High levels of Phosphatase and Tensin Homolog Expression Predict Favorable Prognosis in Patients with Non-small Cell Lung Cancer.

The prognostic role of phosphatase and tensin homolog (PTEN) in non-small cell lung cancer (NSCLC) has been controversial. In this study, levels of PTEN expression were investigated in NSCLC patients and their prognostic value in NSCLC was assessed. PTEN expression in tumor tissues from 68 NSCLC patients was analyzed using immunohistochemistry and confocal microscopy. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. NSCLC patients classified as expressers of high levels of PTEN (n = 46) had better prognoses than those classified as expressers of low levels (mean survival 17.1 vs. 12.9 months, log rank P = 0.038). In patients with adenocarcinoma (AC), high PTEN expression (n = 9) was associated with significantly longer survival than low PTEN expression (mean survival 23.50 vs. 15.54 months, log rank P = 0.043). High levels of PTEN expression resulted in 43 % reduction in risk for all NSCLC patients (HR 0.57, 95 % CI 0.33-0.98, P = 0.041). PTEN expression and clinical stage remained significantly associated with survival after adjustment for age, sex, and tumor type (HR 0.56, 95 % CI 0.32-0.99; P = 0.048; HR 0.54, 95 % CI 0.36-0.97; P = 0.045). No significant difference in continuous PTEN expression levels was observed among groups with different clinical or pathological characteristics (P > 0.17). When levels of PTEN expression were binarized using the optimal cut-point, higher levels of PTEN expression were observed in patients with T1/T2 than in those with T3/T4 (80 and 58 %, respectively, P = 0.049) and in patients with AC than in those with squamous-cell carcinoma (78 and 58 %, respectively, P = 0.08). No significant difference in binarized PTEN expression levels was found among groups with any other clinical/pathologic characteristic (P > 0.28). Our results suggest that high levels of PTEN expression may be favorable prognostic markers in NSCLC patients.

Favorable response to icotinib in a lung cancer patient with a special mutation at exon 19 of epidermal growth factor receptor.

Many studies have illustrated that two types of mutation - deletions in exon 19 and a point mutation in exon 21 (L858R) - have been reported to comprise up to 90% of all activating epidermal growth factor receptor (EGFR) mutations. A point mutation at exon 19 is a rare mutation, and to date there have been no reports investigating the sensitivities of EGFR-tyrosine kinase inhibitors (TKIs) to the mutation. In this case report, we have demonstrated a special mutation, a point mutation at c.2279T>C (p.L760P) in exon 19 of EGFR, which has responded favorably to icotinib in a lung adenocarcinoma patient with brain metastasis. Icotinib is a new type of oral EGFR-TKI developed in China and is the first EGFR-TKI in Asia. Icotinib has the potential to improve the prognosis of lung adenocarcinoma patients and with less toxic-effect.

[Long-term survival of a patient with advanced non-small cell lung cancer on bevacizumab therapy: case report and review of the literature].

We report an advanced stage Chinese female lung adenocarcinoma patient who was negative for epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations, also negative for chinodem microtubule-associated protein-like 4/anaplastic lymphoma kinase (EML4-ALK) gene rearrangement and treated with bevacizumab (15 mg/kg) in combination with 6 cycles of conventional doses of paclitaxel and carboplatin chemotherapy. She was then treated with maintenance bevacizumab for a total of 42 cycles, the total dose of bevacizumab is 44,730 mg. The progression-free survival was 39 months. Our findings suggest that maintenance bevacizumab for the treatment of non-small cell lung cancer (NSCLC) is safe and its benefit for long-term survival overwhelms its side effects.

[Combining bevacizumab with endostatin gets better antitumor efficacy in vivo in lung cancer animal model].

BACKGROUND AND OBJECTIVE: The aim of this study is to investigate difference of antiangiogenesis ablility and interaction about bevacizumab and endostatin in vivo in lung cancer animal model. METHODS: First, we construct a Balb/c mice model with A549 lung adenocarcinoma cell. Then, we divide the mice into four groups randomly. Every group has six mice. CONTROL GROUP: mice injected with normal saline every day aroud the tumor. Endostatin group: mice injected with endostatin (Recombinant endostatin) injection (3 mg/kg) every day Peritumoral. Bevacizumab group: mice injected with bevacizumab twice a week (biw/5 mg/kg) Peritumoral. Combing group: mice were injected with endostatin and bevacizumab (dose just like single drug group). After 16 days, we executed mice and got the tumor tissue for next analysis. RESULTS: Based on this experiment, we found bevacizumab and endostatin expressed the ability for inhibiting tumor growth in vivo. Bevacizumab was more powerful (52.36% vs 38.68%). Combining bevacizumab with endostatin could get better results (64.15%) than single drug did. Bevacizumab played the role by inhibiting VEGF-A expression (60.8%). Endostatin took effect by inhibiting VEGF-A/C (14.6%, 30.3%). Combining group present better antitumor efficacy than any single drug group did. (79.7%, 44.2%). CONCLUSIONS: Both bevacizumab and endostatin present the antiangiogenesis ability in vivo of lung cancer animal model. In our test, bevacizumab show better ability in inhibiting tumor growth than endostatin does. Additional, combing bevacizumab with endostatin reveal better potential to inhibit tumor growth than single drug does.

