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Inhibition of specific processes essential for tumour vascular development is one of the key strategies for the treatment of non- small cell lung cancer (NSCLC). Many agents target the Vascular Endothelial Growth Factor (VEGF) pathway, either by preventing VEGF receptor binding or inhibiting VEGF receptor signalling in endothelial cells. Bevacizumab is a monoclonal antibody specific for VEGF-A. Combination of bevacizumab with standard first-line chemotherapy in NSCLC leads to an improvement in response rates and progression-free survival compared to chemotherapy alone and a significant survival advantage with carboplatin- paclitaxel chemotherapy. Toxicity issues are of concern with the possible occurrence of hypertension and an increased risk of arterial thrombo-embolism. The occurrence of fatal pulmonary haemorrhage after necrosis of the primary tumour is a specific toxicity in NSCLC which requires appropriate selection of patients before treatment; excluding squamous cell carcinoma, haemorrhagic tumours and tumour invasion of major blood vessels. The use of bevacizumab combined with chemotherapy represent a first step in the development of antiangiogenic treatments in NSCLC, with the future possibility of using it in earlier stages of disease.

The epidermal growth factor receptor (EGFR) plays an important role in non-small cell lung cancer growth. Small molecules can specifically target the tyrosine kinase activity of the EGFR's intracellular domain and thus inhibit downstream pathways influencing cell proliferation and survival. Gefitinib and erlotinib have been developed as single-agents for the treatment of patients who have relapsed following one or more courses of chemotherapy. Erlotinib has exhibited significant overall survival benefit in a second- or third-line setting compared to placebo for unselected patients. A beneficial effect on survival has been observed in almost all subgroups of patients and the response rate was higher in women, non-smokers, Asian patients and patients with adenocarcinoma. Somatic mutations in the tyrosine kinase domain of EGFR have been shown to be strong predictive markers for drug response to gefitinib or erlotinib and led to a new insight into adenocarcinoma carcinogenesis. High EGFR gene copy number seems to be predictive of EGFR tyrosine kinase inhibitors-related effect on survival observed in second- or third-line treatment. Future use of EFGR tyrosine kinase inhibitors should be based on improved clinical and molecular selection of patients who are likely to derive the greatest benefit from these drugs, especially in first-line setting.

The development of new anticancer agents specifically targeting the molecular processes involved in carcinogenesis is a major step forward in the treatment of patients with lung cancer. Preclinical models often show a cytostatic mechanism of action and predict an improved toxicity profile compared to traditional cytostatic drugs. This means that a standard development design based upon tumour shrinkage is not appropriate for these agents. The development of targeted therapies requires a new model for clinical phase I and II trials, with careful selection of patients who might benefit from treatment and adapted endpoints to establish that growth inhibition can be translated into a clinical benefit. Some targeted agents may have been discarded because of the use of inappropriate traditional endpoints during their development. A greater investment with additional implementation of correlative translational and pharmacodynamic studies during early development is crucial before going to phase III trials.

Treatment of stage IV non-small cell lung cancer (NSCLC) is based upon chemotherapy, with several meta-analyses showing an improvement of survival compared to supportive care alone. For first-line chemotherapy, the development of new third generation drugs (vinorelbine, gemcitabine, paclitaxel, docétaxel) with a better therapeutic index has led to the definition of 4 to 6 cycles of a platinum-based dual agent regime as standard therapy for performance stage (PS) 0-1 patients, producing a 1-year survival in the region of 35%. The choice of agents is based upon the differences in the toxicity profile of platinum-based combinations and on patient co-morbidities. For frail patients (PS>2 and elderly patients), single-agent chemotherapy seems more appropriate than cisplatin-based combinations; carboplatin or non-platinum combinations might be more effective. Third generation cytotoxic agents have modestly improved survival for patients with stage IV NSCLC but should probably provide an increased number of long-term survivors.

