Adenocarcinoma ; drug therapy ; Antibodies, Monoclonal ; adverse effects ; Drug Resistance, Neoplasm ; Female ; Fever ; chemically induced ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; drug therapy ; Middle Aged ; Quinazolines ; therapeutic use

Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; Female ; Glutamates ; administration & dosage ; Guanine ; administration & dosage ; analogs & derivatives ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Neoplasm Metastasis ; Pemetrexed ; Quinazolines ; administration & dosage ; Stevens-Johnson Syndrome ; etiology

Gefitinib is regarded as a relatively safe agent for the treatment of an advanced non-small cell lung cancer (NSCLC). Pulmonary toxicity such as interstitial lung disease associated with gefitinib is uncommon with an estimated all time incidence around 1% worldwide. Moreover, a case of gefitinib associated with pulmonary cystic changes has not been reported yet. In this report we present a case of progressive multiple air cystic changes in both lungs in a patient with NSCLC and intrapulmonary metastases who underwent a gefitinib therapy.
Antineoplastic Agents/*adverse effects ; Brain Neoplasms/secondary ; Carcinoma, Non-Small-Cell Lung/*drug therapy/secondary ; Cysts/*chemically induced ; Female ; Humans ; Lung/pathology ; Lung Diseases/*chemically induced ; Lung Diseases, Interstitial ; Lung Neoplasms/*drug therapy ; Middle Aged ; Quinazolines/*adverse effects

BACKGROUNDThe preclinical experiments and several clinical studies showed icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in Chinese patients with advanced non-small cell lung cancer (NSCLC) who failed previous chemotherapy. We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients.

METHODSThe clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1, 2011 to July 31, 2012 were retrospectively analyzed. All patients were given icotinib treatment after the failure of previous chemotherapy. Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model.

RESULTSThe objective response rate was 33/149 and disease control rate was 105/149. No complete response occurred. Median progression free survival (PFS) with icotinib treatment was 5.03 months (95% CI: 3.51 to 6.55). Median overall survival was 12.3 months (95% CI: 10.68 to 13.92). Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS. At least one drug related adverse event was observed in 65.8% (98/149) of patients, but mostly grade 1 or 2 and reversible and none grade 4 toxicity.

CONCLUSIONSIcotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy. It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Crown Ethers ; adverse effects ; therapeutic use ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Quinazolines ; adverse effects ; therapeutic use ; Retrospective Studies

OBJECTIVETo investigate the protective effects of rutaecarpine (Rut) on right ventricular remodeling in rats with monocrotaline-induced pulmonary hypertension (PH).

METHODForty-eight SD rats were fed adaptively for 1 week and then were randomly divided into the following 4 groups (n = 12): normal control group, monocrotaline (MCT) treatment group, MCT treatment with Rut (20 mg/kg)group and MCT treatment with Rut (40 mg/kg) group. PH rats were induced by a single injection of monocrotaline (60 mg/kg, sc) and were administered with Rut (20 or 40 mg/kg/d) for 4 weeks. At the end of experiment, the right ventricular systolic pressure (RVSP) and mean pulmonary artery pressure (mPAP) were monitored via the right jugular vein catheterization into the right ventricle. The ratio of right ventricle (RV) to left ventricle (LV) + septum (S) and the ratio of RV to tibial length were calculated. Right ventricular morphological changes were deserved by HE staining. Masson's trichrome staining was used to display collagen deposition. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) levels in right ventricle were determined according to the manufacturer's instructions. mRNA and protein expression levels of NOX4, collagen I and collagen III were analyzed by immunohistochemisty, real-time PCR and Western blot.

RESULTSThe results showed that Rut treatment for 4 weeks attenuated RVSP, mPAP and right ventricular remodeling index (RV/LV + S and RV/Tibial length) of PH rats induced by monocrotaline. Furthermore, the right ventricular collagen deposition and collagen I and collagen I expression induced by MCT were both significantly suppressed by Rut. The expression levels of NOX4 and MDA were obviously decreased, while the T-AOC was significantly increased in right ventricular from PH rats treated with Rut.

CONCLUSIONThese results suggested that Rut ameliorates the right ventricular remodeling in rats with PH induced by MCT through down-regulating of NOX4 expression and collagen accumulation.

