Survival outcomes in patients with advanced non-small cell lung cancer treated with erlotinib: expanded access programme data from Belgium (the TRUST study).

Erlotinib has been shown to prolong progression-free (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). We report here on effectiveness data on the subsample of 261 patients from 40 centres in Belgium involved in the TRUST study. Median age was 63 years. Most (69.0%) were male and current/former smokers (84.7%); with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (74.3%), stage IV disease (75.1%) and adenocarcinoma by histology (54.0%). Erlotinib was administered mainly as second- (47.1%) or third-line treatment (48.3%). Response rate was 6.5%; disease control rate 58.3%. Median PFS was 2.2 months. Better PS (P = 0.0384), stage IIIB disease (P = 0.0018) and presence of rash (P < 0.0001) were associated with longer PFS. OS rates at 1, 2 and 3 years were 26.4%, 10.9% and 6.4% respectively. Median OS was 5.9 months. Female gender (P = 0.007), better PS (P < 0.0001), stage IIIB disease (P = 0.0355) and presence of rash (P < 0.0001) were associated with longer OS. The findings confirm the therapeutic benefit of erlotinib in a broad range of patients in a sample from a country with a historically high lung cancer morbidity and mortality burden. Several determinants of PFS and OS are identified.

Changing preferences for information and participation in the last phase of life: a longitudinal study among newly diagnosed advanced lung cancer patients.

PURPOSE: The objective is to explore changes over time in the information and participation preferences of newly diagnosed stage IIIb/IV non-small-cell lung cancer patients. METHODS: Patients were recruited by physicians in 13 hospitals and interviewed every 2 months until the fourth and every 4 months until the sixth interview. RESULTS: Sixty-seven patients were interviewed three times. Over a period of 4 months from diagnosis, half of patients changed their information preferences for palliative care and end-of-life decisions with a possible or certain life-shortening effect (ELDs, e.g., non-treatment decisions) in both directions, from not wanting to wanting the information, but also--and as much--from wanting to no longer wanting it. The latter were more likely to be in a better physical condition. Preferences for participation in medical decision making also changed: 50% to 78%, depending on the type of decision (general, treatment, transfer or ELD), changed their preference towards wanting more or less participation. Pain seemed to be a trigger for patients wanting more involvement, which contrasts with studies suggesting that patients who are more ill tend to give up more control. CONCLUSIONS: Doctors should regularly ask their advanced lung cancer patients how much information and participation they want because preferences do change in unexpected ways.

A phase II EORTC study of temozolomide in patients with malignant pleural mesothelioma.

The aim of this study was to investigate the anti-tumour activity of temozolomide in patients with malignant pleural mesothelioma. 27 chemotherapy-naïve patients with histologically-proven malignant mesothelioma were treated with temozolomide 200 mg/m2/day, given orally on days 1-5 of each 28-day cycle. Therapy continued up to 10 cycles unless disease progression or excessive toxicity mandated discontinuation. Toxicity, symptom improvement and pain intensity were regularly assessed. With a median relative dose intensity of 97%, toxicity was moderate with grade 3 or more nausea, vomiting, thrombocytopenia, leucocytopenia, neutropenia, febrile leucocytopenia, arthralgia, infection and fever with infection occurring in 13, 13, 10, 3, 7 and 3% of patients for the remaining events, respectively. Overall, 1 objective response was observed (response rate 4%, 95% Confidence Interval (CI): 0.1-19). Median survival was 8.2 months. Symptom assessment showed no improvement and an increase of pain was observed during the study. Thus, oral temozolomide is an inactive agent in malignant mesothelioma.

Unilateral segmental hyperhidrosis associated with pulmonary adenocarcinoma.

This is the report of a 38-year-old man with unilateral dermatomal hyperhidrosis documented by a starch-iodine technique; a subsequent diagnosis was made of a generalized pulmonary adenocarcinoma. The association of unilateral hyperhidrosis and a malignant tumor is reviewed.

Ultrastructurally normal and motile spermatozoa in a fertile man with Kartagener's syndrome.

The findings in a 40-year-old man with Kartagener's triad (sinusitis, bronchiectasis, and situs inversus) and corrected transposition of the great vessels are presented. Electron microscopy revealed normal ultrastructure of the axoneme in both respiratory cilia and sperm tails. Light microscopic evaluation of the spermatozoa showed 50 percent motility, suggesting normal fertility. This assumption is confirmed, as the patient has two children. We suggest that an abnormal, uncoordinated motility pattern of the ultrastructurally normal respiratory cilia results in improper mucociliary clearance. This coordination is not needed in swimming spermatozoa, which could explain the apparent paradox between bronchopulmonary symptoms and normal fertility in our patient.

Second primary lung cancer in Flanders: frequency, clinical presentation, treatment and prognosis.

