Background: Docetaxel (DT) is an extensively used taxane, frequently associated with hypersensitivity reactions. The aim of this study was to record the epidemiological and clinical features of hypersensitivity to DT in non-small cell lung cancer patients in order to obtain useful information concerning the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. Methods: We retrospectively reviewed records of 620 non-small cell lung cancer patients treated with DT-containing regimens in the adjuvant, first-, second- or next-line setting. Data from 102 patients who had exhibited hypersensitivity reactions were analyzed according to the Common Toxicity Criteria for Adverse Events version 3.0. Five patients were chosen for the desensitization protocol. We applied the standard protocol for parenteral desensitization to β-lactam antibiotics, and DT treatment was carried out with a series of 10-fold dilutions in sufficient volume to administer the total dose. Results: One hundred and two patients (16.5%) were recorded as having hypersensitivity to DT. Reactions were observed after approximately 2.5 ± 1.0 cycles. Only 14 patients (14/620, 2%) developed grade 3–4 hypersensitivity. Reactions were more likely in patients during second- or third-line chemotherapy, but no other correlation (age, gender, atopic status) was observed. Five patients completed a parenteral desensitization protocol and continued their treatment uneventfully. Conclusions: Hypersensitivity reactions to DT respond quickly to discontinuation along with appropriate supportive care. Premedication and increased infusion time may allow readministration. The desensitization protocol that we developed provides a reliable alternative to permanent discontinuation of DT.

With 69 years being the median age at diagnosis in the United States, management of elderly patients with advanced non-small cell lung cancer (NSCLC) has become a common problem faced by the oncology practitioner. We evaluated a biweekly administration of the combination regimen using docetaxel (Sanofi Aventis, Athens) and gemcitabine (Eli Lilly, Athens) in a phase II study (objective response rate, median survival, median response duration and safety). A total of 198 cycles were administered to 38 patients with advanced NSCLC with a median age of 72 years (range 65-85 years). Patients received docetaxel 80 mg/m(2 )and gemcitabine 1000 mg/m (2 )on days 1 and 14 of a 28-day cycle. Twenty patients achieved a partial response (PR) (20/34, 58.8%), 4 patients had stable disease (SD) (4/34, 11.7%) and 10 (10/34, 29.4%) had progressive disease (PD). The median time to disease progression was 3 months (range 1-11 months) with a mean survival of 7 months (range 1-29 months). Hematological and non-hematological toxic effects were generally mild to moderate and manageable: grade 3 neurotoxicity and grade 3 allergy occurred in 5 patients (13.1%) and 1 patient (2.6%), respectively. Peripheral neuropathy, mostly grades 1 and 2, was reported in 29 patients (76.3%), which was seen more frequently in patients >70 years of age (P=0.048).We conclude that the biweekly administration of a docetaxel/gemcitabine combination with G-CSF support constitutes a tolerable and convenient regimen for the treatment of elderly patients with advanced NSCLC, with efficacy similar to that reported in other regimens. Hence, this two-drug combination appears promising and warrants further evaluation.

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Giant reactions to the tuberculin skin test are extremely rare and have been previously reported almost exclusively in patients with lepromatous leprosy. We herein report a giant tuberculin reaction associated with the homeopathic drug Tuberculinum in a patient with no evidence of active tuberculosis or leprosy.

BackgroundChest radiation is a common therapeutic approach in the management of lung cancer, as well as in other malignancies, rendering radiation-induced pneumonitis a rather commonly reported adverse event. A large proportion of patients undergoing radiation have underlying chronic obstructive pulmonary disease (COPD). We aim to elucidate the pathogenetic pathways implicated in radiation-induced pneumonitis particularly in this subgroup of patients.MethodsA literature search was performed in PubMed to identify relative studies published until June 2011.ResultsThe incidence of radiation-induced pneumonitis after conventional irradiation in COPD is about 7 to 10% in the moderate although symptomatic forms and about 1 to 3% in the severe forms. Radiation-induced pneumonitis seems to be an acute-phase reaction, taking primarily place in the most radiosensitive subunit of the lung, the alveolar/capillary complex. Reactive oxygen species, generated by radiation, initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating inflammation and chronic oxidative stress. COPD is characterized by a chronic inflammatory state in the lung, also generating reactive oxidant species. Biological markers intrinsic to the patient, such as early variations of certain cytokines (IL-6, IL-10, TGF-β) seem to be implicated and studies are under way to determine their role. The standard dose-volume metrics, such as V20, V13 and mean lung dose, are major factors influencing the clinical course of radiation-induced pneumonitis.ConclusionsUnderstanding the underlying pathogenesis of radiation-induced pneumonitis may help improve optimal delivery of treatment plans, minimize the risks and increasing the therapeutic ratio in patients with COPD.

