• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4635-4639
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• 2013

Multi-drug resistance (MDR) is an essential aspect of human lung cancer chemotherapy failure. Recent studies have shown that vinorelbine is involved in underlying processes in human tumors, reversing the MDR inseveral types of cancer cells. However, the roles and potential mechanism are not fully clear. In this study, we explored effects of vinorelbine in multi-drug resistance reversal of human lung cancer A549/DDP cells. We found that vinorelbine increased drug sensitivity to cisplatin and intracellular accumulation of rhodamine-123, while decreasing expression of P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP1) and glutathione-S-transferase ${\pi}$ (GST-${\pi}$) in A549/DDP cells. At the same time, we also established downregulation of p-Akt and decreased transcriptional activation of NF-${\kappa}B$ and twist after vinorelbine treatment. The results indicated that vinorelbine might be used as a potential therapeutic strategy in human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4159-4163
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• 2014

Background: The aim of this study was to evaluate the efficacy of alternating etoposide-cisplatin and vinorelbine-cisplatin (EP-NP) compared with an etoposide-cisplatin (EP) regimen for advanced combined small cell carcinomas. Materials and Methods: Histologically confirmed combined small cell carcinoma patients who met the inclusion criteria were randomly assigned (1:1) into either the EP-NP setting (group A) or the EP setting (group B). The primary endpoint was progression-free survival in patients who received at least one dose of treatment. Results: Eighty-two patients entered into this trial, 42 in group A and 40 in group B. The objective response rates in group A and group B were 42.9% and 32.5%, respectively (p=0.334). Survival analysis showed that median progression-free survival was 6.1 months in group A, which was significantly longer than the 4.1 months in group B (p=0.041). However, as to overall survival, no significant difference was found between the two groups (11.0 vs 10.1 months in groups A and B, respectively, p=0.545). No unexpected side effects were observed in either group. Conclusions: The EP-NP regimen for combined small cell carcinomas prolonged progressio-nfree survival compared with the EP regimen. Further clinical investigations are warranted.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4505-4510
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• 2012

Purpose: To determine the efficacy of post-operative chemotherapy with cisplatin plus vinorelbine (NP) in Chinese patients with non-small cell lung cancer (NSCLC). Methods: A total of 451 patients with NSCLCs at stages I, II, and IIIA after surgical resection were treated with cisplatin plus vinorelbine for 4 cycles or volunteers observed between January 2002 and November 2004 and were followed for five years. The therapeutic efficacy was evaluated with reference to overall survival (OS) and disease-free survival (DFS), and adverse effects were also recorded. Potential factors affecting the lengths of OS and DFS were analyzed by multivariate analysis. Results: Most patients (86.7%) completed at least 4 cycles of treatment. Patients with chemotherapy survived significantly longer than those in the observation group (p<0.001). The absolute improvements in the 2 and 5-year OS were 3.8% [hazard ratio (HR) =0.674, 95% confidence interval (CI): 0.554-0.820, P<0.0001] and 13.0% (HR=0.732, 95% CI: 0.579-0.926, P=0.009), respectively. The improvement at 4-year DFS was 2.1% (HR=0.327, 95% CI: 0.214-0.500, P<0.0001). Stratification analysis revealed that older age, histological type, pathological degree, but not the gender and smoking status, are independent factors affecting the length of survival in this population. Many patients (63.3%) had grade 1-III tolerable adverse effects, and there was no treatment-related death. Conclusions: Post-operative chemotherapy with NP regimen is effective and tolerable in Chinese patients with NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4703-4706
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• 2012

