Chemotherapy is expected to play an important role in the treatment of pancreatic cancer because most of pancreatic cancers are being discovered at locally advanced or metastatic stages and recurrence rate is high even after the curative resection. Gemcitabine is a key agent for the first-line therapy of advanced pancreatic cancer. It can enhance the quality of life and prolong the survival of patients. Combination of erlotinib or capecitabine with gemcitabine showed a marginal survival benefit over single-agent gemcitabine. If patient's performance state is good, gemcitabine-based platinum combination therapy showed overall survival benefit compared with gemcitabine monothrapy. If the first-line palliative chemotherapy fails, 5-FU, capcitabine, or tegafur with or without combination can be used as the second-line agents. Adjuvant chemotherapy using 5-FU or gemcitabine after curative resection has overall survival benefit. However, neoadjuvant chemotherapy has not been proven to be effective in the treatment of pancreatic cancer.
Antimetabolites/therapeutic use ; Antimetabolites, Antineoplastic/therapeutic use ; Chemotherapy, Adjuvant ; Deoxycytidine/analogs & derivatives/therapeutic use ; Fluorouracil/analogs & derivatives/therapeutic use ; Humans ; Pancreatic Neoplasms/*drug therapy ; Protein Kinase Inhibitors/therapeutic use ; Quinazolines/therapeutic use

OBJECTIVETo evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).

METHODSPatients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.

RESULTSA total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).

CONCLUSIONAnagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.

Humans ; Hydroxyurea ; administration & dosage ; therapeutic use ; Platelet Aggregation Inhibitors ; administration & dosage ; therapeutic use ; Platelet Count ; Quinazolines ; administration & dosage ; therapeutic use ; Thrombocythemia, Essential ; drug therapy ; Treatment Outcome

BACKGROUNDGefitinib is widely used in patients with advanced non-small-cell lung cancer (NSCLC), in whom chemotherapy had failed. Previous trials reported inconsistent findings regarding the efficacy of gefitinib on overall survival (OS) and progression free survival (PFS). This study was to evaluate the effects of chemotherapy plus gefitinib versus chemotherapy alone on survival of patients with NSCLC.

METHODSWe systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings for relevant literature. Randomized controlled trials (RCTs) comparing chemotherapy with and without gefitinib in the treatment of patients with advanced NSCLC were included in our analysis. The primary endpoints were OS and PFS.

RESULTSOf 182 relevant studies, 12 were included in the final analysis, which consisted of 6844 patients with NSCLC. Overall, we noted that gefitinib therapy had an 8% improvement in the OS as compared to the gefitinib-free therapy, but this difference was not statistically significant (HR, 0.92; 95% CI: 0.85-1.00; P=0.051). Furthermore, gefitinib therapy had significantly longer PFS compared to gefitinib-free therapy (HR, 0.72; 95% CI 0.60-0.87, P=0.001). Patients receiving gefitinib therapy also had a more frequent objective response rate (ORR) than the control arm (OR, 2.51; 95% CI, 1.67-3.78, P < 0.001). Rashes, diarrhea, dry skin, pruritus, paronychia, and abnormal hepatic function were more frequent in the gefitinib therapy group.

CONCLUSIONSTreatment with gefitinib had a clear effect on PFS and ORR, and it might contribute considerably to the OS. Furthermore, there was some evidence of benefit for gefitinib therapy among patients with adenocarcinoma.

Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Humans ; Lung Neoplasms ; drug therapy ; Quinazolines ; therapeutic use ; Randomized Controlled Trials as Topic

Aged ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Disseminated Intravascular Coagulation ; chemically induced ; Female ; Humans ; Quinazolines ; adverse effects ; therapeutic use

We described 3 cases of advanced bronchioloalveolar carcinoma (BAC), in whom once-daily treatment with 250 mg Gefitinib (Iressa) demonstrated remarkable antitumor effects. Gefitinib may produce dramatic clinical responses when administered to patients with poor performance status who had received heavy platinum/docetaxel-based prior chemotherapy.
Adenocarcinoma, Bronchiolo-Alveolar ; drug therapy ; Aged ; Antineoplastic Agents ; therapeutic use ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Middle Aged ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors

Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; metabolism ; Quinazolines ; therapeutic use

Molecule-targeting agents inhibit the proliferation of tumor cells by the molecular biological differences between tumor cells and normal cells, and finally kill tumor cells. This article introduces several molecule-targeting agents that are currently under clinical trials now.
Angiogenesis Inhibitors ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Erlotinib Hydrochloride ; Humans ; Lung Neoplasms ; drug therapy ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors

OBJECTIVETo guide the optimal selection among first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in clinical practice. This review attempted to provide a thorough comparison among three first-generation EGFR-TKIs, namely icotinib, erlotinib, and gefitinib, with regard to their molecular structure, pharmacokinetic parameters, clinical data, adverse reactions, and contraindications.

DATA SOURCESAn electronic literature search of the PubMed database and Google Scholar for all the available articles regarding gefitinib, icotinib, and erlotinib in the English language from January 2005 to December 2014 was used.

STUDY SELECTIONThe search terms or keywords included but not limited to "lung cancer", "nonsmall cell lung cancer (NSCLC)", "epidemiology", "EGFR", "TKIs", and "optimal selection ".

RESULTSAs suggested by this review, even though the three first-generation EGFR-TKIs share the quinazoline structure, erlotinib had the strongest apoptosis induction activity because of its use of a different side-chain. The pharmacokinetic parameters indicated that both erlotinib and icotinib are affected by food. The therapeutic window of erlotinib is narrow, and the recommended dosage is close to the maximum tolerable dosage. Icotinib enjoys a wider therapeutic window, and its concentration in the blood is within a safe dosage range even if it is administered with food. Based on multiple large-scale clinical trials, erlotinib is universally applied as the first-line treatment. In marked contrast, icotinib is available only in China as the second- or third-line therapeutic approach for treating advanced lung cancer. In addition, it exhibits a similar efficacy but better safety profile than gefitinib.

CONCLUSIONSAlthough there is a paucity of literature regarding whether icotinib is superior to erlotinib, its superior toxicity profile, noninferior efficacy, and lower cost indicate that it is a better alternative for Chinese patients living with advanced NSCLC.

Carcinoma, Non-Small-Cell Lung ; drug therapy ; Crown Ethers ; therapeutic use ; Erlotinib Hydrochloride ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; Quinazolines ; therapeutic use ; Treatment Outcome

Acrylamides ; therapeutic use ; Aged ; Aniline Compounds ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; Crown Ethers ; therapeutic use ; ErbB Receptors ; genetics ; metabolism ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Mutation ; genetics ; Quinazolines ; therapeutic use

Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) have been reported to be related to certain clinical characteristics (i.e., female, non-smokers with adenocarcinoma) and gefitinib responsiveness. This exploratory analysis was performed to determine the incidence of EGFR mutations in male smokers with squamous cell carcinoma, who were treated with EGFR tyrosine kinase inhibitor, gefitinib. Sixty-nine Korean NSCLC patients were treated with gefitinib in a prospective study. For a subset of 20 male patients with squamous cell carcinoma and a history of smoking, pretreatment tumor tissue samples were obtained and analyzed for EGFR mutations (exons 18 to 21). EGFR mutations were found in 3 (15%) patients, including in-frame deletions within exon 19 (n=2) and L858R missence mutation in exon 21 (n=1). These 3 patients with EGFR mutations responded to gefitinib, whereas only one of remaining 17 patients with wild-type EGFR achieved clinical response. Trend toward longer progression-free (5.8 vs. 2.4 months; P=0.07) was noted in patients with EGFR mutations compared to those with wild-type EGFR. Although male smokers with squamous cell carcinoma have not been considered ideal candidates for gefitinib treatment, significant incidence of EGFR mutations was observed. The molecular markers should be considered to predict clinical benefits from gefitinib.
Adult ; Aged ; Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/*genetics ; Humans ; Lung Neoplasms/*genetics ; Male ; Middle Aged ; *Mutation ; Protein Kinase Inhibitors/therapeutic use ; Quinazolines/therapeutic use ; Receptor, Epidermal Growth Factor/*genetics ; *Smoking ; Treatment Outcome