A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer.

BACKGROUND: The purpose of this study is to determine whether in advanced non-small-cell lung cancer (NSCLC), the sequential administration of cisplatin-based chemotherapy and paclitaxel (Taxol) is superior to a cisplatin-based chemotherapy, followed by paclitaxel as salvage treatment. PATIENTS AND METHODS: A total of 485 chemotherapy naive patients with advanced NSCLC were treated with three courses of GIP (gemcitibine + ifosfamide + cisplatin), consisting of cisplatin 50 mg/m(2) on day 1, ifosfamide 3 g/m(2) on day 1 and gemcitabine 1 g/m(2) on days 1 and 8. Patients with nonprogressive disease were then randomised to further similar courses of GIP or courses of paclitaxel (225 mg/m(2) over 3 h every 3 weeks). RESULTS: Objective response or nonprogression after induction GIP occurred in 174 and 115 patients, respectively. After randomisation, there were 140 patients in the GIP arm and 141 in the paclitaxel arm. In terms of postrandomisation survival, there was no statistically significant difference (P = 0.17) between the two arms. Median times were 9.7 [95% confidence interval (CI) 7.8-11.6] and 11.9 (95% CI 9.4-14.3) months for paclitaxel and GIP, respectively. Multivariate analysis demonstrated that sex and haemoglobin were independent prognostic factors. After adjustment for these factors, the observed hazard ratio was 0.81 (95% CI 0.63-1.04) in favour of GIP (P = 0.10). Toxicity was tolerable; there was a significantly higher rate of grades III/IV thrombocytopenia with GIP and more alopecia with paclitaxel. CONCLUSION: Sequential chemotherapy using cisplatin-based regimen followed by paclitaxel does not result in better outcome than cisplatin-based chemotherapy using taxane as salvage treatment.     

Randomised phase II study of docetaxel/cisplatin vs docetaxel/irinotecan in advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group Study (WJTOG9803)

Docetaxel plus cisplatin and docetaxel plus irinotecan are active and well-tolerated chemotherapy regimens for advanced non-small-cell lung cancer (NSCLC). A randomised phase II study compared their efficacy and toxicity in 108 patients with stage IIIb/IV NSCLC, who were randomised to receive docetaxel 60 mg m(-2) and cisplatin 80 mg m(-2) on day 1 (DC; n=51), or docetaxel 60 mg m(-2) on day 8 and irinotecan 60 mg m(-2) on day 1 and 8 (DI; n=57) every 3 weeks. Response rates were 37% for DC and 32% for DI patients. Median survival times and 1- and 2-year survival rates were 50 weeks (95% confidence interval: 34-78 weeks), 47 and 25% for DC, and 46 weeks (95% confidence interval: 37-54 weeks), 40 and 18% for DI, respectively. The progression-free survival time was 20 weeks (95% confidence interval: 14-25 weeks) with DC and 18 (95% confidence interval: 12-22 weeks) with DI. Significantly more DI than DC patients had grade 4 leucopenia and neutropenia (P<0.01); more DC patients had grade >/=2 thrombocytopenia (P<0.01). Nausea and vomiting was more pronounced with DC (P<0.01); diarrhoea was more common with DI (P=0.01). Three treatment-related deaths occurred in DC patients. In conclusion, although the DI and DC regimens had different toxicity profiles, there was no significant difference in survival.     

First-line treatment of advanced non-small-cell lung cancer with docetaxel and cisplatin: A multicenter phase II study