[Vandetanib treatment in refractory advanced lung adenocarcinoma patients: five cases and review of literature].

BACKGROUND AND OBJECTIVE: Vandetanib is a once-daily oral multi-target inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET) tyrosine kinases. The current study aimed to evaluate the effect and safety of vandetanib administered in refractory advanced lung adenocarcinoma patients. METHODS: Five patients who accepted chemotherapy and Tarceva therapy as first- and second-line treatments received vandetanib (300 mg, oral, once daily). RESULTS: The effects are stable disease on two patients (40%) and progressive disease on three patients (60%). With a median follow-up of 36 months, one patient remained on follow-up. The median progression free survival (PFS) is 2 months, and the mean overall survival is 22.6 months. The adverse events include rash (n=2), skin change (n=2), paronychia (n=2), asymptomatic QTc prolongation (n=2), ST-T change (n=1), diarrhea (n=1), and increased transaminase (n=1). CONCLUSIONS: There were lower incidences of severe side effects with vandetanib therapy in refractory advanced lung adenocarcinoma patients. The results of effect and safety of vandetanib are similar with the related reviewed articles.

[Acceptable safety of bevacizumab therapy in combination with chemotherapy in patients with advanced lung cancer.].

BACKGROUND: Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that selectively binds to and neutralizes the biologic activity of human vascular endothelial growth factor (VEGF). Bevacizumab was approved by the U.S. Food and Drug Administration (FDA) in October 2006 for use in combination with carboplatin and paclitaxel for the initial treatment of patients with unresectable, locally advanced, recurrent, or metastatic, nonsquamous, non-small cell lung cancer (NSCLC). The aim of this study is to observe the safety of bevacizumab therapy in combination with chemotherapy in Chinese patients with NSCLC. METHODS: Patients with advanced non-squamous NSCLC were treated with Bevacizumab 15 mg/kg, d1, repeated every 21 days until PD; Plus paclitaxel 175 mg/m(2), on dl and carboplatin AUC=6 on dl. The cycle was repeated every 21 days. RESULTS: One grade 3 epistaxis was observed in one patient. One grade 4 thrombosis was observed in one patient. 3/4-grade epistaxis and thrombosis was the most significant adverse events. Other adverse effects, such as hemoptysis, hypertension and proteinuria, were not severe and could be well tolerated. CONCLUSIONS: Most chemotherapy-naive patients with advanced non-squamous NSCLC treated with bevacizumab in combination with paclitaxel and carboplatin have little adverse effects that can be well tolerated.

[Clinical Observation of Erlotinib in the Treatment of Advanced and Previously Treated Non-small Cell Lung Cancer.].

BACKGROUND: Erlotinib is a small molecular inhibitor of tyrosine kinase. One study has confirmed that it can prolong the median progression-free survival time (PFS), and can improve the one-year survival rate of patients with advanced non-small cell lung cancer. The aim of this trial is to evaluate the response and adverse reaction of agent erlotinib in advanced and previously treated non-small-cell lung cancer. METHODS: The study was one part of the EAP (Expanded Access Programme) study. Forty-five patients with advanced non-small cell lung cancer, which had been treated with 1-2 regimens containing platinum previously, were treated with erlotinib from Dec 2005. Erlotinib was prescribed at a dose of 150 mg daily. RESULTS: Forty-three patients were evaluated response and all patients were evaluated toxicity. Among these patients, CR 0 case, PR 19 cases (44.2%), RR (CR+PR) 44.2% and SD 13 cases as their best response, disease control rate (DCR=CR+PR+SD) 74.4%, PD 11cases (25.6%). The median progression-free survival time was 4.8 months; the median survival time was 15.0 months; the one-year survival rate was 68.8% (31/45). The median PFS of patients with adenocarcinoma and with non-adenocarcinoma was 7.6 months vs 2.6 months (P=0.018). The drug-related adverse reactions were skin rash (41 cases, 91.1%), billirubine increased (15 cases, 33.3%), ALT increased (9 cases, 20%) and diarrhea (4 cases, 8.9%). For patients with and without skin rash, the median PFS was 7.5 months vs 1.1 months (P=0.001), and the median survival time was 15.6 months vs 5.2 months (P=0.002). CONCLUSIONS: Erlotinib is effective in advanced and previously treated non-small cell lung cancer, and it is much more effective in adenocarcinoma and patients with skin rash. It is well tolerated, only with some minimal adverse reactions.