Objective: To compare efficacy and safety profile of vinorelbine, ifosfamide and cisplatin (NIP) with etoposide and cisplatin (EP) in the treatment of advanced combined small cell lung cancer (c-SCLC). Methods: From January 2006 to December 2010, 176 patients with advanced c-SCLC were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were progression free survival (PFS), response rate (RR) and toxicity. Results: Overall RR was 30.0% in the NIP and 38.5% in the EP group; there was no significant difference (P=0.236). The PFS in the EP group was little longer than that of NIP group, with 6.5 months for EP and 6.0 months for NIP group, but the difference was statistically non-significant (P=0.163). The median OS and one year survival rates were 10.4 months and 36.3% for NIP group, and 10.8 months and 49.0% for EP respectively, EP showing a survival benefit, although this was not statistically significant. Both groups well tolerated the adverse effects. The incidence of grade I-II leucopenia and alopecia in the NIP group was significantly higher than that of EP group (32.5% vs. 10.4% (P<0.001, 35.0% vs. 12.5%, P<0.001). Conclusion: the ORR, PFS and OS in NIP were slightly inferior to traditional regimen EP. The toxicity of NIP can be considered tolerable. The usage of three drugs combination in the treatment of mixed SCLC remains uncertain. Nevertheless, the results need to be further confirmed by large, prospective clinical trials.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4481-4485
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• 2012

Background: Chemotherapy induced leutropenia has been shown to be associated with improved treatment outcomes in selected solid tumors. We studied the association of chemotherapy induced leutropenia with treatment related outcomes in advanced non-small-cell lung cancer. Methods: This is a prospective analysis of patients receiving chemotherapy for advanced NSCLC at the Shandong Cancer Hospital from 2005-07.The chemotherapy included cisplatin $35mg/m^2$, IV on $d_{1,2}$ and vinorelbine $25mg/m^2$ IV on $d_{1,8}$ every 21 days. Patients were stratified into three groups (A) those experiencing grades 0 leucopenia, group (B) grades 1-2 and group (C) grades 3-4. The outcomes studied were response rate (RR), disease control rate (DCR), and time to progression (TTP). Results: 128 patients were studied. The RRs in groups A, B and C were 30.8%, 56.8% and 71.4%, respectively, p=0.010. The DCRs were 61.5%, 83.8% and 92.9%, respectively, p=0.009 and the median TTPs were 150 days (95%CI: 91-209), 189 days (95%CI: 181-197) and 207 days (95%CI: 172-242), p=0.009. The differences in RR and TTP were significant. In patients whose CIL kept on 10 days at least, the TTP was significantly prolonged, p=0.0213, and the same was the case for those experiencing grades 1-2 leucopenia and ECOG 0, p=0.0412. Conclusions: Occurrence of CIL correlated with RR and TTP in patients with advanced NSCLC receiving cisplatin and vinorelbine chemotherapy, especially in patients experiencing grades 1-2 leucopenia and ECOG 0, and the same for those with CIL persisting for 10 days at least. CIL could be a biological measure of drug activity and a marker of efficacy.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1863-1867
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• 2012

Background: Maintenance chemotherapy is one strategy pursued in recent years with intent to break through the chemotherapy plateau for advanced non-small cell lung cancer (NSCLC). However, given the toxicity, platinum-based combinations are rarely given for this purpose. We carried out the present prospective study of triplet platinum-based combination sequential chemotherapy in advanced NSCLC to investigate if patients could tolerate and benefit from such intensive treatment. Methods: From Dec 2003 to Dec 2007, 190 stage IIIB and IV NSCLC patients in Sun yat-sen University sequentially received the 3 platinum-based combination (TP-NP-GP) treatment (T: paclitaxol175$mg/m^2$ d1; N: vinorelbine25$mg/m^2$ d1 and 8; G: gemcitabine1$g/m^2$ d1 and 8; P: cisplatin20$mg/m^2$ d1-5; repeated every 3 weeks). Patients were followed up to at least 3 years to obtain survival data. Treatment toxicities and the quality of life (QOL) were assessed during the whole treatment. Results: There were 187 patients evaluable. The TP, NP and GP response rates with sequential use were 42.8% (80/187), 41.1% (65/158) and 28.8% (21/73) respectively. Median survival time was 18.2 months and the 1, 2 and 3 year overall survival (OS) rates were 78.7%, 38.5% and 21.3%. Patients receiving > 6 cycles of chemotherapy had significantly longer OS and TTP (MST 25.3 vs. 14.5 months, TTP 15.1 vs. 9.1 months). The QOL on the whole for the patients was improved after chemotherapy. Conclusions: The sequential chemotherapy strategy with triplet platinum-based combination regimens can improve the survival outcome and the quality of life of advanced non-small cell lung cancer patients.