Purpose: To evaluate the efficacy and safety of the docetaxel-cisplatin combination in patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods: Chemotherapy-naïve patients with histologically confirmed, measurable stage IIIB or IV NSCLC, a World Health Organization (WHO) performance status of 0–2 and adequate bone marrow, renal, hepatic and cardiac function were eligible for the study. Patients received docetaxel (100 mg/m²) as an one-hour infusion on day 1 and cisplatin (80 mg/m²) as a 30-min infusion with appropriate hydration on day 2. Granulocyte colony-stimulating factor (G-CSF; 150 µg/m² , SC) was given on days 3 to 13. Treatment was repeated every three weeks.Results: Fifty-three patients were enrolled (28 with stage IIIB and 25 with stage IV). One complete and 23 partial responses were observed (overall response rate (OR): 45%; 95% CI: 34.1%–61.8%). The response rate was 57% and 32% in patients with stages IIIB and IV disease (P = NS). The median time to progression was 36 weeks and the median survival 48 weeks; the one-year survival was 48%. Grade 3–4 neutropenia occurred in 23 patients, 15 of whom were hospitalized for neutropenic fever; two patients died of sepsis. Grade 2 neurotoxicity was observed in six patients and grade 3 in five patients; grade 3 fatigue occurred in seven patients, grade 3–4 mucositis in four patients and grade 3–4 diarrhea in six patients. Mild allergic reactions and oedema were observed in five and four patients, respectively. The median dose intensity was 30 mg/m² /week for docetaxel and 24 mg/m² /week for cisplatin, corresponding to 91% and 89% of the specified protocol doses, respectively.Conclusions: The docetaxel–cisplatin combination is an active regimen in advanced NSCLC, but hematologic toxicity remains high despite the prophylactic use of G-CSF.     

改进的多西紫杉醇联合顺铂方案治疗晚期非小细胞肺癌的临床观察

目的目前临床上广泛应用多西紫杉醇联合顺铂作为晚期非小细胞肺癌（NSCLC）的一线化疗方案，但传统3wk方案毒副反应较大。因此本研究为比较多西紫杉醇联合顺铂改进的3wk方案与传统3wk方案治疗晚期NSCLC的疗效、毒副反应及1a生存率。方法68例经组织学或细胞学确诊的Ⅲb或Ⅳ期NSCLC病人，随机分为两组，分别接受改进方案（A组）和传统3wk方案（B组）化疗。A组：多西紫杉醇总剂量按75mg／m^2，分2次分别于d1、d8，静脉滴注；每天顺铂25mg／m^2，静脉滴注，dl-d3，每3wk重复；B组：多西紫杉醇75mg／m^2，静脉滴注，d1，顺铂用法同A组，每3wk重复。2周期后评价疗效与毒副反应，并随访la生存率。结果两组均无CR，A组PR10例，SD20例，PD4例，总有效率为29.4％；B组PR11例，SD20例，PD3例，总有效率为32.4％；A组1a生存率为38．2％，B组1a生存率为35.3％，两组疗效（P=0．793）及1a生存率（P=0．801）差异无显著性。中性粒细胞Ⅲ／Ⅳ度减少A组17．6％；B组47．1％，两组差异有显著性（P=0．010）。结论多西紫杉醇联合顺铂改进的3wk方案治疗NSCLC与传统3wk方案相比，疗效相似，但血液学毒性明显下降，耐受性好。     

A randomised phase II trial of docetaxel vs docetaxel and irinotecan in patients with stage IIIb-IV non-small-cell lung cancer who failed first-line treatment

Response rate and toxicity of second-line therapy with docetaxel (75 mg m(-2)) or docetaxel, irinotecan, and lenogastrim (60 mg m(-2), 200 mg m(-2), and 150 microg m(-2) day(-1), respectively) were compared in 108 patients with stage IIIb-IV non-small-cell lung cancer. Addition of irinotecan to docetaxel does not improve response rate, and increases gastrointestinal toxicity.     

