Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study.

BACKGROUND: In this superiority study, pemetrexed was compared with erlotinib in pre-treated patients with metastatic non-small cell lung cancer (NSCLC). METHODS: Patients with stage IIIB/IV NSCLC who progressed after first-line or second-line treatment were randomized to receive either pemetrexed or erlotinib. In total, 21.7% of patients in the pemetrexed arm and 23.5% of patients in the erlotinib arm had squamous cell histology, and treatment was third line in 39.2% and 46.4% of patients, respectively. The primary study endpoint was time to tumor progression (TTP). Epidermal growth factor receptor/v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (EGFR/KRAS) mutation status also was investigated. RESULTS: There was no difference in terms of the TTP (P = .195), the objective response rate (P = .469), or overall survival (P = .986) between the 2 treatment arms. In patients who had squamous cell histology, erlotinib resulted in a superior TTP compared with pemetrexed (4.1 months vs 2.5 months, respectively; P = .006). The incidence of grade 3 and 4 neutropenia, thrombocytopenia, and asthenia was significantly higher in the pemetrexed arm, whereas the incidence of grade 3 and 4 skin rash was higher in the erlotinib arm. CONCLUSIONS: Both pemetrexed and erlotinib had comparable efficacy in pre-treated patients with metastatic NSCLC, and the current results indicated that genotyping of tumor cells may have an important effect on treatment efficacy.

Six minute walking test and carbon monoxide diffusing capacity for non-small cell lung cancer: easy performed tests in every day practice.

BACKGROUND: Several studies have demonstrated that reduced lung function is a significant risk factor for lung cancer and increased surgical risk in patients with operable stages of lung cancer. The aim of the study was to perform pulmonary function tests and investigate which is a favorable respiratory function test for overall survival between lung cancer stages. METHODS: Lung function tests were performed to lung cancer patients with non-small cell lung cancer of stage I, II, III and IV (241 patients in total). They had the last follow-up consecutively between December 2006 and July 2008. The staging was decided according to the sixth edition of TNM classification of NSCLC. The Forced Expiratory Volume in 1sec (FEV1), Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) were measured according to American Thoracic Society/European Respiratory Society guidelines. The 6 Minute Walking Test (6MWT) was measured according to the American Thoracic Society. RESULTS: There was a significant association of the DLCO upon diagnosis and overall survival for stage II (P<0.007) and IV (P<0.003). Furthermore, there was a significant association between 6MWT and overall survival for stage III (P<0.001) and stage IV (P<0.010). CONCLUSIONS: The significance for each lung function test is different among the stages of NSCLC. DLCO and 6MWT upon admission are the most valuable prognostic factors for overall survival of NSCLC.

Clinical differences between influenza A (H1N1) virus and respiratory infection between the two waves in 2009 and 2010.

BACKGROUND: The purpose of the present retrospective study was to examine the clinical differences between patients hospitalized with H1N1 virus and those hospitalized with nonvirus respiratory tract infection in 2009 and 2010. METHODS: Adult patient data were collected from three tertiary hospital centers. Real-time reverse transcriptase polymerase chain reaction testing was used to confirm the diagnosis. We included 106 H1N1-positive patients (52 from 2009 and 54 from 2010). These data were compared with those from 108 patients with H1N1-negative respiratory tract infection (51 patients from 2009 and 57 from 2010). RESULTS: In 2009, the mean age was 36.4 years for H1N1-positive patients versus 46.4 years for H1N1-negative patients, and mean body mass index (BMI) was 26.4 kg/m(2) patients and 28.1 kg/m(2), respectively. In 2009, seven patients required intubation, six of whom were H1N1-positive. In 2010, the mean age was 43.8 years for H1N1-positive patients versus 60.2 years for H1N1-negative patients, and mean BMI was 32.3 kg/m(2) and 26.9 kg/m(2), respectively. In 2010, six patients required intubation, three of whom were H1N1-positive. Abnormal chest x-ray findings were found significantly more frequently in H1N1-negative patients than in H1N1-positive patients. CONCLUSION: In comparison with 2009, H1N1-positive patients in 2010 were older, were more likely to be obese, and had more severe clinical and laboratory perturbations. However, this did not affect their outcomes. H1N1-negative patients were older in comparison with those who were H1N1-positive, and had more severe clinical and laboratory perturbations.

A multicenter randomized phase II study of the irinotecan/gemcitabine doublet versus irinotecan monotherapy in previously treated patients with extensive stage small-cell lung cancer.

OBJECTIVES: To compare the efficacy and safety profile of irinotecan (I) versus the combination of irinotecan/gemcitabine (IG) as second-line treatment of patients with extensive stage small-cell lung cancer (SCLC). TREATMENT: Patients with SCLC who have received at least one chemotherapy regimen were randomized to receive either the IG regimen (gemcitabine 1000mg/m(2) intravenous (i.v.) on days 1 and 8 and irinotecan 300mg/m(2) i.v. on day 8) or I monotherapy (300mg/m(2) i.v. on day 1) both every 3 weeks. RESULTS: Thirty-eight patients were enrolled in the IG and 31 in the I arm. Due to slow accrual an early closure of the study was decided. Response rate was significantly higher in the IG than in I arm (23.7% vs. 0%; p=0.004). The median time to progression (TTP) was 3.9 months (range: 0.5-14.5 months; 95% CI: 1.4-6.6) and 1.7 months (range: 0.5-9.9 months; 95% CI: 1.2-2.3) (p=0.010) for the IG and I arms, respectively. There was no difference in terms of median overall survival between the two arms (6.8 months and 4.6 months for the IG and I arm, respectively). The most frequent toxicities were grade III/IV neutropenia and grade III/IV diarrhea. CONCLUSIONS: Although the IG regimen seems to be more active than the I monotherapy, the premature closure of the study prevents the drawing of definitive conclusions.

