Yunzhong Zhu

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.

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.

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.

Target therapy of gefitinib in advanced adenocarcinoma of the lung

BACKGROUND Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which is used to treat advanced non-small cell lung cancer, especially adenocarcinoma. The aim of this study is to evaluate the efficacy, side effects and prognostic factors of gefitinib in adenocarcinoma of the lung. METHODS A total of 26 patients with advanced adenocarcinoma of the lung were enrolled in the study. Gefitinib was orally administered 250mg once daily until disease progression or the occurrence of intolerable toxicity. They were evaluated regularly and their survival was analyzed. RESULTS In 26 patients, there was 1 with complete regression (3.8%), 11 with partial response (42.3%), 9 with stable disease (34.6%) and 5 with progression of disease (19.2%). The objective response rate was 46.2% and the disease control rate was 80.8%. The median progression-free survival time was 8.2 months and the median overall survival time was 10.4 months. The 1-year survival rate was 31.6%. Age ( < 70 years old), skin rash and CEA decrease were significantly related to longer survival, however, times of prior chemotherapy and gefitinib treatment stage did not influence the survival. Mean PS (ECOG) was 3.0 before treatment, and 1.8 after treatment. Mean symptom relief time was 5.2 days. CONCLUSIONS Gefitinib is an effective target drug with slight side effect. It can significantly improve quality of life of patients with adenocarcinoma. It can be used as first-line therapy to patients who are not suitable for chemotherapy.

[Adverse events of afatinib as first-line treatment for five cases of advanced lung adenocarcinoma and review of literature].

BACKGROUND AND OBJECTIVE Afatinib is an irreversible ErbB-family blocker with a clinical activity in non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. The aim of this study is to assess the safety of afatinib in patients with advanced lung adenocarcinoma. METHODS Patients with lung adenocarcinoma (stage IIIb or IV) with EGFR mutations were first-line treated with an oral administration of afatinib (40 mg/d) until disease progression. Adverse events, effects, and survival condition were observed. RESULTS The most common adverse events were diarrhea (n=5, 100%), skin rash (n=4, 80%), and mucositis/stomatitis (n=4, 80%). Moderate toxicities not exceeding grade 3 were observed. Relatively, the most serious adverse reaction was mucositis/stomatitis. Mild diarrhea occurred in all patients. Three patients experienced temporary drug withdrawal and dose reduction because of adverse reaction. Among the four patients who were evaluated, partial response was observed in two patients (50%), one with stable disease (25%) and one with progressive disease (25%). Median progression-free survival was 9.7 months, whereas median overall survival was 18.4 months. CONCLUSIONS Afatinib was approved as first-line treatment for patients with advanced lung adenocarcinoma. The most common adverse events were diarrhea and skin rash. However, mucositis/stomatitis related to afatinib should also be considered. Considering the small number of cases, the conclusion requires more trials for confirmation.

[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.

Comparison of Oral Topotecan/Intravenous Cisplatin (TC) with Intravenous Etoposide/ Cisplatin (EP) as First Line Chemotherapy in Untreated Small Cell Lung Cancer Patient

BACKGROUND Topotecon is a specific inhibitor of topoisomerase I. It is an effective drug of small cell lung cancer. An oral formulation of topotecan is available and has just rectified to treat extensivedisease small cell lung cancer by FDA this year. The aim of this trial is to compare oral topotecan/intravenous cisplatin (TC) with intravenous etoposide/cisplatin (EP) in patients untreated small cell lung cancer. METHODS Sixty-six patients were enrolled. Thirty patients were assigned to oral topotecan 1.4 mg*m(-2)*d(-1), from d1 to d5, with cisplatin 75 mg/m(2) on d1. Thirty-six patients were assigned to etoposide 100 mg*m(-2)*d(-1), from d1 to d3, with cisplatin 75 mg/m(2) on d1 every 21 days. RESULTS Response rate was similar between groups TC, 53.3% vs EP, 60.0%. Overall survival was little different TC, 14.58 month vs EP, 12.19 months. The regimens were similarly tolerable. Grade 3/4 neutropenia and thrombocytopenia occurred more frequently with EP (42.8% vs 10.0% and 11.4% vs 3.3%, respectively), whereas grade 3/4 anaemia occurred more frequently with TC (10% vs 2.8%). CONCLUSIONS Oral topotecan/cisplatin provide similar efficacy and tolerability to the standard etoposide/cisplatin in patient untreated small cell lung cancer. It may provide more convenience method to intravenous treatment.

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 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.

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.