改良的多西紫杉醇联合顺铂3周方案一线治疗晚期非小细胞肺癌

背景与目的：目前临床上广泛应用多西紫杉醇联合顺铂作为晚期非小细胞肺癌（NSCLC）的一线化疗方案,但传统3周方案毒副反应较大。因此本研究为比较多西紫杉醇联合顺铂改进的3周方案与传统3周方案一线治疗晚期NSCLC的疗效及毒副反应。方法：68例经组织学或细胞学确诊的ⅢB或Ⅳ期NSCLC患者,随机分为两组分别接受改进方案（A组）和传统3周方案（B组）化疗。A组：多西紫杉醇总剂量按75 mg/m^2,分两次分别于第1、8天,静脉滴注顺铂25 mg/（m^2.d）,静脉滴注,第1天~第3天,每3周重复;B组：多西紫杉醇75 mg/m^2,静脉滴注,第1天,顺铂用法同A组,每3周重复。2周期后评价疗效与毒副反应,并随访1年生存率。结果：两组均无CR,A组PR 10例,SD 20例,PD 4例,总有效率为29%;B组PR 11例,SD 20例,PD 3例,总有效率为32%;A组1年生存率为38%,B组1年生存率为35%,两组疗效（P=0.793）及1年生存率（P=0.801）差异无显著性。中性粒细胞Ⅲ/Ⅳ度减少A组18%;B组47%,两组差异有显著性（P=0.010）。结论：多西紫杉醇联合顺铂改进的3周方案一线治疗NSCLC与传统3周方案相比,疗效相似,但血液学毒性明显下降,耐受性好。     

国产多西紫杉醇治疗非小细胞肺癌的Ⅱ期临床研究

目的 :评价国产多西紫杉醇 (艾素 ,江苏恒瑞医药股份有限公司产品 )单用以及艾素 +顺铂联合化疗方案对非小细胞肺的临床疗效和安全性 ,并以进口多西紫杉醇 (泰索帝 ,安万特公司产品 ) +顺铂联合化疗方案作对照。方法 :患者随机分入艾素单用组 (A组 ) :艾素 75mg/m2 ;艾素 +顺铂组 (B组 ) :艾素 75mg/m2 +顺铂 75mg/m2 ;泰索帝 +顺铂组 (C组 ) :泰索帝 75mg/m2 +顺铂 75mg/m2 ;3组均为每 3周重复。结果 :入组的 115例中 10 4例可评价疗效 ,A、B和C组有效率分别为 8 10 %、2 3 5 3%、2 7 2 7%。B和C组有效率相似。不良反应主要有中性粒细胞减少、贫血、粒细胞减少性发热、其他发热、脱发、恶心呕吐和乏力。C组中性粒细胞减少的发生率高于B组 ,两组间差异有显著性 (P <0 0 5 )。其余不良反应两组相似。结论 :国产多西紫杉醇 (艾素 ) +顺铂与进口多西紫杉醇 (泰索帝 ) +顺铂两联合化疗方案相似 ,对非小细胞肺癌有一定疗效 ,且毒性可耐受。     

多西紫杉醇联合顺铂辅助化疗对非小细胞肺癌的疗效及不良反应影响

目的 探究多西紫杉醇联合顺铂辅助化疗对非小细胞肺癌的疗效以及不良反应影响.方法 回顾性分析246例非小细胞肺癌患者的临床资料.按照不同的治疗方式分为对照组和研究组,对照组采用多西紫杉醇治疗,研究组采用多西紫杉醇联合顺铂治疗,对比两组的近期治疗有效率,不良反应发生率以及功能状态改善情况.结果 研究组近期总有效率为51.22%显著高于对照组29.26%(P﹤0.01);两组发生的各项不良反应(如:恶心呕吐、疲乏无力、白细胞减少等)率均无明显差异(P﹥0.05);两组治疗后,功能状态评分均得到显著提高,研究组提高幅度更大(P﹤0.01);两组患者1年、2年生存率的比较均无明显差异(P﹥0.05).结论 多西紫杉醇联合顺铂辅助化疗对非小细胞肺癌的疗效甚佳,并且不会增加不良反应,还可以改善患者的功能状态,具有临床实际应用价值.     

多西紫杉醇联合顺铂治疗Ⅲ～Ⅳ期NSCLC临床研究

目的:观察多西紫杉醇联合顺铂化疗方案治疗Ⅲ~Ⅳ期非小细胞肺癌(NSCLC)的临床疗效、生存期及毒副反应。方法:Ⅲ~Ⅳ期NSCLC患者62例,多西紫杉醇75mg/m2,静脉点滴,d1;顺铂75mg/m2,静脉点滴,d1~3。21天为1疗程,至少治疗3周期。结果:总有效率为43.5%(27/62,均为部分缓解),Karnofsky计分增加或不变者占67.4%,中位缓解期为7个月。主要毒副反应为骨髓抑制,Ⅲ~Ⅳ度白细胞下降占16.1%,无Ⅲ~Ⅳ度血红蛋白和血小板下降。非血液学毒性轻微。结论:多西紫杉醇与顺铂联合给药方案治疗NSCLC有较好疗效,耐受性好。     

Sequential two-line strategy for stage IV non-small-cell lung cancer: docetaxel-cisplatin versus vinorelbine-cisplatin followed by cross-over to single-agent docetaxel or vinorelbine at progression: final results of a randomised phase II study.

