PURPOSE: Erlotinib-gemcitabine combined chemotherapy is considered as the standard treatment for unresectable pancreatic cancer. This study aimed to determine the clinical factors associated with response to this treatment. MATERIALS AND METHODS: This retrospective study included 180 patients with unresectable pancreatic cancer who received ≥2 cycles of gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy between 2006 and 2014. "Long-term response" was defined as tumor stabilization after >6 chemotherapy cycles. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 3.9 and 8.1 months, respectively. On univariate analysis, liver metastasis (p=0.023) was negatively correlated with long-term response. Locally advanced stage (p=0.017), a history of statin treatment (p=0.01), and carcinoembryonic antigen levels <4.5 (p=0.029) had a favorable effect on long-term response. On multivariate analysis, a history of statin treatment was the only independent favorable factor for long-term response (p=0.017). Prognostic factors for OS and PFS were significantly correlated with liver metastasis (p=0.031 and 0.013, respectively). A history of statin treatment was also significantly associated with OS after adjusting for all potential confounders (hazard ratio, 0.48; 95% confidence interval, 0.26-0.92; p=0.026). CONCLUSION: These results suggest that statins have a favorable effect on "long-term response" to gemcitabine-erlotinib chemotherapy in unresectable pancreatic cancer patients. Statins may have a chemoadjuvant role in stabilizing long-term tumor growth.
Adenocarcinoma/*drug therapy/secondary ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Deoxycytidine/administration & dosage/analogs & derivatives ; Disease-Free Survival ; Erlotinib Hydrochloride/administration & dosage ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic Neoplasms/*drug therapy/pathology ; Retrospective Studies ; Survival Rate ; Young Adult

OBJECTIVETo explore the radiosensitizing effect of erlotinib on human lung adenocarcinoma cell line A549 cells and the related mechanisms.

METHODSThe inhibitory effect of erlotinib on A549 cells was assessed by MTT assay, and its IC50 concentration was calculated. The radiosensitization was evaluated by the method of clone forming assay. Flow cytometry was used to analyze the effect of erlotinib on cell cycle and apoptosis.

RESULTSThe growth of A549 cells was inhibited after the cells were exposed to erlotinib for 48 hours. Moreover, the inhibitory rates increased with the increase of erlotinib concentrations, and IC50 was 19.26 µmol/L. In contrast to the irradiation alone group, the survival rates of the cells in erlotinib plus irradiation groups decreased, and erlotinib enhanced the radiosensitivity of the A549 cells. This effect was further increased as cells were exposed to erlotinib for a longer time. In the irradiation alone group and the two groups exposed to erlotinib for 24 hours and 48 hours before irradiation, D0 values were 3.01 Gy, 2.58 Gy and 2.45 Gy respectively, and Dq values were 2.16 Gy, 1.94 Gy and 1.61 Gy, respectively. In the last two groups, SERD0 values were 1.17 and 1.23, respectively. The flow cytometry analysis showed that erlotinib induced G2/M phase arrest and increased the apoptosis rate in A549 cells. With the increase of exposure time, the effects were more significant.

CONCLUSIONSErlotinib inhibits the A549 cell growth and enhances the radiosensitivity of A549 cells in vitro. The radiosensitizing mechanisms might be related to inhibiting repair of sublethal injury and inducing G2/M phase arrest and apoptosis.

Adenocarcinoma ; pathology ; Apoptosis ; drug effects ; radiation effects ; Cell Cycle ; drug effects ; radiation effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; radiation effects ; Dose-Response Relationship, Drug ; Erlotinib Hydrochloride ; Humans ; Lung Neoplasms ; pathology ; Particle Accelerators ; Quinazolines ; administration & dosage ; pharmacology ; Radiation Tolerance ; drug effects ; Radiation-Sensitizing Agents ; administration & dosage ; pharmacology

For patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the relationship between the dose or duration of treatment with tyrosine kinase inhibitor (TKI) and overall survival remains unclear. Here, we analyzed clinical data of 39 patients who were diagnosed with EGFR mutation-positive non-small cell lung cancer and treated with TKI, but subsequently died. Several parameters were measured in this study: overall survival; first, second, and overall TKI therapy durations; first TKI intensity (actual dose/normal dose); and TKI rate (overall TKI therapy duration/overall survival). The response rate to TKI therapy was 50%, and the median survival was 553 days. After TKI therapy failed, 38.5% patients were re-challenged with TKI. We observed a moderate relationship [r = 0.534, 95% confidential interval (CI) = 0.263 to 0.727, P < 0.001] between overall TKI therapy duration and overall survival. However, we found no relationship between overall survival and first TKI intensity (r = 0.073, 95% CI = -0.380 to 0.247, P = 0.657) or TKI rate (r = 0.0345, 95% CI = -0.284 to 0.346, P = 0.835). Non-small cell lung cancer patients with mutation-positive tumors remained on TKI therapy for, on average, 33% of the overall survival time. These findings suggest that patients with EGFR mutation-positive tumors should not stick to using TKIs.
Aged ; Aged, 80 and over ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; genetics ; Dose-Response Relationship, Drug ; Erlotinib Hydrochloride ; Female ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Protein Kinase Inhibitors ; administration & dosage ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Quinazolines ; administration & dosage ; therapeutic use ; Receptor, Epidermal Growth Factor ; genetics ; Survival Rate

OBJECTIVEEpidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) such as gefitinib and erlotinib are used as standard 2(nd)/3(rd) line therapy in previously treated advanced non-small cell lung cancer (NSCLC). However, the optimal treatment for patients who experienced disease progression after chemotherapy and EGFR-TKI is unclear. The aim of this study was to explore the efficacy and safety of a salvage chemotherapy in advanced NSCLC patients who failed the previous treatment of platinum-based chemotherapy and EGFR-TKI.

METHODSClinicopathological data of 55 cases of advanced NSCLC patients who failure of first-line platinum-based chemotherapy and subsequent treatment with TKI were collected and analyzed. The patients were of PS = 0-2, and with normal vital organ function. Patients received salvage chemotherapy until disease progression or unacceptable toxicity or the patient refused to continue receiving treatment. A chart review assessed the key outcomes including the objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS).

RESULTSFifty-five patients were enrolled in this study from march 2007 to october 2009. The median age of patients was 55 years (range: 34 - 72), 60.0% were males, PS 0-1 patients were 65.5%, stage IV patients were 100%; 34.5% had a TKI treatment duration ≥ 6 months. Twenty-four patients received pemetrexed as salvage chemotherapy, 21 received docetaxal and 10 had other chemotherapy. All patients were evaluable for efficacy. Among them, 7 (12.7%) patients achieved PR, 21 (38.2%) patients SD, and 27 (49.1%) patients PD, with ORR of 12.7% and DCR of 50.9%. The median follow-up duration was 5.5 months, and the median PFS was 2.0 months. The ORR and PFS were not significantly related with gender, PS and chemotherapy regimens (all P > 0.05), but patients with EGFR-TKI treatment ≥ 6 months achieved a significantly better ORR and DCR than those < 6 months (ORR: 21.1% vs. 8.3%, P = 0.012; DCR: 73.3% vs. 38.9%, P = 0.017), mPFS was significant longer in the patients received ≥ 6 months of EGFR-TKI (4.5 vs. 2.0 months, P = 0.008). The toxicity was acceptable and there were no treatment-related deaths.

CONCLUSIONAdvanced NSCLC patients failed with the previous treatment of first-line platinum-based chemotherapy and EGFR-TKI may benefit from salvage chemotherapy, especially in patients who received ≥ 6 months of EGFR-TKI. The toxicity of the salvage chemotherapy is acceptable.

Adult ; Aged ; Antimetabolites, Antineoplastic ; adverse effects ; therapeutic use ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Disease-Free Survival ; Erlotinib Hydrochloride ; Female ; Follow-Up Studies ; Glutamates ; adverse effects ; therapeutic use ; Guanine ; adverse effects ; analogs & derivatives ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia ; chemically induced ; Pemetrexed ; Platinum ; administration & dosage ; Protein Kinase Inhibitors ; therapeutic use ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; therapeutic use ; Remission Induction ; Salvage Therapy ; Taxoids ; adverse effects ; therapeutic use ; Treatment Failure

OBJECTIVETo evaluate the efficacy,clinical benefits and toxicities of gemcitabine combined with erlotinib for advanced pancreatic cancer.

METHODClinical data of 20 patients with advanced pancreatic cancer treated with gemcitabine 1000 mg/m2 on day 1 and day 8 (repeated every 21 days) plus erlotinib 100-150 mg/d at Peking Union Medical College Hospital was reviewed retrospectively.

RESULTSNo patient achieved complete remission or partial remission, 11 patients (55%) had stable disease, and 9 patients (45%) experienced disease progression. The disease control rate was 55%, and clinical benefit rate was 30%. The median progression free survival was 4.0 months, and the median overall survival was 8 months. The total incidence of hematologic toxicity was 70%, including 15% of grade 3-4 leucopenia and 5% of grade 3-4 thrombocytopenia. Eleven patients (55%) had rash, which were all grade 1-2. One patient had grade 2 diarrhea and five had grade 1 transaminase elevation. No chemotherapy-related death occurred.

CONCLUSIONSGemcitabine combined with erlotinib is an effective regimen for pancreatic cancer with good clinical tolerance. The most common adverse events are hematologic toxicities and rash.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Erlotinib Hydrochloride ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms ; drug therapy ; Quinazolines ; administration & dosage ; Retrospective Studies ; Treatment Outcome

BACKGROUND AND OBJECTIVEEpidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has been widely used as the second- and third-line therapy in patients with advanced non-small cell lung cancer (NSCLC). However, its effect in the first-line treatment is unclear. The aim of this study was to evaluate the efficacy and safety of EGFR-TKI as first-line therapy.