BackgroundPulmonary toxicity and respiratory failure are major adverse events complicating the use of novel antineoplastic agents in the treatment of lung cancer. We aim to investigate the risk and characteristics of cytostatic-induced pulmonary toxicity caused by agents currently used to treat lung cancer.MethodsA literature search was performed in PubMed to identify relative studies published until June 2011.ResultsAlmost all categories of antineoplastic agents have been associated with some kind of pulmonary complications. Taxanes have been linked to acute pneumonitis, pleural effusion and reactions during infusion. Nucleoside analogs can cause diffuse alveolar damage, bronchospasm and acute respiratory distress syndrome (ARDS). Monoclonal antibodies are associated with pulmonary hemorrhage and hemoptysis. Acute pneumonitis and hypersensitivity reactions have been reported with podophyllotoxins, while diffuse interstitial pneumonia has been attributed to pemetrexed. Tyrosine kinase inhibitors of the epidermal growth factor receptor have been associated with acute pneumonitis, diffuse alveolar damage and pulmonary fibrosis. The exact incidence of lung toxicity caused by these agents remains unclear, although it seems relatively low. Clinical manifestation includes cough, fever, dyspnea and hypoxemia. Chest imaging reveals diffuse or patchy, unilateral or bilateral, ground-glass opacities or consolidations. It is important that other possible causes of respiratory failure be excluded when treating a lung cancer patient receiving chemotherapy.ConclusionsPhysicians should be aware of the potential of lung toxicities from antineoplastic agents, especially when they are combined with other cytotoxic drugs or radiation.

BackgroundLung cancer remains the leading cause of cancer-related deaths among men and women in the civilized world. A notable number of patients undergo radiation in various stages of the treatment process and its main respiratory side effect is pneumonitis. Our aim was to investigate the diagnostic and treatment methods of post-radiation pneumonitis particularly in asthma patients.MethodsA literature search was performed in Pubmed to identify relative studies published until June 2011. Lung cancer, post-radiation pneumonitis, therapy and asthma were the key words used for the search.ResultsPost-radiation pneumonitis is a clinical situation demanding early diagnosis in asthma patients, but the latter is often underestimated. Pneumonitis is clinically revealed by dyspnea, cough, fever and usually begins up to 12 weeks after the start of radiation treatment. Radiographically, it appears as diffuse or patchy consolidation and/or ground glass opacities. Pulmonary function decline is correlated to decreased values of forced expiratory volume in the 1st second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO). The effects on normal tissue may mimic or hide tumor recurrence. Smoking cessation causes changes of total lung capacity and vital capacity and this may have consequences on lung volume results in dose volume histogram analysis, targeting precision, oxygenation changes, tumor biology (gene expression) and prognosis. NCI Common Toxicity Criteria (CTC) V3.0 assessments are usually preformed weekly during radiotherapy and at regular follow-up visits. Complication rates vary with dose, fractionation, schedule duration, technique, photons' energy, irradiated volume, dose escalation, accelerated fractionation schemes, fields, co-morbidities and concurrent chemo-radiotherapy.ConclusionsThe crucially deteriorating on therapy effect of pneumonitis leads to the realization that alertness and constant attention is not only strongly advised, but compulsory in asthma patients.

BackgroundThe relationship between inflammation, air obstruction and lung cancer is complex and there is still great uncertainty regarding their underlying pathophysiology. Our aim was to investigate the inflammation pathways that are implicated in both chronic obstructive pulmonary disease (COPD) and lung cancer.MethodsA literature search was performed in PubMed to identify relative studies published until June 2011.ResultsThe pathophysiology of both COPD and lung cancer includes dysregulation of the inflammation process, but the cascade of signaling events is not yet fully understood. Both lung cancer and COPD are associated with cigarette smoking that induces a chronic inflammatory state in the lung by generating reactive oxidant species. It is considered that shared inflammatory pathways involve genetic and epigenetic changes due to chronic tissue injury and abnormal tumor immunity in susceptible hosts. The proposed role of chronic inflammation is based on the 2-stage model of carcinogenesis. According to this model, genotoxic injury is crucial in tumorigenesis, followed by promotional events that result in clonal growth of modulated cells. Research has shown that chronic inflammation creates the necessary environment for the development of lung cancer, acting as a tumor promoter. This environment, in combination with cigarette smoke, induces the upregulation of mediators of the inflammatory response, such as cyclooxygenase-2. This leads to the production of inflammatory cytokines through lymphocytes, such as IL-1, IL-6, IL-8 and IL-10, as well as to the increased formation of chemotactic factors. Some of the latter mediators may suppress cell mediated immune response and promote angiogenesis. They also impact cell growth, resulting in the inhibition of apoptosis. Inflammatory factors promote oxidative stress, contribute to the generation of reactive oxygen, and cause oxidative DNA base modification. COX-2 also plays an important role in promoting epithelial-to-mesenchymal transition, present in both lung cancer and COPD. Thus, chronic inflammation plays a pathogenic role in lung cancer by inducing preneoplastic mutations and cellular damage.ConclusionsAdditional research is required to understand the cellular and molecular mechanisms that link COPD and lung cancer, in an effort to discover new methods of prevention and treatment.