BACKGROUND: This phase II trial compared docetaxel-cisplatin (DC) with vinorelbine-cisplatin (VC), both as first-line therapy followed by cross-over at progression to single-agent vinorelbine or docetaxel in advanced non-small-cell lung cancer (NSCLC). METHODS: Overall, 115 patients received DC (docetaxel 75 mg/m(2) and cisplatin 100 mg/m(2) both on day 1, every 3 weeks, arm A1) and 118 VC (vinorelbine 30 mg/m(2)/week on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, arm B1) for six cycles, and subsequently maintained by monotherapy with docetaxel (A1) or vinorelbine (B1) with cross-over on disease progression to vinorelbine 30 mg/m(2) days 1 and 8 (A2), or docetaxel 100 mg/m(2), day 1, both every 3 weeks (B2). The primary end point was overall response rate (ORR). RESULTS: Patient characteristics were balanced; median follow-up was 8.8 months. First-line response rate was 33.9% with DC and 26.3% with VC (P=0.20). In arms A1 and B1, respectively: duration of response was similar (8.2 versus 8.4 months); median time to progression was 5 months in both; median survival was 8 versus 9 months (P=0.38); 1-, 2- and 3-year survival was 36% versus 35%, 17% versus 10% and 13% versus 6% (P not significant). However, with a low number of long-term survivors, statistical significance was not reached. Overall, almost half of the patients crossed over to second-line therapy; there were no response with vinorelbine and 6 (11.2%) partial responses with docetaxel. Considering the safety profile, the occurrence of febrile neutropenia was 9.6% with DC and 26.3% with VC. Treatment-related mortality was 2.5% with DC and 8.5% with VC. CONCLUSIONS: The trend in favour of the DC arm in ORR, even though statistical significance was not reached, is consistent with previous reports. This study suggests an activity of first-line DC in advanced NSCLC, and that second-line vinorelbine does not provide additional clinical benefit. As already shown in other studies, the use of DC in first-line should provide a better percentage of long-term survivors, despite the absence of efficacy of the second-line in our study.     

Randomized phase II trial of gemcitabine plus irinotecan or docetaxel in stage IIIB or stage IV NSCLC.

BACKGROUND: To evaluate the activity and tolerability of gemcitabine plus irinotecan or docetaxel as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients with chemotherapy-na?ve stage IIIB or IV NSCLC were randomized to receive gemcitabine 1000 mg/m2 on days 1 and 8, plus either irinotecan 100 mg/m2 or docetaxel 40 mg/m2 on days 1 and 8. Treatment was administered every 3 weeks. RESULTS: Of the 80 enrolled patients with stage IIIB or IV NSCLC, 78 were evaluable for activity and safety. Overall response rates, consisting of partial responses, were 12.8% [95% confidence interval (CI) 4% to 35%] for gemcitabine-irinotecan and 23.1% (95% CI 10% to 42%) for gemcitabine-docetaxel. Median overall survival was 7.95 months (95% CI 5.2-10.2) and 12.8 months (95% CI 7.9-17.1) for gemcitabine-irinotecan and gemcitabine-docetaxel, respectively. The corresponding estimated 1-year survivals were 23% and 51%, respectively. The 2-year survival rate in arm A (gemcitabine-irinotecan) is not currently estimable. The 2-year survival rate for arm B (gemcitabine-docetaxel) is 22% (95% CI 6% to 37%). Both combinations were well tolerated; the most common hematological toxicity was neutropenia, which occurred in 26% of patients in each treatment arm. CONCLUSIONS: These results suggest that gemcitabine plus docetaxel or irinotecan is well tolerated in patients with chemotherapy-na?ve advanced NSCLC. The survival data with the combination gemcitabine-docetaxel are promising. Gemcitabine-docetaxel combination therapy may be particularly useful for patients who have experienced toxicities with a platinum regimen or in patients who may be more susceptible to platinum-related toxicity.     