[A Retrospective Study of Erlotinib in the Treatment of 70 Patients with Non-small Cell Lung Cancer.].

BACKGROUND: Erlotinib is a small molecular inhibitor of tyrosine kinase. Multiple foreign and demestic studies have confirmed that it can prolong the median progression-free survival time (PFS) and the overall survival (OS), which could be more significant in the selected population. In this study we retrospectively oberserved the response, the survival and adverse reaction of erlotinib in non-selected non-small cell lung cancer. METHODS: The retrospective study included seventy non-small-cell lung cancer patients, who were treated with erlotinib from July 2005 to July 2009. Erlotinib was prescribed at a dose of 150 mg daily. RESULTS: Sixty-eight patients were evaluated response. Among these patients, CR 0 case, PR 26 cases, RR (CR+PR) 38.2% and SD 24 cases as their best response, disease control rate (DCR=CR+PR+SD) 73.5%, PD 18 cases (26.5%). Sixty-three patients were evaluated PFS. The median PFS was 3.0 months. The median PFS of adenocarcinoma and non-adenocarcinoma was 3.0 months vs 2.6 months. The drug-related adverse reactions were skin rash, diarrhea and interstitial lung disease (ILD)(4.3%). CONCLUSIONS: Erlotinib is active in non-small cell lung cancer, and it is much more effective in adenocarcinoma and non-smoking patients. There is no difference in response or suvival concerning the sexuality. It is well tolerated in most patients.

[The relationship between EGFR mutations and response and prognosis of tyrosine kinase inhibitors in advanced Non-small-cell Lung Cancer.].

BACKGROUND: It has been proven that epigermal growth factor receptor (EGFR) signal pathway plaied an important role in the oncogenesis and development of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) are currently investigated in the treatment of NSCLC. It was suggested in previous studies that the EGFR gene mutations were correlated with the response to EGFR-TKIs therapy and prognosis of NSCLC. We studied the role of EGFR gene mutations in response to two kinds of TKIs therapy and prognosis of NSCLC in this study. METHODS: The tissue samples of 59 advanced NSCLC patients (34 patients receiving Gefitinib monotherapy and 25 patients receiving Erlotinib monotherapy) were collected, and patient charts were reviewed. The mutations in exons 19 and 21 of EGFR gene were detected by PCR-PAGE and PCR-RFLP respectively. The sequences of interested fragments were verified by direct sequencing. Relationship between EGFR mutation and response to TKIs therapy was analyzed with Chi-Square test. RESULTS: EGFR gene mutations were identified in 22 of 59 samples (37.3%). EGFR gene mutation rate was significantly higher in female, non-smoker and patients with adenocarcinoma than in others (50% vs 18.9%, P <0.05). The patients with EGFR gene mutation had a better response to TKIs therapy than those without (86.4% vs 54.1%,P <0.05). The patients with EGFR gene mutation had slower disease progression and longer overall survival than those without, but statistically non-significant (P >0.05). CONCLUSIONS: EGFR gene mutation occurs more frequently in female, non-smoker and patients with adenocarcinoma. In patients with advanced NSCLC, EGFR mutation is associated with good response to EGFR-TKIs therapy.

[A randomized clinical trial of Uroacitides combined with NP and NP regimen alone for advanced non-small cell lung cancer].

BACKGROUND: Uroacitides is a group of cell differentiation inducers, which is purified from fresh human urine. Preclinical studies of Uroacitides have showed that cancer cells could be induced to differentiate, and the growth of cancer cells could be inhibited by Uroacitides. The aim of this study is to compare the efficacy and toxicity between Uroacitides combined with NP regimen and NP alone in treatment of advanced non-small cell lung cancer (NSCLC). METHODS: Forty-two cases of advanced NSCLC were randomized into Uroacitides+NP and NP groups. NP group: NVB 25mg/m² on days 1 and 8, DDP 75mg/m² on day 1. Uroacitides combined with NP group: Uroacitides of 300mL was given through subclavian catheter daily for 7 days prior to the NP chemotherapy, then concurrently with NP regimen for 2 cycles, except the days of administration of chemotherapy. RESULTS: In the Uroacitides+NP group, the overall response rate was 44.4%, and 20.0% in the NP group (P > 0.05). The median survival time was 9 months in the Uroacitides+NP group and 6 months in the NP group (P=0.0287). The main toxicities were myelosuppression, gastrointestinal reaction and alopecia, and there was no significant difference in incidences of toxicities between the two groups (P > 0.05). CONCLUSIONS: Uroacitides combined with NP regimen shows a good curative effect and low toxicity, and may significantly prolong the median survival time for advanced NSCLC.

