Induction Docetaxel and Cisplatin Followed by Weekly Docetaxel and Cisplatin with Concurrent Radiotherapy in Locally Advanced Stage III Non Small Cell Lung Cancer (LA-NSCLC)-A Phase II Study

Purpose: The objective of this phase II study was to document the activity and to evaluate the toxicity of docetaxel and cisplatin as induction chemotherapy followed by concurrent docetaxel and cisplatin with thoracic radiation in locally advanced stage III non small cell lung cancer. Patients and Methods: Twenty-seven patients with stage III locally advanced non-small cell lung cancer received induction chemotherapy with two cycles of docetaxel 75mg/m2 and cisplatin 75mg/m2 D1 every 3 weeks. Patients without disease progress after induction chemotherapy were assigned to concurrent chemoradiotherapy 20mg/m2 docetaxel&25mg/m2 cisplatin administrated on day 1 every week for 6 weeks along with concurrent radiotherapy at a dose of 60Gy in 30 fractions (2 Gy/fraction and 5 fractions per week). The primary endpoint was to determine the overall response rate (ORR), the secondary endpoint was to evaluate time to progression (TTP) and safety profile. Results: After induction chemotherapy, the overall response rate (ORR) was 44.4%, 23 patients without disease progress were assigned to concurrent treatment with an overall response rate of 65%. Median survival time was 17 months, time to progression was 11.5 months and the one-year survival was 58%. Neutropenia was the most common toxicity during induction therapy (26% expressed grade 3-4) whereas esophagitis was the most common toxicity during concurrent phase (17.3% expressed grade 3-4); toxicities were manageable. Conclusion: Induction chemotherapy by docetaxel and cisplatin followed by weekly docetaxel and cisplatin with concurrent thoracic radiation therapy is feasible and tolerable. These results warrant further large randomized studies to document and confirm the effectiveness of this regimen. Key Words: Lung cancer , Docetaxel , Cisplatin , Concurrent chemoradiotherapy.     

多西他赛和顺铂同步放化疗治疗局部晚期鼻咽癌临床观察

目的观察局部晚期鼻咽癌同步放化疗的疗效及毒副反应。方法 70例局部晚期鼻咽癌,采用静脉化疗2周期,化疗方案：多西他赛75 mg/m2,分于第1,8天给药;顺铂（DDP）25 mg/（m2.d）d1-3天,21天为1周期。同时给予同步放疗,鼻咽部原发灶给予6 MV-X线和15 MV-X线DT 70 Gy～78 Gy/7-8周。结果 70例中CR 20例,PR 37例,总有效率81.4%。1年、3年生存率分别为98.4%、83.9%。主要毒副反应为骨髓抑制、急性口腔黏膜炎、恶心呕吐、皮肤反应。结论多西他赛和顺铂同步放化疗治疗局部晚期鼻咽癌疗效较好,毒副反应可以耐受。     

Ⅲ期非小细胞肺癌多学科综合治疗的临床效果

目的：比较同时放化疗加巩固化疗（CCT）和同时放化疗（CRT）对Ⅲ期非小细胞肺癌的近远期疗效及不良反应.方法：57例Ⅲ期非小细胞肺癌分为2组,CRT组（28例）采用多西他赛和顺铂每周化疗同时放疗,放疗采用三维适形放疗,化疗采用多西他赛30mg/m2和顺铂20mg/m2,每周重复,共5周,CCT组（29例）先按CRT组方案治疗结束后再加用多西他赛75mg/m2和顺铂75mg/m2巩固化疗,每3周重复,共2周期.结果：CCT组和CRT组有效率分别为68.9%和53.6%,1、2、3年生存率及中位生存期CCT组分别为64.5%、36.2%、17.3%和18个月,CRT组为48.6%、21.2%、10.7%和13个月,有统计学差异.两组不良反应CCT组血液学毒性较CRT组明显.结论：Ⅲ期非小细胞肺癌患者同期放化疗后巩固性化疗可提高近期疗效、中位生存期,含紫杉类与顺铂的化疗方案可认为是最佳的选择,但其不良反应也明显增加,作为标准治疗仍需临床试验证实.     