Multicenter phase II trial of docetaxel and carboplatin in patients with stage IIIB and IV non-small-cell lung cancer

Purpose:To evaluate the safety and efficacy of docetaxel andcarboplatin as first-line therapy for patients with advanced non-small-celllung cancer (NSCLC). Patients and methods:In this multicenter, phase II trial, 33patients with previously untreated stage IIIB (n = 8) or IV(n = 25) NSCLC received intravenous infusions of docetaxel 80mg/m² followed immediately by carboplatin dosed to AUC of 6mg/ml/min (Calvert's formula) every three weeks. Patients also receiveddexamethasone 8 mg orally twice daily for three days beginning one day beforeeach docetaxel treatment. Filgrastim was not allowed during the first cycleand was added only if a patient experienced febrile neutropenia or grade 4neutropenia lasting 7 days. Results:There were 1 complete and 11 partial responses for anobjective response rate of 43% (95% CI:24%–63%) in 28 evaluable patients and 36%(95% CI: 20%–55%) in the intent-to-treatpopulation. The median duration of response was 5.5 months (range3.0–12.5 months). The median survival was 13.9 months (range 1–35+months); one-year survival was 52%. The most common toxicity washematologic, which included grade 4 neutropenia (79% of patients and7% percent of cycles) and febrile neutropenia (15% of patients);there were no episodes of grade 3 or 4 infection. The most common severenonhematologic toxicities were asthenia (24%) and myalgia (12%);there were no grade 3 or 4 neurologic effects. Conclusions:The combination of docetaxel and carboplatin has anacceptable toxicity profile and is active in the treatment of previouslyuntreated patients with advanced NSCLC. This combination is being evaluatedin a randomized phase III trial involving patients with advanced andmetastatic NSCLC.     

多西紫杉醇联合顺铂治疗晚期非小细胞肺癌32例疗效观察

目的:观察多西紫杉醇(docetaxel,TXT) 顺铂(cisplatin,DDP)联合治疗晚期非小细胞肺癌(NSCLC)的临床疗效和毒副作用。方法:对32例晚期NSCLC患者采用TXT联合DDP方案化疗:TXT35mg/m2,ivgtt,d1,8,15;DDP25mg/m2,ivgtt,d1~3,每28天重复,至少治疗2个周期。结果:总有效率46.9%,中位生存期11.3个月,主要毒副作用为骨髓抑制、脱发、恶心和呕吐。结论:TXT联合DDP治疗晚期NSCLC有较好疗效,毒副作用可以耐受。     

A phase I/II study comparing regimen schedules of gemcitabine and docetaxel in Japanese patients with stage IIIB/IV non-small cell lung cancer

OBJECTIVE: Gemcitabine and docetaxel are non-platinum agents with activity in non-small cell lung cancer (NSCLC). This study was conducted to determine and evaluate the recommended regimen of gemcitabine-docetaxel and evaluated its efficacy and safety in chemonaive Japanese NSCLC patients. METHODS: In phase I, patients with stage IIIB/IV NSCLC were randomized and received either gemcitabine on days 1 and 8 plus docetaxel on day 1 or gemcitabine on days 1 and 8 plus docetaxel on day 8. The recommended regimen was the dose level preceding the maximum tolerated dose; once determined, patients were enrolled in phase II. Efficacy and toxicity were evaluated in all patients. RESULTS: Twenty-five patients were enrolled in phase I and six patients were given the recommended regimen; gemcitabine 1000 mg/m(2) on days 1 and 8 plus docetaxel 50 mg/m(2) on day 8. An additional 34 patients were enrolled into phase II and administered with the recommended regimen. The response rate was 32.2% [95% confidence interval (CI) 20.6-45.6%] overall and 30.0% (95% CI 16.6-46.5%) in patients with the recommended regimen (40 patients). Although grade 3 interstitial pneumonia was observed in two patients (5.0%) who received the recommended regimen, both recovered shortly after steroid treatment. No unexpected events were observed throughout this study. CONCLUSIONS: Gemcitabine 1000 mg/m(2) on days 1 and 8 plus docetaxel 50 mg/m(2) on day 8 has comparable efficacy and more tolerable toxicities than previously reported platinum-based regimens. These results should be verified by a phase III study.     

