Real world data of efficacy and safety of erlotinib as first-line TKI treatment in EGFR mutation-positive advanced non-small cell lung cancer: Results from the EGFR-2013-CPHG study.

BACKGROUND: Phase III clinical trials have demonstrated the merits of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) in the treatment of non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. Using a cohort of unselected patients treated with erlotinib, we sought to further describe patient and tumour characteristics, and to evaluate their progression-free survival (PFS) and overall survival (OS). METHODS: Overall, 44 pulmonologists included patients with the required characteristics as follows: Stage IIIB-IV NSCLC, EGFR-activating mutation, age≥18 years, and having to start erlotinib therapy or receiving erlotinib therapy as the first-line TKI, regardless of treatment-line. The analyses were performed using R software, with survival rates calculated according to the Kaplan-Meier method. RESULTS: A total of 177 patients, aged 72 years on average, were enrolled over a 2-year period. The cohort included 123 women (69.5%), 158 Caucasians (89.3%), 112 non-smokers (63.2%), and 167 adenocarcinomas (94.3%), at either stage IIIB (21) or IV (156), with a good performance status (PS 0-1, 127). Overall, 40 exhibited brain metastases at baseline (22.6%), while 75 had undergone earlier treatment (42.4%). Median PFS was 11.7 months and OS 25.8 months, with respectively a 1-year rate of 48.6% and 74%. The risk of death correlated with ECOG status (PS=2, HR=4.48, P<0.001) but not with brain metastasis (HR=1.67, P=0.278). CONCLUSIONS: This study has confirmed erlotinib's efficacy and safety for unselected patients, with PFS and OS comparable to those obtained in phase III trials.

Baclofen therapy for chronic hiccup.

Chronic hiccup is a rare but potentially severe condition, that can be symptomatic of a variety of diseases, or idiopathic. Many therapeutic interventions have been reported, most often as case reports. Among other drugs, baclofen has been suggested as a therapy for chronic hiccup. In a large series of patients, we have evaluated its therapeutic position. In patients with chronic hiccup, defined as hiccup spell or recurring hiccup attacks lasting more than 7 days, investigation of the upper gastro-oesophageal tract (fibroscopy, manometry, and pH monitoring) was systematically performed. Most patients had tried numerous drugs in the past, without success. Baclofen was used as a first treatment in patients without evidence of any gastro-oesophageal disease (n = 17), and was undertaken only after full treatment of such disease (n = 55) had failed to solve the hiccup problem (n = 20). Baclofen has, therefore, been administered to 37 patients with chronic hiccup (average duration 4.6 yrs). Baclofen produced a long-term complete resolution (18 cases) or a considerable decrease (10 cases) of hiccups in 28 of the 37 patients. There was no significant difference between patients with or without gastro-oesophageal disease. We conclude that so-called idiopathic chronic hiccup often results from gastro-oesophageal abnormalities. Also, if controlled studies confirm our encouraging results, baclofen can be a major element in the treatment of chronic hiccup that is idiopathic, or that cannot be helped by treatment of gastro-oesophageal diseases.

[Hiccups in adults]. / Le hoquet de l'adulte.

Hiccoughs are an involuntary spasmodic and coordinated contractions of the inspiratory muscles associated with a delayed and sudden closure of the glottis which is responsible for the characteristic noise. The pathophysiology of hiccoughs have not been elucidated. There have only been a few observations describing the sequence of inspiratory muscle activation and these suggest that the control of hiccoughs is within the central nervous system. The clinical circumstances associated with acute benign hiccoughs are both numerous and disparate. In these cases, when they stop spontaneously or as a result of simple physical manoeuvres hiccoughs do not require any particular medical attention. Chronic hiccoughs, defined as hiccoughs persisting for more than 24 hours or recurring as repetitive attacks are a rare phenomenon. The causes cover the whole of organic pathology. Systematic protocols of complementary examinations most often enable an underlying organic cause to be found. Amongst these, particular attention should be paid to oesophageal causes by the reason of their being the most frequent. An important place should be reserved for the aetiological treatment as is frequently enables a remission of chronic hiccough.

Hiccup in adults: an overview.

Hiccup is a forceful, involuntary inspiration commonly experienced by fetuses, children and adults. Its purpose is unknown and its pathophysiology still poorly understood. Short hiccup bouts are mostly associated with gastric distention or alcohol intake, resolve spontaneously or with simple folk remedies and do not require medical attention. In contrast, prolonged hiccup is a rare but disabling condition which can induce depression, weight loss and sleep deprivation. A wide variety of pathological conditions can cause chronic hiccup: myocardial infarction, brain tumour, renal failure, prostate cancer, abdominal surgery etc. Detailed medical history and physical examinations will often guide diagnostic investigations (abdominal ultrasound, chest or brain CT scan...). Gastric and duodenal ulcers, gastritis, oesophageal reflux and oesophagitis are commonly observed in chronic hiccup patients and upper gastrointestinal investigations (endoscopy, pH monitoring and manometry) should be included in the diagnostic evaluation systematically. Etiological treatment is not always available and chronic hiccup treatment has classically relied on metoclopramide and chlorpromazine. Recently, baclofen (LIORESAL) has emerged as a safe and often effective treatment.

[Chronic hiccups]. / Le hoquet chronique.

We report 18 cases of chronic hiccup (defined as lasting for more than 48 hours) in adults. Among the numerous possible causes, reflux esophagitis proved to be by far the most frequent (50% of the cases). However, hiccup often initiated a self-perpetuating vicious circle. This is possibly because hiccup per se can give esophageal dyskinesia, which in turn leads to gastro-esophageal reflux. The treatment was difficult and whenever possible has been directed chiefly towards the cause. However hiccup remained intractable in many cases even after a possible cause had been adequately cured (e.g., successful Nissen procedure in reflux cases). Central nervous system depressants and myorelaxing drugs were not very helpful, except for baclofen (initial response rate = 60%).

Diagnosis of pulmonary embolism by transoesophageal echocardiography.

A 68-year-old woman was admitted for major dyspnoea. A transoesophageal echocardiogram was performed after the occurrence of acute circulatory shock. During the examination, the patient was under mechanical ventilation. We found a thrombus that had almost occluded the right pulmonary artery and which was later confirmed by selective angiography. Despite treatment, the patient died 2 days later; autopsy confirmed the thrombus in the right pulmonary artery.

[Treatment of reflex vagal hypertonia in infants. Role of diphemanil (apropos of 50 cases)]. / Traitement de l'hypertonie vagale réflexe du nourrisson. Place du diphémanil (à propos de 50 cas).

For a period of 20 months, 50 consecutive infants (mean age: 11 months) were given Diphemanil (atropine like synthetic drug) for reflex symptomatic bradycardia of probable vagal origin. Treatment's results were evaluated with the study of oculo-cardiac reflex (OCR) and Holter monitoring performed before and 3 months after the beginning of Diphemanil. If tolerance was generally good, it was not possible to demonstrate the clinical efficacy of the treatment on the whole group. However, assertive success was seen on individual cases. Holter and OCR data improved statistically. The other therapeutical means aiming at warning possible complications of the hypertonic vagal reflex were reviewed: inserting a cardiac pace-maker does not always prevent sudden death; a nodal sinus surgical selective denervation might be justified in certain exceptional cases, because of the severity of the spontaneous evolution or of the resistance to medical treatment.