Animals ; Antioxidants ; metabolism ; Heart Ventricles ; metabolism ; Hypertension, Pulmonary ; chemically induced ; drug therapy ; Indole Alkaloids ; pharmacology ; Male ; Malondialdehyde ; metabolism ; Monocrotaline ; adverse effects ; NADPH Oxidase 4 ; NADPH Oxidases ; metabolism ; Quinazolines ; pharmacology ; Rats ; Ventricular Remodeling ; drug effects

Eperisone and afloqualone act by relaxing both skeletal and vascular smooth muscles to improve circulation and suppress pain reflex. These drugs are typically prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) as painkillers. However, there have been no reports on serious adverse reactions to oral muscle relaxants; and this is the first report to describe three allergic reactions caused by eperisone and afloqualone. All three patients had histories of allergic reactions after oral intake of multiple painkillers, including oral muscle relaxants and NSAIDs, for chronic muscle pain. An open-label oral challenge test was performed with each drug to confirm which drugs caused the systemic reactions. All patients experienced the same reactions within one hour after oral intake of eperisone or afloqualone. The severity of these reactions ranged from laryngeal edema to hypotension. To confirm that the systemic reaction was caused by eperisone or afloqualone, skin prick testing and intradermal skin tests were performed with eperisone or afloqualone extract in vivo, and basophil activity tests were performed after stimulation with these drugs in vitro. In one patient with laryngeal edema, the intradermal test with afloqualone extract had a positive result, and CD63 expression levels on basophils increased in a dose-dependent manner by stimulation with afloqualone. We report three allergic reactions caused by oral muscle relaxants that might be mediated by non-immunoglobulin E-mediated responses. Since oral muscle relaxants such as eperisone and afloqualone are commonly prescribed for chronic muscle pain and can induce severe allergic reactions, we should prescribe them carefully.
Female ; Humans ; Hypersensitivity/*etiology ; Middle Aged ; Muscle Relaxants, Central/*adverse effects ; Propiophenones/adverse effects ; Quinazolines/adverse effects

OBJECTIVETo establish the quality standards of the herbs of Peganum harmala.

METHODAccording to the Chinese Pharmacopoeia (2010 version, volume 1) and its appendix method, the water, total ash, acid insoluble ash, water-soluble extractives, and heavy metal were analyzed for herbs of P. harmala. TLC method was used to separate harmaline, harmine and vasicine from the herb samples by mixture of ethyl acetate-methanol-ammonia (10: 1.5: 0.5) as a developing solvent on high performance silica gel precoated plate (HSGF254) and to identify them inspected under UV 366 nm, visualized by spraying with both Dragendorff reagent, and by bioautographic assay. In the HPLC method, vasicine was separated on a C18 (4.6 mm x 250 mm, 5 microm) column with metnanol-0.1% trifluoroacetic acid (15:85) as the mobile phase and detected at at 280 nm.

RESULTIn the TLC procedures, 254 nm fluorescent and bioautographic assay for the detection of acetylcholinesterase inhibitor can be used for the qualitative identification of the active ingredients. For the HPLC quantitation method, the calibration curve of vasicine displayed ideal linearity over the range of 0.7923-792.3 mg x L(-1) with the regression equation of Y = 18,227X - 24.879 (r = 0.9999). The average recovery of vasicine was 101.6% with a RSD of 1.9%. The RSD values of intra-day and inter-day precision were less than 2%. The content of vasicine in 10 batches of herbs of P. harmala fluctuates between 0.23% and 1.47%.

CONCLUSIONThe results indicated that the limit of vasicine was not lower than 0.6%, and the water, total ash, acid insoluble ash, and water-soluble extractives were not more than 10.0%, 20.0%, 1.7%, and 30.0%, respectively. The heavy metal of plumbum, cadmium, arsenic, mercury, and copper were not more than 5, 3, 2, 2, and 20 mg x kg(-1), respectively. The qualitative and quantitative method established was suitable for the quality evaluation and assessment of herbs of P. harmala.

Alkaloids ; chemistry ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; standards ; Humans ; Metals, Heavy ; chemistry ; Peganum ; chemistry ; Quality Control ; Quinazolines ; chemistry

OBJECTIVETo observe the curative and adverse side effects of erlotinib in elderly patients with advanced non-small cell lung cancer (NSCLC).