Purpose: Determine the response to, and toxicity of docetaxel (Taxotere) in patients (pts) with inoperable non-small-cell lung cancer (NSCLC) previously treated with platinum-containing chemotherapy., Patients and Methods: Twenty-seven patients with stage IIIB or IV NSCLC, having received one platinum-containing regimen were treated with 100 mg/m2/3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with prednisolone and diosmin was given in all patients. Antitumoral activity was assessable in 21/27 pts. Median age: 52 years; WHO performance status 0-1: 77% pts, stage IV disease: 63% pts., Results: 6/21 eligible pts (24%) achieved a partial response to treatment [C.I 95%: 5.6-42]. Median time to progression: 2.9 months, median survival: 8.5 months with a median follow-up of 23.7 months (range: 13.5-27). Hematologic toxicity: grade 3-4 neutropenia: 75% pts, febrile neutropenia: 11% cycles. Non hematologic toxicities: fluid retention, rash, alopecia, sensory neuropathy, asthenia, and nail changes., Conclusion: Docetaxel (Taxotere) administered at 100 mg/m2/3 weeks has relevant clinical activity against platinum treated NSCLC pts. Neutropenia is the main toxicity.

We report a case of interstitial pneumonia found by a woman who suffered from a gastroesophageal reflux unamenable to usual treatments. The HR-tomographic discovery of a tone esophagus lead to a manometric study. The association of high autoantibodies levels and radiographic and manometric data were characteristic of esophageal and pulmonary scleroderma.

Docetaxel, a new chemotherapeutic agent, has demonstrated activity in non-small cell lung cancer and breast cancer. Toxicities associated with treatment using docetaxel include hypersensitivity reactions and fluid retention, which can be prevented by pretreatment with corticosteroids. We describe herein two cases of acute interstitial pneumonitis after administration of docetaxel to patients suffering from metastatic non-small cell lung cancer. A pulmonary toxicity of docetaxel from an hypersensitivity reaction is likely because of symptoms course, radiological demonstration of an interstitial pneumonitis, lack of an infectious etiology and of clinical response to antibiotic treatment, and rapid recovery with corticosteroids. This unusual pulmonary toxicity has been rarely described with docetaxel, as transient pulmonary infiltrates have been observed during treatment with paclitaxel. The possibility of an hypersensitivity pneumonitis must be taken into account when a patient with docetaxel treatment presents pulmonary infiltrates.

A 52-year-old man presented with a two month history of left sided chest pains related to a pleurisy which showed an 18 per cent eosinophilia on pleural aspiration. He was hospitalised one month later and at that stage was very dyspnoeic and there was a bilateral pleural effusion associated with a significant pericardial effusion causing compression. A pleuro-pericardial drainage eased the patient's symptoms. The pleural fluid showed an 87 per cent lymphocytosis and a complete diagnostic work up was negative thus a diagnosis of idiopathic eosinophilic pleurisy with an associated pericarditis was made. Steroid therapy was instituted using half a milligram per kilo and this led to a rapid functional improvement and no recurrence of the effusions were noted. The treatment was progressively stepped down over the next five months and the patient's condition was satisfactory without any recurrence at nine months.

Pleurisies due to the syndrome of ovarian hyperstimulation typically accompany ascites and in their most severe form are associated with haemoconcentration, hypovolaemia and thromboembolic phenomena. It is not unusual in this context for pleural effusions to be isolated. They may occur during treatment for sterility by inducing ovulation, they are exudates and predominantly right sided. The pathophysiology is not clear and results in vascular hyperpermeability. Currently, no treatment aimed at the aetiology has proven its own efficacy. Spontaneous regression of the effusion is the rule but in severe forms, where the prognosis is uncertain, correction of hypovolaemia is a priority.

Mastocytosis (MS) may be exclusively cutaneous or, more rarely, systemic. MS may be indolent (benign), aggressive, leukaemic or associated with a myeloproliferative disorder. The clinical expression of MS may be secondary to the direct consequences of the development of mastocytes in tissue or correspond to the paroxysmal features related to the liberation of vasoactive and spasmogenic mediators by activated mastocytes. Dyspnoeic episodes are classical but the physiopathological mechanism is poorly documented. True asthma or bronchopulmonary mastocytosis seems rare. The authors report evidence of non-specific bronchial hyper-reactivity (HRB) to Carbachol in a patient effected with benign cutaneous mastocytosis with secondary elevation of the total serum IGE. Factors determining the HIB are discussed and appear primarily linked to the mastocytosis.

The authors report the case of a patient aged 27 suffering from a clear cell adenocarcinoma of the vagina which was related to her mother taking Diethylstilboestrol or Distilbene (DES) during her pregnancy. This young woman presented with pulmonary metastases for which several trials of chemotherapy ended in failure. The case raises several problems amongst which are epidemiologies of cancers induced by Diethylstilboestrol (DES), their prognosis as well as the therapeutic strategies at the time of diagnosis and the recurrences which occur as metastases.