METHODSThe clinical characteristics, responses rate, disease control rate and overall survival were retrospectively analyzed in 77 chemonaive patients with advanced NSCLC. All of the patients received oral gefitinib (250 mg/d) or erlotinib (150 mg/d) until disease progression or unacceptable toxicity occurrence.

RESULTSThe overall response rate was 33.8% and the disease control rate was 68.8%. The median progression-free survival and the median survival time were 6.0 months and 8.9 months, respectively. One-year survival rate was 61.4%. Responses correlated significantly with histology, PS score, smoking history, skin rash, EGFR mutations and serum CEA. Histology and skin rash were the independent predictors of survival. Common toxicities were skin rash and mild diarrhea. EGFR-TKI could improve the clinical symptoms and the quality of life.

CONCLUSIONEGFR-TKI is effective and well tolerated as first-line therapy in patients with advanced NSCLC.

Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; mortality ; Erlotinib Hydrochloride ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Quinazolines ; administration & dosage ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Retrospective Studies ; Young Adult

OBJECTIVE: This study was designed to prove simultaneously blocking both EGFR and COX-2-mediated pathways may be an efficient means of inhibiting cancer cell growth in NPC. METHOD: A combination of tarceva (EGFR-selective tyrosine kinase inhibitors) with celecoxib (Cox-2 inhibitor) was studied on its effects on cell growth, cell cycle progression, apoptosis and protein expression in CNE-2 cell lines by cell growth assay, flow cytometric analysis assay and Western blotting. RESULT: (1) The inhibition rate of cell growth was higher in the group treated with a combination of two agents than that the sum of rates of the two groups treated with only one agent (P < 0.05). (2) The combination of tarceva with celecoxib significantly induced G1 arrest (P < 0.05), but did not increase apoptosis rate (P > 0.05). (3) The group of combination showed less expressions of p-EGFR and COX-2 than any other group. CONCLUSION Simultaneously blocking EGFR and COX-2 mediated pathways would significantly inhibit the growth of CNE-2 cell line, increase G1 arrest and reduce the expression levels of p-EGFR and COX-2.
Apoptosis ; Celecoxib ; Cell Division ; Cyclooxygenase 2 ; metabolism ; ErbB Receptors ; metabolism ; Erlotinib Hydrochloride ; Humans ; Pyrazoles ; administration & dosage ; pharmacology ; Quinazolines ; administration & dosage ; pharmacology ; Signal Transduction ; Sulfonamides ; administration & dosage ; pharmacology ; Tumor Cells, Cultured

OBJECTIVETo investigate the efficacy and side effect of erlotnib for refractory patients with advanced non-small cell lung cancer (NSCLC) failed to previous chemotherapy.

METHODSTwelve patients with chemo-refractory NSCLC were enrolled into this study. Erlotnib was administered at a dose of 150 mg orally once a day for a month. The assessment was carried out every month by intensive clinical observation and monthly CT scan until disease progression or intolerable toxicity occurred.

RESULTSAll the 12 patients were evaluable. The response rate including complete and partial responses (CR and PR) was 25.0% (3/12). The disease control rate including complete, partial response and stable disease (CR, PR and NC) was 58.3% (7/12). The clinical benefit rate was 41.7% (5/12). The main side effects included skin rash and diarrhea. No patient was withdrawn from the treatment due to intolerable toxicities.

CONCLUSIONErlotnib is effective and tolerable in the treatment of patients with advanced NSCLC failed to previous chemotherapy.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoembryonic Antigen ; blood ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; Diarrhea ; chemically induced ; Erlotinib Hydrochloride ; Exanthema ; chemically induced ; Female ; Humans ; Lung Neoplasms ; blood ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Quality of Life ; Quinazolines ; adverse effects ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Remission Induction ; Treatment Failure ; Young Adult

Antibodies, Monoclonal ; administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; administration & dosage ; Benzamides ; Cetuximab ; Drug Delivery Systems ; methods ; Drug Design ; Erlotinib Hydrochloride ; Humans ; Imatinib Mesylate ; Immunologic Factors ; administration & dosage ; Neoplasms ; drug therapy ; Palliative Care ; methods ; Piperazines ; administration & dosage ; Pyrimidines ; administration & dosage ; Quinazolines ; administration & dosage ; Signal Transduction

Benzamides ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Drug Delivery Systems ; Erlotinib Hydrochloride ; Humans ; Imatinib Mesylate ; Lung Neoplasms ; drug therapy ; Piperazines ; administration & dosage ; Pyrimidines ; administration & dosage ; Quinazolines ; administration & dosage ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors