Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) have elicited curative effects on patients with advanced non-small celllung cancer and with activating mutations in the EGFR gene. However, acquired resistance to EGFR-TKIs is eventually developed after an initial response is induced;as such, patients with acquired resistance must be treated with more ef-fective strategies to delay or possibly overcome the resistance. This article reviews available data on the treatment of patients who have failed to respond to EGFR-TKI.

Objective To evaluate the impact of comorbidity and age on the tolerance of firstline single-agent chemotherapy in elderly patients with advanced non-small cell lung cancer(NSCLC).Methods Clinical data of 61 elderly patients with advanced NSCLC(aged over 70 years,median age 72 years) receiving first-line single agent chemotherapy were retrospectively analyzed in this study.Performance status(PS) between 0-1 score was in 52 patients,PS 2 score in the other 9 patents.Patients were treated with gemcitabine or docitaxel as the first line chemotherapy,and the median number of chemotherapy cycles was 3.4.Comorbidity was assessed by Charlson comorbidity index (CC1).Patients with CCI equal to 0 were classified as non comorbidity group(n=26),and patients with CCI≥1 were classified as comorbidity group(n=35).Adverse reactions were graded by using the criteria of NCI-CTC v3.0.Results Age and PS could not predict adverse effects of grade 3 or 4.The incidence of hematologic toxicity of grade 3 or 4 was higher in comorbidity group than in noncomorbidity group(40.0％ vs.15.4％,x2 =4.36,P=0.037).The incidences of febrile neutropenia,non hematologic toxicity of grade 3 or 4 and treatment suspension were higher in comorbidity group than in non-comorbidity group.The most common types of comorbidity were diabetes and chronic pulmonary disease.The incidence of non-hematologic toxicity of grade 3 or 4 was increased in patients with chronic pulmonary disease as compared with patients without chronic pulmonary disease(41.4 ％vs.11.5％,x2=6.061,P=0.032).Conclusions The incidences of adverse reactions,especially hematologic toxicity of grade 3 or 4 are significantly increased in patients with comorbidity after singleagent chemotherapy.Evaluation of comorbidity before treatment is helpful to predict the tolerance of single-agent chemotherapy in elderly NSCLC patients.

About half of the elderly patients with advanced non-small cell lung cancer (NSCLC) can not receive effective treatment due to the decreased organ function and complication. Monotherapies using the third generation new drugs have became a standard first-line therapy for NSCLC, as documented by prospective phase 3 clinical trials. Combined chemotherapies that contain platin and single agent are considered optional first- and second-line treatment for patients with good physical performance and few complication. The epidermal growth factor receptor tyrosine kinase inhibitors may become a key therapeutic agent,while the role of anti-vascular endothelial growth factor monoclonal antibody remains unclear. More prospective phase 3 targeting at the elderly patients should be designed and conducted.
Aged ; Antibodies, Monoclonal ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Humans ; Lung Neoplasms ; drug therapy ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors

BACKGROUND: Paraquat (PQ) is a world-wide used herbicide and also a type of common poison for suicide and accidental poisoning. Numerous studies have proved that the concentration of serum PQ plays an important role in prognosis. Spectrophotometry, including common spectrophotometry and second-derivative spectrophotometry, is commonly used for PQ detection in primary hospitals. So far, lack of systematic research on the reliability of the method and the correlation between clinical features of patients with PQ poisoning and the test results has restricted the clinical use of spectrophotometry. This study aimed to evaluate the reliability and value of spectrophotometry in detecting the concentration of serum PQ. METHODS: The wavelengths for detecting the concentration of serum PQ by common and second-derivative spectrophotometry were determined. Second-derivative spectrophotometry was applied to detect the concentration of serum PQ. The linear range and precision for detection of PQ concentration by this method were confirmed. The concentration of serum PQ shown by second-derivative spectrophotometry and HPLC were compared in 8 patients with PQ poisoning. Altogether 21 patients with acute poisoning 4 hours after PQ ingestion treated in the period of October 2008 to September 2010 were retrospectively reviewed. The patients were divided into higher and lower than 1.8 μg/mL groups based on their concentrations of serum PQ measured by second-derivative spectrophotometry on admission. The severity of clinical manifestations between the two groups were analyzed with Student's t test or Fisher's exact test. RESULTS: The absorption peak of 257 nm could not be found when common spectrophotometry was used to detect the PQ concentration in serum. The calibration curve in the 0.4–8.0 μg/mL range for PQ concentration shown by second-derivative spectrophotometry obeyed Beer's law with r=0.996. The average recovery rates of PQ were within a range of 95.0％ to 99.5％, relative standard deviation (RSD) was within 1.35％ to 5.41％ (n=6), and the lower detection limit was 0.05 μg/mL. The PQ concentrations in serum of 8 patients with PQ poisoning shown by second-derivative spectrophotometry were consistent with the quantitative determinations by HPLC (r=0.995, P<0.0001). The survival rate was 22.2％ in patients whose PQ concentration in serum was more than 1.8 μg/mL, and the incidences of acidosis, oliguria and pneumomediastinum in these patients were 55.6％, 55.6％and 77.8％, respectively. These clinical manifestations were different significantly from those of the patients whose PQ concentration in serum was less than 1.8 μg/mL (P<0.05). CONCLUSIONS: For common spectrophotometry, the wavelength at 257 nm was not suitable for detecting serum PQ as no absorbance was shown. Second-derivative spectrophotometry was reliable for detecting serum paraquat concentration. Serum PQ concentration detected by second-derivative spectrophotometry could be used to predict the severity of clinical manifestations of patients with PQ poisoning, and PQ content higher than 1.8 μg/mL 4 hours after ingestion could be an important predictive factor for poor prognosis.

Adolescent ; Child ; Child, Preschool ; Cytomegalovirus Infections ; complications ; Female ; Humans ; Kidney Diseases ; etiology ; Kidney Glomerulus ; pathology ; Male

Adult ; Female ; Helicobacter Infections ; complications ; Helicobacter pylori ; Humans ; Hyperemesis Gravidarum ; etiology ; Pregnancy

OBJECTIVETo retrospectively analyze the treatment outcomes and side effects of childhood acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) or ATRA + arsenic trioxide (As2O3).

METHODSFrom 1992 to 2006, 45 patients with newly diagnosed APL were enrolled. All of them were PML-RAR alpha positive. 24 patients were induced with ATRA (group A) and 21 with ATRA + As2O3 (group B). The remission rate and side effects were observed.

RESULTS1) 19 (79.2%) patients in group A achieved CR, while 21(100%) patients in group B achieved CR. The CR rate in group A was lower than that in group B (P=0.027). 2) The recovery time of coagulation parameters and PLT count in group B was shorter than that in group A. 3) The overall survival (OS) and event-free survival(EFS) in group A were 77.8% and 66.9% at 41 months of follow-up, and in group B were 100% and 100% respectively at 34 months of followup. Group A had a significant lower EFS (P=0.0357)than group B. 4) The time of PML-RAR alpha fusion gene converting to negative in group A was longer (P=0.026) than that in group B.

CONCLUSIONSATRA + As2O3 for patients with newly diagnosed childhood APL is a feasible treatment with higher CR rate, less side effects and longer long-term survival.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; Male ; Oncogene Proteins, Fusion ; genetics ; Oxides ; administration & dosage ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Tretinoin ; administration & dosage

BACKGROUNDbevacizumab is a humanized recombinant vascular endothelial growth factor (VEGF) monoclonal antibody, which specifically binds to VEGF and inhibits tumor cell growth, proliferation and metastasis. We aimed to investigate the safety and pharmacokinetics of bevacizumab in Chinese patients with advanced cancer.

METHODSThirty-nine Chinese patients with metastatic or relapsed cancers who failed prior therapy were enrolled in this phase I study of bevacizumab. Bevacizumab was infused by a calculated pump at doses from 5 mg/kg to 15 mg/kg in 90 minutes. Patients underwent serial pharmacokinetic evaluations. Patients that received at least one infusion of bevacizumab were included in the safety study.