Randomized phase II trial of two different schedules of docetaxel plus cisplatin as first-line therapy in advanced nonsmall cell lung cancer

BACKGROUND: There is increasing interest in the use of a weekly administration of docetaxel as a way of reducing its hematologic toxicity. The purpose of the current randomized study was to evaluate the toxicity and efficacy of docetaxel plus cisplatin combination on 2 schedules in patients with previously untreated, advanced nonsmall-cell lung cancer (NSCLC). METHODS: Consenting patients with advanced NSCLC were randomized to receive first-line chemotherapy with cisplatin 75 mg/m(2) on Day 1, plus 3-weekly (75 mg/m(2) on Day 1) or weekly (35 mg/m(2) on Days 1, 8, and 15 of a 4-week cycle) docetaxel, for up to 6 cycles. RESULTS: Of 86 patients accrued, 41 patients were treated with 3-weekly and 43 with weekly docetaxel plus cisplatin. The most frequent grade 3/4 toxicity in the 3-weekly arm was neutropenia (56% of patients). In those receiving the weekly regimen, the frequent grade 3/4 toxicities were fatigue (44%) and nausea/vomiting (35%). The overall response rate was 40% with the 3-weekly and 39% with the weekly arm (P = .74). The median progression-free survival was 4.3 months in the 3-weekly arm and 3.9 months in the weekly arm (P = .08) and the median survival was 10.3 and 10.0 months, respectively (P = .76). Quality of life data showed no relevant difference between the arms. CONCLUSIONS: The weekly schedule of docetaxel plus cisplatin combination as first-line chemotherapy for advanced NSCLC, while feasible, has no clear advantage over the standard 3-weekly regimen.     

A phase II trial of docetaxel plus capecitabine in patients with previously treated non-small cell lung cancer

BACKGROUND: A combination of docetaxel (T) and capecitabine (X) showed synergistic effects in preclinical studies and phase III randomized trials of metastatic breast cancer. We conducted this phase II study to examine its efficacy in previously treated non-small cell lung cancer (NSCLC) patients. METHODS: Patient eligibility required advanced NSCLC with measurable lesion(s), at least one prior regimen failure and Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Treatment consisted of T 36 mg/m(2) i.v. on days 1 and 8 plus X 1000 mg/m(2) p.o. b.i.d. on days 1-14 of a 21-day cycle (level I) or T 30 mg/m(2) i.v. on days 1 and 8 plus X 625 mg/m(2) p.o. b.i.d. on days 1-14 of a 21-day cycle (level II). RESULTS: A total of 35 patients (M/F=24/11) were enrolled; 29 had received one prior regimen and 19 had received platinum-based regimens. Significant non-hematologic toxicities were observed after the treatment given at level I, including one treatment-related death. Subsequently 29 patients were treated at level II. The treatment at level II was well tolerated with grade 3 or 4 neutropenia only in 10%, grade 3 asthenia in 21% and stomatitis in 14% of patients. Four (15%) of 27 evaluable patients had partial response (PR) at level II and eight (30%) had stable disease (SD). CONCLUSIONS: The TX regimen showed modest antitumor effects in patients with previously treated NSCLC. For further studies, we recommend T 30 mg/m(2) i.v. on days 1 and 8 plus X 625 mg/m(2) p.o. b.i.d. on days 1-14 of a 21-day cycle.     