Patient and tumour characteristics of 23 patients presenting with a second primary lung cancer were analysed and compared with 534 patients with radically resected stage 1 non-small cell lung cancer (NSCLC). None of these characteristics is associated with a higher occurrence rate for second primary lung cancer. Prognosis in the latter patients is significantly worse than after resection of a 'solitary' NSCLC: the median survival time (MST) after resection of the first tumour is 50 months; after diagnosis of the second tumour only 14 months. Surgically retreated patients have a prognosis that is similar to that after resection of a 'solitary' NSCLC. No separate independent prognostic factors responsible for this survival difference could be isolated. Squamous histology and central location are associated with a longer recurrence free survival time. We conclude that the occurrence of a second primary lung cancer can not be predicted based on patient or tumour characteristics and that only surgical retreatment offers a chance of long survival in these patients.

Spontaneous pneumothorax in lymphomatoid granulomatosis.

Lymphomatoid granulomatosis is a unique form of pulmonary angiitis and granulomatosis characterized histologically by a necrotizing angiocentric and angiodestructive lymphoid infiltrate, which in most cases represents a proliferation of Epstein-Barr virus infected B-cells, with a prominent T-cell reaction. The most common radiographic findings in lymphoma-toid granulomatosis are multiple rounded mass densities, often suggestive of metastatic tumour. We report a case of spontaneous pneumothorax with bronchopleural fistula in a patient suffering from lymphomatoid granulomatosis.

Use of an Amplatzer Device for Endoscopic Closure of a Large Bronchopleural Fistula following Lobectomy for a Stage I Squamous Cell Carcinoma.

Bronchopleural fistulas can occur as a rare but severe complication after pulmonary resection. Established guidelines for the proper treatment of patients with bronchopleural fistulas do not exist. Apart from attempts to close the fistula, emphasis is placed on preventive measures, early treatment with antibiotics, drainage of the empyema and aggressive nutritional and rehabilitative support. For inoperable patients, endoscopic procedures are the only therapeutic option. Unfortunately, large (>8 mm) or central bronchopleural fistulas are usually not suitable for such endoscopic management. Recently, some groups have published a few case reports about a novel technique for the endobronchial closure of bronchopleural fistulas, using an Amplatzer device, originally designed for transcatheter closure of cardiac septal defects. We applied the same technique as a life-saving treatment in a ventilated patient who was considered inoperable due to a high oxygen need. The operation was successful. The patient could be weaned from ventilation and was eventually discharged from the hospital to a rehabilitation facility several weeks after the insertion of the device. Until now, endoscopic techniques have only been useful for the treatment of small, peripheral, bronchopleural fistulas and even then only as a bridge to surgery in high-risk surgical patients. In this case report, we demonstrate that the use of an Amplatzer device can expand the importance of endoscopic techniques in the treatment of bronchopleural fistulas. An Amplatzer device, for endobronchial closure, can indeed be administered for large and central bronchopleural fistulas. Moreover, it can be considered as a definite alternative to surgery in inoperable patients.

Long-term disease control of a non-operable neuroendocrine tumor of the lung with lanreotide: a case study.

Bronchopulmonary neuroendocrine tumors (NETs) are malignant tumors that represent approximately 20% of all lung cancers. The therapeutic option for advanced or metastatic bronchopulmonary NETs is mainly palliation of symptoms; options need to be individualized and, therefore, rely on the knowledge of multidisciplinary teams. Somatostatin analogs have been widely used in NETs for control of hormonal syndromes and are currently under evaluation for their antiproliferative activity. Here, we present a case of NET of the lung, for which we achieved long-term disease control with a treatment comprising the somatostatin analog lanreotide Autogel(®) in a patient with limited therapeutic options due to considerable comorbidity, while preserving his quality of life.

Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu.

Human epidermal growth factor receptor (HER)2/neu kinase domain mutations are found in approximately 1-4% of lung adenocarcinomas with a similar phenotype to tumors with epidermal growth factor receptor (EGFR) mutations. Afatinib is a potent irreversible ErbB family blocker. We determined the tumor genomic status of the EGFR and HER2 genes in non- or light smokers with lung adenocarcinoma in patients who were entered into an exploratory Phase II study with afatinib. Five patients with a non-smoking history and metastatic lung adenocarcinomas bearing mutations in the kinase domain of HER2 gene were identified, three of which were evaluable for response. Objective response was observed in all three patients, even after failure of other EGFR- and/or HER2-targeted treatments; the case histories of these patients are described in this report. These findings suggest that afatinib is a potential novel treatment option for this subgroup of patients, even when other EGFR and HER2 targeting treatments have failed.

Observational Aranesp Survey to Investigate the Q3W Schedule (OASIS): a prospective observational study of treatment of chemotherapy-induced anaemia with every 3 weeks darbepoetin alfa.