Combination of vinorelbine plus gemcitabine in previously treated patients with small cell lung cancer: a multicentre phase II study.

PURPOSE: To evaluate the efficacy and toxicity of the gemcitabine plus vinorelbine combination in pretreated patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Thirty-five pretreated patients (median age 59 years, PS: 0--1 in 97% and 2 in 3%) were treated with gemcitabine (1100 mg/m(2)) and vinorelbine (25mg/m(2)) on d1 and d8 every 3 weeks. Seven (20%) patients were treated with two prior regimens and 20 (57%) were refractory to front-line chemotherapy. RESULTS: In an intention-to-treat analysis two (6%) partial responses (PR) were observed with a duration of 5.6 and 11.1 months. Stable disease (SD) was documented in 8 (23%) patients and progressive disease (PD) in 25 (71%). The overall median survival was 4.5 and the 6 months survival rate was 42.6%. Grades 3--4 neutropenia and thrombocytopenia were observed in 25 and 14% of the patients, respectively. Non-hematological toxicity consisted of grade 2 neurotoxicity occurring in 14% of the patients and grades 2--3 fatigue in 17%. Febrile neutropenia was observed in three (8.6%) patients and one of them died from sepsis. CONCLUSION: The combination of gemcitabine plus vinorelbine cannot be considered as an effective salvage treatment in pretreated patients with SCLC.

Hormonal profile in patients with congestive heart failure.

BACKGROUND: Recent progress has been made in the understanding of the cellular and molecular mechanisms of growth hormone action and of its effects on cardiac tissue. The aim of this study was to measure growth hormone concentrations, along with various other hormones, in patients with stable chronic congestive heart failure due to idiopathic dilated cardiomyopathy. METHODS: The study included 23 ambulatory men, 51.2+/-9.3 years of age, on standard medical therapy for heart failure due to idiopathic dilated cardiomyopathy. All patients underwent clinical and laboratory evaluations, including echocardiogram, radionuclide ventriculography, right heart catheterization, coronary angiography, and right ventricular endomyocardial biopsy. Serum or plasma concentrations of growth, thyroid, sex and adrenal hormones were measured in all patients and compared with those found in 20 age-matched healthy men. RESULTS: Growth hormone, insulin-like growth factor I, and free testosterone values in patients with idiopathic dilated cardiomyopathy and heart failure were 0.37+/-0.2 ng/ml, 123.7+/-50 ng/ml and 48.6+/-23.8 pmol/l, respectively, versus 0.5+/-0.4 ng/ml (P<0.01), 236.3+/-66.4 ng/ml (P<0.001) and 105+/-17 pmol/l (P<0.01), respectively, in the healthy age-matched individuals. All other hormone concentrations were comparable in both groups. CONCLUSIONS: Chronic heart failure due to idiopathic dilated cardiomyopathy is associated with a significant decrease in growth hormone, insulin-like growth factor I, and testosterone concentrations, probably due to chronic disease.

Lowering of furosemide dosage after clinical stabilization in patients with congestive heart failure.

OBJECTIVES: This study was performed to examine the safety of reducing the long-term doses of furosemide administered to patients with congestive heart failure (CHF) stabilized on a standard medical treatment. METHODS AND RESULTS: Twenty-nine patients with advanced CHF were treated with enalapril, digoxin, nitrates, and furosemide, as needed to alleviate their symptoms, and remained clinically stable for at least 3 months on those doses. Subsequently, the daily dose of furosemide was reduced to 1/3 of the previous dose, while the concomitant therapy was unchanged. All patients underwent a thorough clinical evaluation and right-heart catheterization before and 2 months after the furosemide dose reduction. After the treatment optimization the NYHA functional class decreased from 2.3 +/- 0.6 to 1.4 +/- 0.6 (p = 0.000), and the left ventricular ejection fraction increased from 22 +/- 10% to 32 +/- 13%, (p = 0.000). Clinical and haemodynamic evaluation before and after 2 months of treatment with lower furosemide doses showed that 24 of the 29 patients (83%) remained in a stable NYHA functional class and maintained a stable haemodynamic status. In the remaining 5 patients (17%), mean NYHA functional class increased from 1.8 +/- 0.4 to 2.4 +/- 0.6 (p = 0.07), accompanied by a significant increase of the right and left ventricular filling pressures from 4.2 +/- 2.7 to 9.0 +/- 3.0 mm Hg, p = 0.018 and from 8.6 +/- 3.0 to 19.8 +/- 3.6 mm Hg, p = 0.017, respectively. These 5 patients returned to a stable clinical status upon resumption of the prior doses of furosemide. CONCLUSIONS: Most patients with chronic CHF who were clinically stabilized on high doses of furosemide remained stable on a maintenance dose equal to one-third of the dose needed for their stabilization. Patients unable to tolerate the dose reduction regained their previous clinical status following the resumption of the prior diuretic doses.