocytopenia or mucositis was reported. CONCLUSION: Weekly docetaxel 35 mg/m2 demonstrated similar efficacy and better tolerability than standard 3-weekly docetaxel 75 mg/m2 and can be recommended as a feasible alternative second-line treatment option for patients with advanced NSCLC.

Phase II trial of gemcitabine/irinotecan in refractory or relapsed small-cell lung cancer.

BACKGROUND: Gemcitabine and irinotecan have shown a broad range of activity in solid tumors, including small-cell lung cancer (SCLC), with a synergistic effect on SCLC cell lines. The objective of this phase II trial was to evaluate the activity of gemcitabine/irinotecan in patients with relapsed SCLC. PATIENTS AND METHODS: Thirty-five patients (15 with refractory disease and 20 with sensitive disease) who had experienced treatment failure with 1 previous chemotherapy regimen were recruited. Treatment consisted of gemcitabine 1,000 mg/m(2) and irinotecan 100 mg/m(2) on days 1 and 8 of a 21-day cycle for a maximum of 6 cycles. Eligibility criteria included an Eastern Cooperative Oncology Group performance status of 0-2, adequate organ function, and signed informed consent. RESULTS: All 35 patients were assessable for response, survival, and toxicity. Best objective responses exhibited were as follows: complete response in 2 patients (6%), partial response in 4 (11%; 95% confidence interval [CI], 21%-61%), stable disease in 7 (20%; 95% CI, 9%-45%), and progressive disease in 22 (63%; 95% CI, 17%-57%). Median time to disease progression was 3.4 months and median survival was 5.8 months. The 1-year survival rate was 34%. Toxicity was mainly hematologic. Grade 3/4 nausea and vomiting occurred in 9% of patients, neuropathy occurred in 2.8%, and diarrhea occurred in 14.3%. Survival was not significantly different for patients with refractory versus sensitive disease. CONCLUSION: The combination of gemcitabine/irinotecan was shown to be active as second-line chemotherapy, especially in patients with refractory disease.

Clinical benefit in NSCLC: advanced-stage patients require symptom-improving palliation. Experiences from the 'Iressa' expanded access program.

BACKGROUND: The molecular genesis of lung cancer and its treatment remain hot spots of medical research because of the high mortality rates especially associated with non-small-cell lung cancer (NSCLC). New agents are required. The epidermal growth factor receptor (EGFR) pathway inhibitor gefitinib (Iressa) has been the first approved drug for NSCLC within this new therapeutic class. PATIENTS AND METHODS: The anti-tumor activity of gefitinib in a monocentric and prospective case series of 72 patients with refractory NSCLC is analyzed. Patients who had histologically confirmed NSCLC with one or more previous chemotherapies were eligible for enrollment. Patients received 250 mg gefitinib orally once daily for at least 28 days. RESULTS: An 8% response rate (PR) and an additional 42% rate of disease stabilizations (SD) have been found in our patient collective. The median survival of all patients was 8.6 weeks (95% CI 5.9-11.2). Comparing responders, patients with stable disease, and progressive patients it becomes evident that patients sensitive to gefitinib get a clinical benefit in terms of palliation and overall survival. Adenocarcinoma histology and former nicotine abstention seem to favor sensitivity to gefitinib. CTC grade 3/4 toxicities were observed in only one patient in form of skin reactions. Mild toxicities (CTC grade 1/2) were diarrhea, conjunctivitis and elevation of transaminases. CONCLUSION: These prospective data suggest an activity of gefitinib in pre-treated NSCLC patients without relevant toxicities. They are in agreement with other published data.

Survival of patients in clinical stages I-IIIb of non-small-cell lung cancer treated with radiation therapy alone. Results of a population-based study in Southern Saxony-Anhalt.

BACKGROUND AND PURPOSE: Up to now, evidence about survival of patients with non-small-cell lung cancer treated with radiation therapy alone is only available from clinical studies. The authors analyzed survival experience depending on several prognostic factors from a population-based cancer registry and compared this to survival data from the literature. PATIENTS AND METHODS: Between April 1996 and September 1999, 1,696 patients with lung cancer were recruited by the Halle Lung Cancer (HALLUCA) Study. 1,183 patients were diagnosed as having non-small-cell lung cancer, and 188 in clinical stages I-IIIb (15.9%) were treated with radiation therapy alone. RESULTS: The median survival time of all patients was 10.2 months, the 2-year overall survival rate amounted to 15.8%. Besides tumor stage, radiation dose was found to be a statistically significant prognostic factor for survival in univariate analysis. The median survival time was 4.2 months for 66 patients treated with < 50 Gy, 10.7 months for 80 patients treated with 50 to < 60 Gy, and 18.9 months for 42 patients treated with >/= 60 Gy; the corresponding 2-year overall survival rates were 8.7%, 13.4%, und 35.2%. The significant influence of dose persisted even after adjustment for different confounders in a Cox regression model. CONCLUSION: Patients treated with 50 to < 60 Gy under a potentially curative therapeutic regimen had a significantly lower survival, compared to patients treated with >/= 60 Gy. In terms of quality assurance, the large proportion of patients treated with radiation doses below the curative range of >/= 60 Gy was unexpected.

A multicenter phase II study of gemcitabine and oxaliplatin for malignant pleural mesothelioma.

We conducted a phase II multicenter trial to evaluate the activity of combined gemcitabine and oxaliplatin in malignant pleural mesothelioma. Twenty-five patients were recruited between May 1999 and December 2001 and received gemcitabine 1000 mg/m2 intravenously over 30 minutes and oxaliplatin 80 mg/m2 intravenously over 3 hours on days 1 and 8 of a 21-day cycle for a maximum of 6 cycles. Eligibility criteria included an Eastern Cooperative Oncology Group performance status of 0-2 and no prior chemotherapy. Best objective responses achieved were as follows: partial response, 10 patients (40%, 95% CI, 21%-61%); stable disease, 6 patients (24%, 95% CI, 9%-45%); and progressive disease, 9 patients (36%, 95% CI, 18%-57%). Median time to disease progression was 7 months, and median survival was 13 months. One-year survival was 60% (95% CI, 31%-72%). There were 2 deaths from disease progression. Toxicity was mainly hematologic. Grade 3/4 nausea and vomiting occurred in 8% of patients, neuropathy occurred in 8% of patients, and diarrhea occurred in 4% of patients. The combination of gemcitabine and oxaliplatin was shown to be active in malignant pleural mesothelioma and to exhibit tolerable toxicity in an outpatient setting.