INTRODUCTION: This prospective observational study examined the adherence to published European guidelines on erythropoiesis-stimulating agents (ESAs) and the pattern of use and effect of darbepoetin alfa (DA) 500 microg once every 3 weeks (Q3W) for the treatment of chemotherapy-induced anaemia (CIA). MATERIALS AND METHODS: A total of 293 patients were included (263 solid tumour, 30 haematologic malignancy). Their mean age was 63 years, 51% were male, 57% had platinum-based chemotherapy. DA was started at a haemoglobin (Hb) level between 9 and 11 g/dL in 82% of patients. RESULTS AND DISCUSSION: In an analysis correcting for transfusions, 55% of patients achieved > or =2 g/dL increase in Hb, and a Hb level of >11 g/dL was reached in 81%. Transfusion rate was 27%. Most patients (70%) were treated in a Q3W chemotherapy, and planned synchronisation of chemotherapy and Q3W DA could be maintained in 76%. CONCLUSION: Adherence to European guidelines for DA treatment was good, and Q3W DA treatment was in synchronisation with Q3W chemotherapy in the majority of the patients, thereby reproducing the findings of a recent phase III study.

Gefitinib monotherapy in advanced nonsmall cell lung cancer: a large Western community implementation study.

Epidermal growth factor receptor tyrosine kinase inhibitors represent a new treatment option for patients with advanced nonsmall cell lung cancer (NSCLC). This retrospective study examined to what extent previous clinical trial experience matches large-scale Western community implementation of this treatment. In the Belgian expanded access programme, the data from 513 patients with advanced or metastatic NSCLC, not suitable for further chemotherapy and receiving oral gefitinib 250 mg.day(-1) until disease progression, death or unacceptable toxicity, were analysed. The median (range) duration of gefitinib treatment was 2.3 months (0.0-32.7). Its use was predominantly in second- or third-line treatment. The overall response and disease control rates were 8.9 and 41.2%, respectively. In univariate analysis, response was more common in females and never-smokers. In multivariate analysis, female sex was the only significant predictive factor (odds ratio (OR) (95% confidence interval (CI)) 0.329 (0.129-0.839)). Symptom improvement was reported in 108 patients of whom 32 (29.6%) had an objective response, 66 (61.1%) experienced disease stabilisation and 10 (9.3%) progressed. Gefitinib was well tolerated; only 7.8% of the patients reported grade 3 or 4 toxicity. The overall median survival was 4.7 months, with a 1-yr survival rate of 21%. Survival was strongly influenced by a better performance status (PS) (good PS: hazard ratio (HR) (95%CI) 0.110 (0.077-0.157)) and adenocarcinoma with bronchioloalveolar carcinoma features histology (HR (95%CI) 0.483 (0.279-0.834)). In conclusion, the activity of gefitinib was confirmed in the present large Western community implementation study. Response, present in a small subgroup, led to a rewarding survival and could be predicted by sex only. Baseline performance status and adenocarcinoma with bronchioloalveolar carcinoma features histology were significant factors for survival.

Necrotizing sarcoid granulomatosis with uveitis: a variant of sarcoidosis?

A patient with malaise, uveitis and a nodular infiltrate in the left lower lobe of the lung is described. An open lung biopsy established the diagnosis of necrotizing sarcoid granulomatosis. The differential diagnosis of necrotizing sarcoid granulomatosis with sarcoidosis and angiocentric granulomatosis (Wegener's disease) is extensively discussed. Our case illustrates that NSG and sarcoidosis could be pathogenetically related.

Pulmonary fat embolism presenting as chronic respiratory failure.

A patient is presented with progressive respiratory failure, caused by pulmonary fat embolism as proved by an open lung biopsy. Four and a half yrs earlier, she underwent a right hip operation. We surmise that a loosening hip prosthesis caused the marrow embolisation.

Insertion of a self-expandable endotracheal metal stent using topical anaesthesia and a fibreoptic bronchoscope: a comfortable way to offer palliation.

A self-expandable stent was used to obtain prolonged relief of stridor resulting from tracheal obstruction by extrinsic tumour compression despite prior external irradiation. The stent was inserted in an easy and comfortable procedure with fibreoptic bronchoscopy under local anaesthesia.

Postendoscopic sphincterotomy stenosis.

We report on two patients. The first patient is a 62-year-old female patient who had cholecystectomy in 1970, and in whom two small bile duct stones were removed after endoscopic sphincterotomy in 1987. Within two months of this procedure, she developed three episodes of documented acute pancreatitis. The other patient, a 58-year-old female, developed acute pancreatitis three months after an endoscopic sphincterotomy for stones in the common bile duct. In both patients, ERCP revealed a cicatricial stenosis of the common bile duct and the pancreatic duct. The condition was resolved by repeat sphincterotomy. The first patient needed repeated endoscopic insertion of bilioduodenal endoprostheses and an endoprosthesis in the pancreatic duct. It is interesting to note that, in contrast to surgical reports, very few postpapillotomy stenoses are reported by endoscopists.