Docetaxel and concurrent radiotherapy after two cycles of induction chemotherapy with cisplatin and vinorelbine in patients with locally advanced non-small-cell lung cancer. A phase II trial conducted by the Groupe Francais de Pneumo-Cancerologie (GFPC)

CONTEXT: The most satisfactory treatment for patients with locally advanced non-small-cell lung cancer (NSCLC) is combination chemotherapy-radiotherapy (CT-RT). The optimal treatment modalities remain to be determined. OBJECTIVE: We conducted a multicenter phase II trial of the docetaxel-radiotherapy combination after induction chemotherapy with cisplatin-vinorelbine. The main endpoint was the objective response rate. PATIENTS AND METHODS: Patient with inoperable stage locally advanced NSCLC received induction chemotherapy consisting of two cycles of cisplatin 100 mg/m2 on D1 and vinorelbine 25 mg/m2 on D1, D8, D15 and D22. Patients with responses or stable disease then received concurrent RT-CT consisting of 25 mg/m2/week docetaxel and single-fraction radiotherapy (66 grays (Gy) in 33 fractions) over 6.5 weeks. RESULTS: Fifty-six patients were enrolled from 1 July 2000 to 31 December 2001. Sixteen patients left the trial after induction chemotherapy, eight for progression, five for toxicity, and two for intercurrent events. One patient underwent surgery after induction chemotherapy. In total, 40 of the 56 patients received RT-CT. Twelve (30%) of these 40 patients experienced grade III or IV pulmonary or esophageal toxicity. In the intention-to-treat analysis, the objective response rate was 46.4% (95% CI 33.0-60.2). The median time to progression was 6.2 months [1.1-26.0]. The median survival time was 13 months [0.3-44.9 months]. Nine patients progressed during RT-CT, six with brain metastases. CONCLUSION: Weekly docetaxel with concurrent radiotherapy, following chemotherapy is acceptable. The tumor response rate is moderate. Further trials are required to determine the risk-benefit relationship of this treatment schedule, and the possible benefit of adding other cytotoxic drugs.     

多西他赛加顺铂诱导化疗联合同期放化疗局部晚期非小细胞肺癌的临床观察

目的 评价TP方案诱导化疗联合同期放化疗局部晚期非小细胞肺癌的近期疗效和不良反应。方法 病理证实的局部晚期非小细胞肺癌86例,随机分成同期放化疗联合TP方案诱导化疗(ICCRT) 组和单纯同期放化疗(CCRT) 组。放疗均采用调强放疗。治疗结束后比较两组疗效、生存率和不良反应。结果 86例患者的随访率为100%。ICCRT组和CCRT组的有效率分别为80%和70%(χ²=1.26,P=0.261),1、2、3年总生存率分别为85%和65%、50%和40%、44%和33%(χ²=3.90,P=0.048),主要不良反应白细胞减少(43例和32例,χ²=3.48,P=0.062)、放射性食管炎(26例和20例,χ²=0.12,P=0.730)、血红蛋白减低(26例和16例,χ²=2.34,P=0.126)和放射性肺炎(13例和9例,χ²=0.37,P=0.541)。结论 ICCRT能明显提高局部晚期非小细胞肺癌的总生存率,且与CCRT相比并不增加局部不良反应。     

Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer

Recent studies have suggested the superiority of concomitant over sequential administration of chemotherapy and radiotherapy. Docetaxel and cisplatin have demonstrated efficacy in advanced non-small-cell lung cancer (NSCLC). This study evaluated the safety, toxicity, and antitumour activity of docetaxel/cisplatin with concurrent thoracic radiotherapy for patients with locally advanced NSCLC. Patients with locally advanced NSCLC (stage IIIA or IIIB), good performance status, age or=3 toxicities of 71, 60, 24, and 19%, respectively. Toxicity was significant, but manageable according to the dose and schedule modifications. Dose intensities of docetaxel and cisplatin were 86 and 87%, respectively. Radiotherapy was completed without a delay in 67% of 42 patients. The overall response rate was 79% (95% confidence interval (CI), 66-91%). The median survival time was 23.4+ months with an overall survival rate of 76% at 1 year and 54% at 2 years. In conclusion, chemotherapy with cisplatin plus docetaxel given on days 1, 8, 29, and 36 and concurrent thoracic radiotherapy is efficacious and tolerated in patients with locally advanced NSCLC and should be evaluated in a phase III study.     

三维适形放疗同步奥沙利铂化疗治疗不可手术Ⅲ期非小细胞肺癌的临床研究*

目的　探讨三维适形放疗同步每周小剂量奥沙利铂化疗治疗不可手术Ⅲ期非小细胞肺癌（ＮＳＣＬＣ）的疗效、毒副反应以及生存期。方法　将６４例不可手术的Ⅲ期ＮＳＣＬＣ患者分为诱导化疗后胸部三维适形放疗（３Ｄ ＣＲＴ）同步小剂量奥沙利铂化疗组（同步组）３２例和诱导化疗后胸部三维适形放疗组（序贯组）３２例。两组均采用以铂类为基础的化疗方案先诱导化疗２周期,获疾病控制者（ＣＲ＋ＰＲ＋ＳＤ）休息３～４周开始胸部三维适形放疗,同步组在放疗的同期给予小剂量奥沙利铂（５０ｍｇ／次）化疗,每周１次,直至放疗结束。两组胸部放疗总剂量相同均为６６Ｇｙ／３３ｆ,每周一至周五。两组放疗结束后获疾病控制者休息４～６周后进一步行多西他赛或吉西他滨单药巩固化疗２周期。结果　中位随访１３.５个月,同步组和序贯组的中位总生存期（ＯＳ）分别为１７.０个月和１４.５个月,中位无进展生存期（ＰＦＳ）分别为１２.９个月和９.２个月,１年和２年生存率分别为６２.５％、５６.３％和２８.１％、２１.９％,１年和２年无进展生存率分别为４０.６％、３１.３％和１５.６％、１２.５％。毒副反应同步组的２～３级放射性食管炎发生率高（Ｐ＜０.０５）,其他治疗相关毒性两组比较无统计学差异（Ｐ＞０.０５）。结论　诱导化疗后胸部３Ｄ-ＣＲＴ同步每周小剂量奥沙利铂化疗治疗不可手术Ⅲ期ＮＳＣＬＣ安全有效,毒性反应轻,患者耐受性好。     

TP方案诱导化疗序贯同期放化疗治疗局部晚期鼻咽癌的临床观察

目的 比较多西他赛+顺铂（TP方案）或顺铂+氟尿嘧啶（PF方案）诱导化疗3周期后联合同步放化疗治疗局部晚期鼻咽癌的疗效和安全性。方法 将局部晚期鼻咽癌患者随机分为两组：A组30例接受TP方案诱导化疗（多西他赛75 mg／m2 d1+顺铂75 mg／m2 d2）,每3周重复;B组29例接受PF方案诱导化疗（顺铂75 mg／m2 d1+氟尿嘧啶750 mg／m2 civ d1～d5）。诱导化疗结束3周后行三维适形放疗,20 Gy／次,5次／周,共6周,DT 60 Gy,并联合同步化疗（顺铂80 mg／m2,d1,每3周重复）。评价两组患者的疗效及毒副反应,并随访生存情况。结果A、B两组的有效率（RR）分别为76.7％、79.3％（P.0.05）;中位生存时间分别为39.4个月、36.0个月（P＞0.05）。A、B两组中位无进展生存时间分别为12.7个月、10.3个月,差异有统计学意义（P=0.044）。两组毒副反应主要为血液学毒性、黏膜炎等,差异无统计学意义（P＞0.05）。结论 TP方案诱导化疗联合同期放化疗可延长患者的中位无进展生存时间,且未增加不良反应,可作为局部晚期鼻咽癌治疗方案之一。     