RESULTSThirty-five patients finished all 5 infusions following protocol. One patient withdrew after 3 infusions due to grade 3 proteinuria. Common adverse events possibly related to the study drug were proteinuria (17/39, 43.6%), hypertension (13/39, 33.3%), gingival bleeding (7/39, 17.9%), epistaxis (6/39, 15.4%), pharyngeal inflammation (6/39, 15.4%), fatigue (6/39, 15.4%) and stomatitis (4/39, 10.3%). Bevacizumab pharmacokinetics was linear within the range of 5 mg/kg q2w--10 mg/kg q2w and 15 mg/kg q3w. CL (clearance), Vd (volume of distribution at elimination) and Vss (volume of distribution at steady state) were similar after single and multiple doses at 5, 10 and 15 mg/kg.

CONCLUSIONSBevacizumab is well tolerated in Chinese patients. No unexpected adverse events were observed. There is no racial difference in the pharmacokinetics.

Adult ; Aged ; Angiogenesis Inhibitors ; adverse effects ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal ; adverse effects ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Asian Continental Ancestry Group ; Bevacizumab ; Female ; Humans ; Male ; Middle Aged ; Neoplasms ; drug therapy

OBJECTIVETo study the clinical features and etiological spectrum of pancytopenia in children.

METHODSThe clinical data of 174 children with pancytopenia between September 2003 and January 2010 were retrospectively reviewed.

RESULTSPale face was the most common clinical manifestation (147 cases, 84.5%), followed by bleeding (87 cases, 50.0%) and fever (41 cases, 23.6%). Mild to moderate anemia, severe thrombocytopenia and mild leucopenia were common in complete blood count. Of the 174 children, pancytopenia was attributed to hematopoietic system diseases in 155 cases (89.1%) and non-hematopoietic system diseases (virus infections, systemic lupus erythematosus, hypersplenism and neuroblastoma) in 6 cases (3.4%). Aplastic anemia (91 cases, 52.3%) was the most common cause of pancytopenia, followed by myelodysplastic syndrome (37 cases, 21.3%), acute leukemia and other hematological tumours (11 cases, 6.3%) and hemophagocytic syndrome (6 cases, 3.4%). The cause of pancytopenia was not identified in 13 cases (7.5%).

CONCLUSIONSAnemia, bleeding and fever are the main clinical manifestations of pancytopenia in children. Pancytopenia is mostly caused by aplastic anemia in children. Myelodysplastic syndrome, hematological tumours and hemophagocytic syndrome are also the common causes.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Pancytopenia ; blood ; diagnosis ; etiology

OBJECTIVETo explore the mechanism of acupuncture in treatment of spinal cord injury (SCI).

METHODSAdult Wistar rats were used to make SCI model by Allen's method. The SCI rats were treated with electroacupuncture (EA) at acupoints of the Governor Vessel for 3 days, 1 week, 2 weeks or 4 weeks. Normal group and spinal cord injury group were used as controls. The number and morphology of astrocytes in each group were investigated by electron microscope, immunohistochemistry and in situs hybridization methods. The expression of glial fibroblast acid protein (GFAP) mRNA in the injured spinal cord was detected by reverse transcription polymerase (RP-PCR).

RESULTSThe mitochondria and ribosomes of astrocytes in the EA group increased. The number of astrocytes increased after SCI, in gray matter being more than that in the white matter, in the caudal being more than that in the rostral. The expression of GFAP mRNA in the EA group was significantly lower than that in the control group.

CONCLUSIONElectroacupuncture can inhibit the reactive proliferation of the astrocytes after spinal cord injury and prevent formation of the glial scar.

Animals ; Astrocytes ; Electroacupuncture ; Humans ; Rats, Sprague-Dawley ; Rats, Wistar ; Spinal Cord Injuries ; therapy