Soon Hin How

First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study

BACKGROUND The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety. RESULTS A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP. CONCLUSION These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).

Learning curve for double-balloon enteroscopy: Findings from an analysis of 282 procedures

AIM To determine the learning curves for antegrade double-balloon enteroscopy (aDBE) and retrograde DBE (rDBE) by analyzing the technical success rates. METHODS A retrospective analysis in a tertiary referral center. This study reviewed all cases from June 2006 to April 2011 with a target lesion in the small-bowel identified by either capsule endoscopy or computed tomography scan posted for DBE examinations. Main outcome measurements were: (1) Technical success of aDBE defined by finding or excluding a target lesion after achieving sufficient length of small bowel intubation; and (2) Technical success for rDBE was defined by either finding the target lesion or achieving stable overtube placement in the ileum. RESULTS Two hundred and eighty two procedures fulfilled the inclusion criteria and were analyzed. These procedures were analyzed by blocks of 30 cases. There was no distinct learning curve for aDBE. Technical success rates for rDBE continued to rise over time, although on logistic regression analysis testing for trend, there was no significance (P = 0.09). The odds of success increased by a factor of 1.73 (95% CI: 0.93-3.22) for rDBE. For these data, it was estimated that at least 30-35 cases of rDBE under supervision were needed to achieve a good technical success of more than 75%. CONCLUSION There was no learning curve for aDBE. Technical success continued to increase over time for rDBE, although a learning curve could not be proven statistically. Approximately 30-35 cases of rDBE will be required for stable overtube intubation in ileum.

Bone mineral density in asthmatic patients on inhaled corticosteroids in a developing country.

INTRODUCTION: Prolonged use of oral corticosteroids is a risk factor for osteoporosis. However, the effect of inhaled corticosteroids (ICS) on bone mineral density (BMD) of asthmatic patients remains controversial. OBJECTIVES: We aimed to determine the prevalence of osteopenia and osteoporosis in our patients with asthma receiving ICSs for more than one year compared with patients who did not have asthma and to determine the risk factors for osteopenia and osteoporosis among the asthmatic patients. METHODS: This was a cross-sectional study conducted from August 2007 to July 2009. Asthmatic patients aged 18 years and older who had been on ICS for at least one year and a control group of subjects not on ICS were included. BMD was measured using DEXA (dual energy X-ray absorptiometry) scan. The WHO classification of T-scores for osteopenia and osteoporosis were used. RESULTS: A total of 143 subjects were recruited (69 asthmatics and 74 control subjects). T-scores of the spine, femur, and hip of the asthmatics vs the control subjects were mean, −0.72 vs −0.57 (P=0.98); median, −0.60 vs −0.80 (P=0.474); and mean, 0.19 vs 0.06 (P=0.275); respectively. T-scores of the spine, femur, and hip showed significant negative correlation with age and significant positive correlation with body mass index (BMI). CONCLUSION: The risk factors for osteoporosis and osteopenia among asthmatic patients were older age and lower BMI, but not the cumulative dose of ICS. Asthmatic patients on ICS have no added risk of osteoporosis or osteopenia as compared with non-asthmatic subjects.

Epidermal growth factor receptor mutations in non- small cell lung cancers in a multiethnic malaysian patient population.

BACKGROUND Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in non- small cell lung cancer (NSCLC) are predictive of response to EGFR-targeted therapy in advanced stages of disease. This study aimed to determine the frequency of EGFR mutations in NSCLCs and to correlate their presence with clinical characteristics in multiethnic Malaysian patients. MATERIALS AND METHODS In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction. RESULTS EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p<0.001] and in never smokers (62.5%) than in ever smokers (12.7%) (OR, 11.50; 95%CI, 5.08-26.03; p<0.001). Mutations were more common in adenocarcinoma (39.4%) compared to non-adenocarcinoma NSCLCs (15.8%) (p=0.072). The mutation rates in patients of different ethnicities were not significantly different (p=0.08). Never smoking status was the only clinical feature that independently predicted the presence of EGFR mutations (adjusted OR, 5.94; 95%CI, 1.94- 18.17; p=0.002). CONCLUSIONS In Malaysian patients with NSCLC, the EGFR mutation rate was similar to that in other Asian populations. EGFR mutations were significantly more common in female patients and in never smokers. Never smoking status was the only independent predictor for the presence of EGFR mutations.

Survival of lung cancer patients in a resource-limited country

Data on lung cancer survival are lacking in developing countries. Our objectives were to describe the survival of our lung cancer patients and to determine independent prognostic factors affecting survival.

Defaulters among lung cancer patients in a suburban district in a developing country.

INTRODUCTION: This study was carried out to determine the prevalence, patients characteristic and reasons for defaulting follow-up and treatment among patients with lung cancer. METHODS: Patients with histologically confirmed lung cancer were recruited. Patients detailed demographic data, occupation, socioeconomic status, and educational level of both the patients and their children were recorded. Defaulters were classified as either intermittent or persistent defaulters. By using Chi-square test, defaulter status was compared with various demographic and disease characteristic factors. The reasons for default were determined. RESULTS: Ninety five patients were recruited. Among them, 81.1% patients were males; 66.3% were Malays. The mean age (SD) was 60 ± 10.5 years. About 46.3% of the patients had Eastern Cooperation Oncology Group (ECOG) functional status 0/1 and 96.8% of the patients presented with advanced stage (Stage 3b or 4). Overall, 20 patients (21.1%) were defaulters (35.0% intermittent defaulters; 65.0% persistent defaulters). Among the intermittent defaulters, 8 patients defaulted once and one patient defaulted 3 times. Among the 20 defaulters, only 2 (10%) patients turned up for the second follow-up appointment after telephone reminder. Two main reasons for default were ‘too ill to come’ (38.5.5%) and logistic difficulties (23.1%). No correlation was found between patient education, children education, income, ECOG status, stage of the disease, race, and gender with the defaulter rate. CONCLUSION: Defaulter rate among lung cancer patients was 21.1%. Children education level is the only significant factor associated with the defaulter rate.

Intrapleural streptokinase for the treatment of chylothorax.

Chylothorax is suspected when milky white turbid fluid is obtained from thoracocentesis. Conservative management usually involves intercostal tube drainage, dietary restriction, and total parenteral nutrition. Surgery is indicated when conservative management fails. We describe a young woman with idiopathic chylothorax who failed conservative therapy but refused surgery. We instilled intrapleural streptokinase, which improved her condition.

Empyema Thoracis Complicated by Pneumothorax Necessitans Manifesting as Lobulated, Localized Subcutaneous Emphysematous Swellings

We describe a patient with empyema thoracis that had eroded through the apical chest wall to the supraclavicular fossa and lung parenchyma, ultimately leading to a bronchopleural fistula manifesting as lobulated, localized subcutaneous emphysematous swellings over the chest wall and supraclavicular fossa. This is a rarely reported phenomenon and the reason why the lobulated subcutaneous emphysematous swellings remained localized is unknown.