Phase II study of bi-weekly docetaxel and carboplatin with concurrent thoracic radiation therapy followed by consolidation chemotherapy with docetaxel plus carboplatin for stage III unresectable non-small cell lung cancer

OBJECTIVE: Docetaxel and carboplatin (DC) have demonstrated activity as radiation sensitizers in pre-clinical studies. The aim of this phase II study was to evaluate the efficacy and toxicity of DC with concurrent thoracic radiation therapy (TRT) followed by consolidation chemotherapy with DC for stage III unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-three previously untreated patients with inoperable, locally advanced (LA) NSCLC received docetaxel 30 mg/m2 over 1 h and carboplatin at an AUC of 3 every 2 weeks for six courses--four courses during concurrent chemoradiotherapy and two courses following completion of radiotherapy. Concurrent TRT was performed in 2-Gy daily fractions to a total dose of 60 Gy. RESULTS: Among 32 evaluable patients, the overall response rate was 91%, with two complete responses (CR) and 27 partial responses (PR). Median survival time by intention-to-treat analysis was 27 months, with survival rates of 76% at 1 year and 61% at 2 years. Serious side effects were generally limited to grade 3 neutropenia in 6%, grades 3 and 4 pulmonary toxicity in 6 and 3%, respectively, and grade 3 esophagitis in 3% of patients. CONCLUSIONS: DC with concurrent TRT followed by consolidation chemotherapy was highly active with manageable toxicity in patients with stage III unresectable NSCLC.     

Phase II study of induction chemotherapy with gemcitabine and vinorelbine followed by concurrent chemoradiotherapy with oral etoposide and cisplatin in patients with inoperable stage III non-small-cell lung cancer

PURPOSE: For locoregionally advanced inoperable non-small-cell lung cancer (NSCLC), concurrent chemoradiotherapy has become a standard therapy. We conducted a Phase II trial to examine the efficacy and toxicity of adding gemcitabine and vinorelbine induction chemotherapy to concurrent chemoradiotherapy with oral etoposide and cisplatin. METHODS AND MATERIALS: Eligibility included inoperable clinical Stage III NSCLC without pleural effusion, ECOG performance status 0-1, and weight loss < or =5%. Induction chemotherapy consisted of three cycles of gemcitabine 1,000 mg/m2 and vinorelbine 30 mg/m2, each given i.v. on Days 1 and 8, every 3 weeks. During once-daily thoracic radiotherapy (1.8 Gy/day, total 63 Gy), two cycles of oral etoposide (100 mg on Days 1-5 and 8-12) plus cisplatin (50 mg/m2 on Days 1 and 8) were given concurrently 4 weeks apart. RESULTS: Between April 2002 and November 2003, 42 patients were enrolled and 40 were included in response and toxicity evaluation. The median age was 59 years and 13 patients had IIIA and 27 had IIIB; 24 had squamous ca, 12 had adenocarcinoma, and 4 had others. Objective tumor responses were obtained in 29 patients (72.5%), including 18 (45.0%) after induction chemotherapy. After a median follow-up of 23.8 months, the median survival time and progression-free survival was 23.2 months and 10.9 months, respectively, with 2-year survival rate of 43.9%. For the patients with supraclavicular nodal involvement, the median survival time was 11.8 months with 2-year survival rate of 16.7%, whereas the corresponding figures were 27.8 months and 52.0%, respectively, for those without supraclavicular nodal involvement. Toxicity of induction chemotherapy was mild and well tolerated. However, concurrent chemoradiotherapy was associated with G3/4 hematologic toxicity in 75.7%, G3 esophagitis in 24.2%, and two treatment-related deaths. There were nonlife-threatening late toxicities in additional 6 patients. CONCLUSIONS: Induction chemotherapy with gemcitabine and vinorelbine followed by concurrent chemoradiotherapy with etoposide and cisplatin showed very promising survival in patients with Stage III NSCLC, especially in those without supraclavicular nodal involvement, which warrants further evaluation.     