• Tuberculosis and Respiratory Diseases
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• 제57권6호
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• pp.557-566
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• 2004

연구배경 : 비소세포폐암 중 IIIA병기는 같은 병기라도 다양한 임상적 경과를 밟고 어느 한가지 치료만으로는 치료 성적이 좋지 못하다. 이에 최근에는 다각적치료(항암, 화학치료, 방사선치료 및 수술적 치료)가 치료의 근간이 되고 있고 이에 대한 연구가 많이 시도되고 있으며 일부에서는 긍정적인 결과를 보고 하고 있다. 이에 저자들은 유도화학요법에 근간을 둔 다각적 치료의 효과를 살펴보고자 연구를 계획하였다. 방 법 : 1997.1월부터 2002.12월까지 충남대학교 병원에 내원하여 임상적으로 비소세포폐암 IIIA병기 진단을 받고 초치료로 유도화학치료를 시행받은 환자에 대하여 다각적 치료의 반응률, 재발율 및 생존기간등을 살펴보았다. 결 과 : 1) 유도화학요법은 74명에게서 시행되었고 반응률은 44.6%(완전관해 1.4% 및 부분반응 3.2%)였고, 고전적약(VPP)과 신약과의 반응률은 차이가 없었다(38.9%vs. 50%, p=0.506). 임파선의 반응률은 다발성 N2이상 병기로 수술적 치료에 어려움이 있다고 판단됐던 37명중 18명(54%)에서 단발성 N2이하로 병기하향을 보였고 이중 수술거부 6명과 폐기능문제 4명을 제외한 8명(21%)이 수술을 시행 받았다. 단발성 N2병기의 경우는 37명중 33명(89%)에게서 단발성 N2이하로 병기유지 내지 하향을 보였고 수술거부 7명과 폐기능문제 5명을 제외한 21명(56.7%)이 수술을 시행 받았다. 유도화학요법 후 다발성 N2였으나 수술적 절제가 가능하다고 판단됐던 4명의 경우에도 수술이 시행되어 전체 환자 중 수술적 치료는 33명(44.5%)에게서 시행되었으며, 완전절제는 30명(40.5%)이었고, 2명(2.6%)의 경우는 불완전 절제, 그리고 1명(1.3%)의 경우는 산소 포화도가 유지가 되지 않아 바로 봉합하였다. 2) 유도화학요법후 WHO기준 3이상의 호중구 감소증은 20명(25.7%)에서 발생하였고 이에 병발된 폐렴은 3명에게서 발생하였으나 이로 인한 사망은 없었다. 3) 수술적 절제가 불가능하여 방사선 치료를 시행하였던 27명의 반응률은 완전관해가 4.8%였고 부분반응은 11.9%였다. 4) 완전 절제되었던 군의 무병지속기간은 13.6개월이었고, 2년의 추적관찰기간 시점의 재발률은 52%였으며, 추가 방사선 치료군의 국소 재발율은 의미있게 적었다(0% vs. 40%, 0.02). 완전 절제되지 못하였거나 불완전 절제된 군의 무진행 질병기간은 11.2개월이었고, 2년의 추적관찰기간 시점의 병의 진행률은 66.7%였다. 5) 전체 대상환자의 중앙생존기간은 25.1개월이었고, 유도화학요법 후 수술 적으로 완전절제를 이루었던 군이 국소 치료로 방사선 치료를 시행하였던 군에 비하여 생존기간이 유의하게 길었지만(31.7개월 vs. 26.1개월, p=0.04), 완전절제 된 군의 추가 방사선 치료에 따른 생존 이득은 없었다. (34.9개월 vs. 32.2개월, p=0.48) 결 론 : 이상의 결과로 임상적 IIIA병기 비소세포폐암의 치료로 다각적 치료시 유도화학요법 후 가능하다며 수술적으로 완전절제를 이루는 것이 가장 좋은 치료라 생각된다. 하지만 전체적인 생존율은 그다지 높지 못하여 유도화학요법시 추가적인 방사선 치료, 수술 후 보조적 항암화학요법, 그리고 생물학적 치료제 등에 대한 보다 많은 3상 연구가 필요하리라 생각된다.