METHODSSeven-two elderly patients with pathologically confirmed NSCLC in advanced stage (III or IV) received treatment with oral erlotinib at the daily dose of 150 mg, and the treatment was discontinued until intolerance of the side effects or the occurrence of disease progression. The clinical effect and adverse side effects of erlotinib were further observed, and the association between clinical characteristics and the response to erlotinib was also analyzed.

RESULTSAmong the 72 patients, 1 patient achieved complete remission, 8 patients had partial remission, 10 had stable disease, and 7 had progressive disease, with a disease control rate of 72.22%. After a median follow-up time of 17 months (4 to 32 months), the median survival time was 14.5 months (6.5-28.3 months), and the median time to progression was 10.6 months (5-16.5 months). Erlotinib resulted in a significantly higher rate of favorable response in female, non-smoking patients with adenocarcinoma than in male, smoking patients with squamous carcinoma (P<0.05). The occurrence of skin rash was not associated with the response to erlotinib in these patients (P>0.05). The most common drug-related adverse events included skin rash, diarrhea, hepatic dysfunction (GPT elevation), nausea and vomiting, but mostly mild and well tolerable.

CONCLUSIONErlotinib is safe and effective in the treatment of elderly patients with advanced NSCLC.

Adenocarcinoma ; drug therapy ; Aged ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Carcinoma, Squamous Cell ; drug therapy ; Disease-Free Survival ; Erlotinib Hydrochloride ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Neoplasm Staging ; Quinazolines ; adverse effects ; therapeutic use

OBJECTIVETo explore the efficacy and side effects of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC).

METHODSThe efficacy and side effects of icotinib hydrochloride in treatment of 59 cases with stage IV NSCIC and followed-up from March 2009 to January 2012 were retrospectively analyzed.

RESULTSTwenty seven patients (45.8%) showed partial response (PR), 17 patients (28.8%) achieved SD, and 15 (25.4%) had progressive disease. The objective response rate (ORR) was 45.8% (27/59), and disease control rate (DCR) was 74.6% (44/59). Among the 23 patients with EGFR mutation, ORR was 73.9% (17/23), and DCR was 95.7% (22/23). Thirty six patients (61.0%) achieved remission of symptoms to varying degrees. The main symptoms relieved were cough, asthmatic suffocating, pain and hoarseness. The major adverse events were mild skin rash (35.6%) and diarrhea (15.3%). Others were dry skin, nausea and stomach problems. The efficacy of icotinib hydrochloride were related to the ECOG performance status, smoking history, EGFR mutation and rash significantly (P < 0.05).

CONCLUSIONSMonotherapy with icotinib hydrochloride is effective and tolerable for patients with advanced NSCLC, especially with EGFR mutation.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; pathology ; Crown Ethers ; adverse effects ; therapeutic use ; Diarrhea ; chemically induced ; Disease Progression ; Exanthema ; chemically induced ; Exons ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Quinazolines ; adverse effects ; therapeutic use ; Receptor, Epidermal Growth Factor ; genetics ; Remission Induction ; Retrospective Studies ; Survival Rate

We report a case of vortex keratopathy in a patient treated with vandetanib for non-small cell lung cancer (NSCLC). A 44-year-old female who underwent two cycles of chemotherapy for NSCLC complained of visual blurring in both eyes after the initiation of vandetanib, an anti-epidermal growth factor receptor (EGFR) and anti-vascular endothelial growth factor receptor 2 protein tyrosine kinase inhibitor. On ophthalmic examination, visual acuities were 20 / 20 OU and, with the exception of diffuse vortex keratopathy in both eyes, other findings were unremarkable. Vandetanib is believed to have caused vortex keratopathy in this patient. Anti-EGFR properties affecting normal corneal epithelial cell migration and wound healing or drug associated metabolite deposition, which is the case in numerous drug-associated vortex keratopathies, may be possible underlying mechanisms in the formation of this corneal complication.
Adult ; Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology ; Cornea/drug effects/*pathology ; Corneal Diseases/*chemically induced/diagnosis ; Diagnosis, Differential ; Dose-Response Relationship, Drug ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/*drug therapy/pathology ; Microscopy, Acoustic ; Piperidines/administration & dosage/*adverse effects ; Quinazolines/administration & dosage/*adverse effects ; Visual Acuity