Induction chemotherapy with carboplatin/paclitaxel followed by surgery or standard radiotherapy and concurrent daily low-dose cisplatin for locally advanced non-small cell lung cancer (NSCLC)

Five-year survival in patients with unresectable non-small-cell lung cancer (NSCLC) is less than 10%. In the present phase II study, 43 patients with locally advanced stage IIIA or selected IIIB NSCLC were given four courses of carboplatin AUC = 6 and paclitaxel 200 mg/m2 (3-hour infusion), every 3 weeks. Responsive patients, when possible, underwent surgery followed by standard radiotherapy (50 Gy) or radiotherapy (60 Gy), with concurrent cisplatin as intravenous continuous infusion of 4 mg/m2/d. Sixteen of the 42 evaluable patients achieved partial response (38%) and 3 complete response (CR) (7%) for an overall response rate of 45% (95% CI 30.1-60.2). R0 resectability rate was 29%, with 21% of pathologic CRs. Three more CRs were achieved with concurrent chemoradiotherapy in responsive but unresected patients. Grade III/IV hematologic toxicity was 9%, while one perioperative death occurred. The median duration of response was 14 months (range: 3-44+); median survival was 15 months (range: 9-47+). One-year and 2-year survival rates were 51% and 22%, respectively. The median survival in the responsive resected patients was 26 months, with 2-year survival of 57%. Carboplatin/paclitaxel represents an effective and well-tolerated induction therapy, suggesting its possible role in combination with radiotherapy as neoadjuvant treatment in locally advanced NSCLC in alternative to cisplatin-based regimens.     

Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): a feasibility study

BACKGROUND: Concurrent chemoradiotherapy has improved survival in inoperable stage III non-small cell lung cancer (NSCLC). This phase I trial was performed in order to establish a dose recommendation for oral vinorelbine in combination with cisplatin and simultaneous radiotherapy. PATIENTS AND METHODS: Previously untreated patients with stage IIIB NSCLC received concurrent chemoradiotherapy with 66 Gy and 2 cycles of cisplatin and oral vinorelbine which was administered at 3 different levels (40, 50 and 60 mg/m2). This was to be followed by 2 cycles of cisplatin/ vinorelbine oral consolidation chemotherapy. The study goal was to determine the maximal recommended dose of oral vinorelbine during concurrent treatment. RESULTS: 11 stage IIIB patients were entered into the study. The median radiotherapy dose was 66 Gy. Grade 3-4 toxicity included neutropenia, esophagitis, gastritis and febrile neutropenia. The dose-limiting toxicity for concurrent chemoradiotherapy was esophagitis. 9 patients received consolidation chemotherapy, with neutropenia and anemia/thrombocytopenia grade 3 being the only toxicities. The overall response was 73%. CONCLUSION: Oral vinorelbine 50 mg/m2 (days 1, 8, 15 over 4 weeks) in combination with cisplatin 20 mg/m2 (days 1-4) is the recommended dose in combination with radiotherapy (66 Gy) and will be used for concurrent chemoradiotherapy in a forthcoming phase III trial testing the efficacy of consolidation chemotherapy in patients not progressing after chemoradiotherapy.     

TPF方案诱导化疗联合替吉奥同步放疗治疗局部晚期鼻咽癌的临床观察

目的 探讨TPF方案诱导化疗联合替吉奥（S-1）同步调强适形放疗（IMRT）治疗局部晚期鼻咽癌的临床疗效及安全性。方法采用诱导化疗联合S-1同步IMRT治疗38例局部晚期鼻咽癌患者,诱导化疗采用TPF方案：紫杉醇（PTX）135 mg/m2,静滴,d1;顺铂（DDP）80 mg/m2静滴,d1;氟尿嘧啶（5 FU）750 mg/（m2&#8226;d）,持续静脉泵入,d1～d5（120 h）。21天为1个周期,共行2个周期。同步化疗采用替吉奥（S-1）单药,40 mg/m2,口服,2次/日,d1～d14。21天为1个周期,共行2～3个周期。同步放疗PGTVnx（69.96～73.92）Gy/33 f,PGTVnd 69.96 Gy/33 f,PTV1 60.06 Gy/33 f,PTV2 50.96 Gy/28 f,PTVnd 50.96 Gy/28 f,1次/日,5次/周。结果 38例患者均完成2个周期诱导化疗和2～3个周期同步放化疗。所有患者治疗结束评价即刻疗效,获CR 29例,PR 8例,SD 1例,有效率（RR）为974%。治疗结束3个月评价近期疗效,获CR 33例,PR 5例,RR为100%。诱导化疗的主要毒副反应为恶心、白细胞减少、血红蛋白减少。同步放化疗的主要毒副反应为口腔黏膜炎、放射野内皮炎、吞咽痛。其中3级口腔黏膜炎、放射野内皮炎、吞咽痛的发生率分别为7.9%、2.6%、2.6%,均无4、5级毒副反应。结论TPF方案诱导化疗同步替吉奥化疗联合IMRT治疗鼻咽癌,近期疗效好,且毒副反应较小,患者耐受性好。     

Cisplatin and weekly docetaxel with concurrent thoracic radiotherapy for locally advanced stage III non-small-cell lung cancer

Purpose  Our objective was to assess the efficacy and toxicity of concurrent chemoradiotherapy with cisplatin + weekly divided-dose docetaxel in patients with stage III non-small-cell lung cancer (NSCLC). Methods  A total of 34 patients aged less than 75 years old with locally advanced stage III NSCLC were enrolled. The patients received intravenous infusions of cisplatin (80 mg/m²; day 1) and docetaxel (20 mg/m²; days 1, 8, 15), followed by a week’s drug-free interval. Standard concurrent thoracic radiotherapy was given for 6 weeks (2 Gy per fraction; total dose, 60 Gy). Results  Over Grade 3 neutropenia, esophagitis and pulmonary toxicities were observed in 23.5, 17.6 and 11.8% of the cases, respectively. One complete response and 20 partial responses were obtained, with an objective response rate of 61.8%. The median survival time was 26.4 months (95% CI 16.9—not reached) and the 1- and 3-year survival rates were 76.5 and 41.2%, respectively. Conclusion  Cisplatin + weekly docetaxel with concurrent radiotherapy is a feasible and effective regimen for locally advanced NSCLC.     

不可手术局部晚期NSCLC隔周恩度联合同步放化疗多中心五年生存分析

目的:评价隔周使用重组人血管内皮抑制素(恩度)联合以铂类为基础同步放化疗治疗不可手术局部晚期非小细胞肺癌(NSCLC)患者的5年生存情况。方法:2009—2015年间来自两项前瞻性研究的115例患者[2009—2012年临床试验(ClinicalTrials.gov,编号NCT01218594)和2012—2015年的...     

Integrating concurrent navelbine and cisplatin to hyperfractionated radiotherapy in locally advanced non-small cell lung cancer patients treated with induction and consolidation chemotherapy: feasibility and activity results

OBJECTIVES: The purpose of this study was to determine the effectiveness and toxicity of a new combination schedule based on concurrent navelbine, cisplatin and hyperfractionated radiotherapy in patients with locally advanced NSCLC treated with platinum and gemcitabine induction and consolidation chemotherapy. MATERIALS AND METHODS: The 37 patients with pathological confirmed advanced NSCLC (non-surgical stages IIIA and IIIB) were included in the study. All of them were assessable for survival and 32 for response. The treatment schedule consisted of cisplatin (100 mg/m2) or carboplatin (400 mg/m2) on day 1 with gemcitabine (1000 mg/m2) on days 1, 8 and 15. Treatment was given every 28 days for two courses, followed by concurrent administration of accelerated modified hyperfractionated radiotherapy, with concomitant boost, with a total dose of 61.64 Gy administered for 5 weeks, with cisplatin and navelbine, for two courses, finally followed by two courses of the same initial chemotherapy. RESULTS: Four patients achieved complete response (12.5%) and 14 (44%) partial response, for an overall objective response rate of 56.5%. After a minimum follow-up duration of 35.5 months, median progression free survival was 12.2 months. The median survival was 15.4 months with actuarial 1-, 2- and 3-year survival of 67, 21 and 15%, respectively. The main toxicity was hematological. There was esophagitis (grades III and IV) in 30% of the patients and there were two treatment-related deaths. CONCLUSION: Combined treatment with concurrent radiotherapy and chemotherapy in non-surgical NSCLC is an acceptable treatment modality. However, the toxicity was not negligible.     

Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-small-cell lung cancer: phase II Southwest Oncology Group Study S9504.

PURPOSE: To test the concept of taxane sequencing in combined-modality therapy, this phase II trial (S9504) evaluated consolidation docetaxel after concurrent chemoradiotherapy in patients with pathologically documented stage IIIB non-small-cell lung cancer (NSCLC). Results were compared with those of the predecessor study (S9019) with identical eligibility, staging criteria, and treatment, excepting docetaxel consolidation. PATIENTS AND METHODS: Treatment consisted of cisplatin 50 mg/m2 on days 1, 8, 29, and 36, etoposide 50 mg/m2 on days 1 through 5 and 29 through 33, and concurrent thoracic radiotherapy (total dose of 61 Gy). Consolidation docetaxel started 4 to 6 weeks after chemoradiotherapy at an initial dose of 75 mg/m2. RESULTS: Stage subsets (tumor-node-metastasis system) in 83 eligible patients were as follows: T4N0/1, 31 patients (37%); T4N2, 22 patients (27%), and T1-3N3, 30 patients (36%). Concurrent chemoradiotherapy was generally well tolerated, but two patients died from probable radiation-associated pneumonitis. Neutropenia during consolidation docetaxel was common (57% with grade 4) and most frequent during escalation to 100 mg/m2. Median progression-free survival was 16 months, median survival was 26 months, and 1-, 2-, and 3-year survival rates were 76%, 54%, and 37%, respectively. Brain metastasis was the most common site of failure. In S9019, median survival was 15 months and 1-, 2-, and 3-year survival rates were 58%, 34%, and 17%, respectively. CONCLUSION: Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB NSCLC is feasible and generally tolerable, and results compare favorably with the predecessor trial S9019. Nevertheless, this study remains hypothesis-generating and does not provide definitive evidence of the benefit of this approach. Phase III trials evaluating the S9504 regimen have been initiated to validate these results.     

Functional polymorphisms of the microsomal epoxide hydrolase gene: a reappraisal on a early-onset lung cancer patients series

As concomitant chemoradiotherapy for stage III NSCLC is associated with survival advantage in comparison to a sequential approach, we conducted a phase III randomised study aiming to determine the best sequence and safety of chemotherapy (CT) and chemoradiotherapy (CT-RT), using a regimen with cisplatin (CDDP), gemcitabine (GEM) and vinorelbine (VNR). Unresectable stage III NSCLC patients received CDDP (60 mg/m(2)), GEM (1g/m(2), days 1 and 8) and VNR (25mg/m(2), days 1 and 8) with reduced dosage of GEM and VNR during radiotherapy (66Gy). Two cycles of CT with radiotherapy followed by two further cycles of CT alone were administered in arm A or the reverse sequence in arm B. The study was prematurely closed for poor accrual due to administrative problems. Forty-nine eligible patients were randomised. Response rates and median survival times were, respectively 57% (95% CI: 36-78%) and 17 months (95% CI: 9.3-24.6 months) in arm A and 79% (95% CI: 64-94%) and 23.9 months (95% CI: 13.3-34.5 months) in arm B (p>0.05). Chemotherapy dose-intensity was significantly reduced in arm A. Grade 3-4 oesophagitis occurred in 5 patients. One case of grade 5 radiation pneumonitis was observed. In conclusion, chemoradiotherapy with CDDP, GEM and VNR appears feasible as initial treatment or after induction chemotherapy. Consolidation chemoradiotherapy seems less toxic with a better observed response rates and survival although no valid conclusion can be drawn from the comparison of both arms.     

TP诱导化疗后同期放化疗治疗局部晚期鼻咽癌27例的Ⅱ期临床试验

[目的]探索TP方案诱导化疗后DDP同期放化疗治疗局部晚期鼻咽癌的疗效、毒副反应。[方法]2005年12月至2006年12月,27例T3~4N2~3M0鼻咽癌患者纳入试验。诱导化疗采用TP方案(docetaxel 70mg/m2,d1;DDP 80mg/m2,d2),每3周1次,共2个周期。同期化疗采用DDP80mg/m2,d1;放疗采用直线加速器,CT-Sim技术,常规分割。[结果]TP诱导化疗毒副反应主要为血液毒性,同期放化疗毒副反应主要为血液毒性和口腔黏膜反应。TP诱导化疗后鼻咽部病灶缓解率66.7%,区域淋巴结缓解率78.8%。同期放化疗后鼻咽部病灶及区域淋巴结缓解率为100%,其中鼻咽部病灶完全缓解率96.3%;区域淋巴结完全缓解率91.3%。患者1年OS、PFS均为100%。[结论]TP方案诱导化疗后,DDP同期放化疗的毒副反应患者能耐受,近期疗效好。     

Phase I trial of concurrent thoracic radiation and continuous infusion cisplatin and etoposide in stage III non-small cell lung cancer.

OBJECTIVE: Although combined modality therapy appears to be superior to radiotherapy alone for the treatment of locally advanced non-small cell lung cancer (NSCLC), the optimal treatment regimen has not been determined. We designed this trial to determine the maximal tolerated doses (MTD) of continuous intravenous infusion (CI) cisplatin and etoposide that could be administered concurrently with thoracic irradiation. METHODS: 19 patients with stage IIIA or IIIB NSCLC were treated at three different dose levels of CI cisplatin and etoposide with concurrent single daily fraction thoracic radiotherapy to 4500 cGy. This chemoradiotherapy phase of treatment was followed by a 1500-2000 cGy radiotherapy boost and three cycles of standard intermittent bolus cisplatin 80 mg/m2 i.v. on day 1 and etoposide 80 mg/m2 i.v. on days 1, 2 and 3. RESULTS: The MTD of CI chemotherapy was determined to be cisplatin 5 mg/m2/day plus etoposide 18 mg/m2/day for 5 days per week over 5 weeks along with thoracic irradiation. Overall, 37% of patients required breaks in the chemoradiotherapy course and 32% required attenuation of the planned duration of CI chemotherapy. Only 42% of patients received all three planned cycles of bolus chemotherapy and 16% received < 6000 cGy of thoracic irradiation. The major toxicities during concurrent chemoradiotherapy were grade 3-4 esophagitis (42%) and myelosuppression (47%). Subsequent chemotherapy was complicated by grade 3-4 myelosuppression in 38% of patients. An objective response was documented in 58% of patients (CR 11%, PR 47%). Median survival was 18 months with 2- and 5-year survival rates of 42 and 11%, respectively. CONCLUSIONS: These results demonstrate that CI cisplatin and etoposide can be administered safely to patients with locally advanced NSCLC, and that such potentially radiosensitizing strategies deserve further evaluation in this setting.