[Phase II clinical trial of homemade human rh-endostatin in the treatment of patients with stage IIIB-IV non-small cell lung cancer].

BACKGROUND: To evaluate the efficacy and safety of homemade human rh-endostatin (YH-16) combined with NP regimen (vinorelbine+cisplatin) for stage IIIB-IV non small cell lung cancer (NSCLC), and to compare with NP regimen alone. METHODS: Eighteen NSCLC patients were divided into two groups. Group A ( n =9) received YH-16 combined with NP plan. Group B ( n =9) received NP regimen. They were treated with 2 or 3 cycles of chemotherapy. The overall response, time to progression (TTP), quality of life (QOL) and safety were observed. RESULTS: The overall response was 22.2% in group A, and 0% in group B ( P > 0.05). The clinical benefit rate was 100% in group A, and 44.4% in group B ( P < 0.05). There was no significant relationship between response and clinical pathological characteristics of patients ( P > 0.05). The TTP was 178.8±70.8 days in group A and 85.4±48.2 days in group B ( P < 0.05). The main toxicities of the two groups were hematological toxicities, nausea and vomiting. No significant difference in incidence of toxicity was observed between the two groups ( P > 0.05). CONCLUSIONS: The rh-endostatin combined with NP regimen for NSCLC tends to show a better chemotherapeutic effect and less toxicity than NP regimen alone. It is worthy of extensive clinical trial.

[Paclitaxel combined with platinum-based chemotherapy as second-line treatment in patients with advanced non-small cell lung cancer: A forty case-report].

BACKGROUND: To evaluate the activity and toxicity of paclitaxel as second-line treatment for advanced non-small cell lung cancer (NSCLC). METHODS: Forty patients with recurrent advanced NSCLC were enrolled. Thirty-six patients were managed with regular regimen. Paclitaxel 135 mg/m², 3 h, on day 1; DDP 75 mg/m² or carboplatin 300-350 mg/m² on day 2. Four patients were managed with weekly regimen. Paclitaxel 60 mg/m²,3 h, on days 1,8,15; DDP 75 mg/m² on day 2. It was repeated every three or four weeks, up to two to four cycles. RESULTS: Thirty-six cases were evaluated for response and 27 for survival. The objective response rate was 13.9% (5/36). At least one tumor-related symptom relief was observed in 21 patients (58.3%). The median survival duration was 26.4 weeks and 1-year survival rate was 8% (4/36). The main toxicities included myelosuppression, fatigue and myalgia-arthralgia neuropathy. CONCLUSIONS: Paclitaxel has advantage to be well-tolerated and improve tumor-related symptom. Further studies with standardization of dose and regimen will be needed to clarify its role in the second-line treatment.

[Clinical research on combined chemotherapy of vinorelbine and cisplatin in the treatment of non-small cell lung cancer].

BACKGROUND: To evaluate the efficacy, side-effects, median survival duration and survival rate of vinorelbine (NVB) combined with cisplatin (DDP) in the treatment of non-small cell lung cancer (NSCLC). METHODS: A total of 220 patients with inoperable NSCLC received NVB and DDP combined chemotherapy: NVB 25-30 mg/(m²*d) on days 1 and 5 (or 8), DDP 60-80 mg/(m²*d) on day 2. The schedule was repeated every 28 days. The efficacy and side-effects were analysed and followed-up after at least two cycles of chemotherapy. RESULTS: The overall response rate (CR+PR) was 30.9% (68/220). The response rate was 31.3% (51/163) in initial treatment group, and 29.8% (17/57) in retreatment group. The median survival duration was 8.3 months. The 1-, 2- and 3-year survival rates were 39.23%, 19.31% and 6.32%, respectively. The main side-effects were myelosuppression and digestive tract reactions. CONCLUSIONS: Vinorelbine plus cisplatin is an effective and well-tolerated regimen for non small cell lung cancer and myelosuppression is its dose-limiting toxicity.

[Serratia marcescens vaccine in the treatment of malignant pleural effusion].

OBJECTIVE: To evaluate the efficacy and toxicity of Serratia marcescens (S311) vaccine in the treatment of malignant pleural effusion. METHODS: Thirty-four patients with malignant pleural effusion were given S311 as intrapleural injection with a dose of 10(9) U (0.32 mg) on D 1, 8 and 15, and observed for four weeks. RESULTS: The overall response rate (CR + PR) was 97.1% (CR in 12 patients and PR in 21 patients). The systemic toxicity was mild, including fever (82.4%), pleuritic pain (50.7%), nansea (26.5%), dyspnea (17.5%) and chills (5.9%). CONCLUSION: Serratia marcescens vaccine is effective for malignant pleural effusion, with tolerable toxic effects. Further study is warranted.