放疗同步多西他赛化疗治疗晚期非小细胞肺癌的临床观察

目的:研究放疗同步多西他赛化疗对晚期非小细胞肺癌的疗效及毒副作用。方法:74例Ⅲ期非小细胞肺癌患者被随机分为两组,放疗同步多西他赛化疗组(放化组),单纯放疗组(单放组);两组放疗方法相同,放疗肿瘤量DT60Gy～65Gy,每次2Gy,每周5次,放化组在放疗同时每周予多西他赛40mg化疗一次。结果:放化组和单放组的有效率分别是81.1%和75.7%(P>0.05),两组的完全缓解率是32.4%和10.8%(P<0.05),放射性肺炎及食管炎发生率放化组高于单放组(P<0.05)。结论:放疗同步多西他赛化疗治疗晚期非小细胞肺癌疗效好,副反应虽增加,但能耐受。     

Comparison of docetaxel and docetaxel-irinotecan combination as second-line chemotherapy in advanced non-small-cell lung cancer: a randomized phase II trial.

BACKGROUND: The aim of this study was to evaluate whether docetaxel (taxotere) treatment with or without irinotecan improved patient outcomes with similar toxicity in recurrent non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with recurrent platinum-refractory NSCLC with Eastern Cooperative Oncology Group performance status of 0-2 were randomized to either docetaxel 30 mg/m(2) and irinotecan 60 mg/m(2) (days 1 and 8) or docetaxel 75 mg/m(2) (day 1), both administered every 3 weeks. RESULTS: A total of 130 patients were randomized. The response rate (RR) (20% versus 14%), overall survival (6.5 months versus 6.4 months) and 1-year survival (37% versus 34%) were similar in the combination and docetaxel arms, respectively. The combination arm demonstrated a longer time to tumor progression (TTP) (5.6 versus 4.8 months; P=0.065). Grade 3-4 neutropenia and anemia were similar in the combination and docetaxel arms. Grades 3-4 non-hematological toxicity (except diarrhea) was mild and was similar in the two groups. Grade 3-4 thrombocytopenia (17% versus 6%; P=0.04) and diarrhea (12% versus 3%; P=0.05) occurred more frequently in the combination arm. CONCLUSIONS: The administration of irinotecan with docetaxel in platinum-refractory NSCLC prolonged TTP, but did not improve significantly RR, median survival or 1-year survival. Second-line docetaxel monotherapy offers significant and reproducible efficacy in platinum-refractory NSCLC.     

A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1).

BACKGROUND: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m(2), carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2) and cisplatin 50 mg/m(2) or mitomycin 6 mg/m(2), vinblastine 6 mg/m(2) and cisplatin 50 mg/m(2), respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. RESULTS: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. CONCLUSIONS: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained.     

A randomised phase II study of docetaxel/oxaliplatin and docetaxel in patients with previously treated non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group trial (ATOM 019)

Introduction

To date, no combination regimen has proven superior to single agent chemotherapy as a second-line treatment for non-small cell lung cancer (NSCLC).

Methods

This multicenter, non-comparative randomised phase II trial evaluated the activity of docetaxel (75 mg/m² on day 1) with oxaliplatin (70 mg/m² on day 2) every 3 weeks in previously treated NSCLC patients; the reference arm was single-agent docetaxel (75 mg/m² on day 1 every 3 weeks). It was designed as a one-stage, three-outcome phase II trial; 21 evaluable patients were required in each arm. The primary end-point was response rate; secondary end-points were toxicity, progression free survival (PFS) and overall survival.

Results

Fifty patients were enrolled. Patient characteristics included male/female, 76/24%; median age 62 years; ECOG PS 0/1, 36/64%; previous platinum-based chemotherapy, 98%. Partial response was seen in 20% and 8%, stable disease in 52% and 32%, of patients treated with docetaxel/oxaliplatin and docetaxel, respectively. Main grade 3-4 toxicities were neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhoea 12% and 4% for docetaxel/oxaliplatin and docetaxel, respectively. Median PFS was 5.0 and 1.7 months, median survival 11.0 and 7.1 months, and 1-year survival 44% and 32% for docetaxel/oxaliplatin and docetaxel, respectively.

Conclusions

The study met its pre-defined study end-point; docetaxel/oxaliplatin and more generally platinum-containing doublets warrant further evaluation as second-line therapy for patients with NSCLC.