Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer: a randomized, multicenter phase III trial.

PURPOSE: To compare the overall survival (OS) of patients with advanced non-small-cell lung cancer (NSCLC) treated with docetaxel plus cisplatin (DC) or docetaxel (D) alone. PATIENTS AND METHODS: Chemotherapy-na?ve patients with advanced/metastatic NSCLC were randomly assigned to receive either DC (n = 167; docetaxel 100 mg/m(2) on day 1, cisplatin 80 mg/m(2) on day 2, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) 150 microg/m(2)/d on days 3 to 9) or D (n = 152; 100 mg/m(2) on day 1 without rhG-CSF) every 3 weeks. RESULTS: The overall response rates were 36.5% for DC (three complete responses and 58 partial responses) and 21.7% for D (one complete response and 32 partial responses; P =.004). The median OS was 10.5 months (range, 0.5 to 41 months) and 8.0 months (range, 0.5 to 41 months) for DC and D, respectively (P =.200). The 1- and 2-year survival rates were 44% and 19% for DC and 43% and 15% for D, respectively. Median times to tumor progression were 4.0 and 2.5 months for DC and D, respectively (P =.580). Grade 2/3 anemia was significantly higher with DC than with D (33% v 16%; P =.0001). Fifteen (9%) DC and 12 (8%) D patients developed febrile neutropenia. Grade 3/4 nausea/vomiting (P =.0001), diarrhea (P =.007), neurotoxicity (P =.017), and nephroroxicity (P =.006) were significantly more common with DC than with D. There were five treatment-related deaths in the DC group and one in the D (P =.098). CONCLUSION: DC regimen resulted in a higher response rate but without improvement in median time to tumor progression or OS compared with D. D could be a reasonable front-line chemotherapy for patients who cannot tolerate cisplatin.     

Meta-analysis of docetaxel-based doublet versus docetaxel alone as second-line treatment for advanced non-small-cell lung cancer

Purpose  

To compare docetaxel-based doublet with single-agent docetaxel as second-line treatment in non-small-cell lung cancer (NSCLC).     

Irinotecan plus gemcitabine vs irinotecan for the second-line treatment of patients with advanced non-small-cell lung cancer pretreated with docetaxel and cisplatin: a multicentre, randomised, phase II study

To compare irinotecan (CPT-11)+gemcitabine vs CPT-11 alone as second-line treatment for patients with advanced non-small cell lung cancer (NSCLC) progressing after docetaxel-cisplatinum-based therapy. A total of 147 evaluable, pretreated patients, with NSCLC, received either gemcitabine (1000 mg m(-2), days 1 and 8)+CPT-11 (300 mg m(-2), day 8) (Group A, n=76) or CPT-11 (300 mg m(-2), day 1) (Group B, n=71), every 3 weeks. All patients were evaluable for response and toxicity. The objective response rate was 18.4% (95% CI: 9.71-27.14%) and 4.2% (95% CI: 0-8.90%) (P=0.009) for groups A and B, respectively. No significant differences between the two groups in terms of the median duration of response, time to tumour progression, overall survival and 1-year survival were observed. The CPT-11/gemcitabine regimen significantly improved the patients' quality of life ('general mood today' (P=0.014), 'coughing' (P=0.003) and 'intensity of symptoms' (P=0.034)) compared with CPT-11. More cycles had to be delayed (P=0.001) and required prophylactic growth factor support (P=0.001) in Group A than B. Three (3.9%) patients in Group A and eight (11.3%) in Group B developed febrile neutropenia (P=0.09); one patient died of sepsis in each group. Three additional (Group A, n=1; Group B, n=2) treatment-related deaths were observed. Grade 3-4 haematologic toxicity was comparable in the two groups except anaemia (P=0.03 in favour of CPT-11). Other nonhaematologic toxicities were mild and similar in the two groups. CPT-11+gemcitabine resulted in a higher response rate and better control of disease-related symptoms than CPT-11 alone, but without any improvement in the overall survival.     

多西他赛联合异环磷酰胺方案与多西他赛单药方案二线治疗晚期非小细胞肺癌

背景与目的：多西他赛（多西紫杉醇．进口药泰索帝．TXT）单药是晚期非小细胞肺癌二线治疗的标准治疗。本研究探讨多西他赛联合异环磷酰胺（IFO）方案与多西他赛单药治疗晚期非小细胞肺癌的疗效和不良反应。方法：随机对照研究56例非小细胞肺癌病例：共设立两组，T组：多西他赛单药方案；TI组：多四他赛联合异环磷酰胺方案。结果：PR：T组6例（23．0%）；TI组7例（23．3％）：NC：T组9例（34．6％）；TI组14例（46．7％）。PD：T组8例（30．8％）；TI组8例（26．7%）：NE：T组3例（11．5％）；TI组1例（3．3％）。两组相比．差异无显著性（P=0．6425）．1年生存率：T组21．2％；TI组22．0％。中位生存期：T组237．0d；TI组226．0d。两组相比。差异无显著性（P=0．8815）。中位肿瘤进展时间：T组157．1d；TI组69．8d：差异有显著统性（P=0．0039）。T组Ⅲ／Ⅳ度血小板减少为53．8％，TI组为16．7％。差异有非常显著性（P=0．0056）。T组Ⅲ／Ⅳ度中性粒细胞减少为65．4％．TI组为33．3％．差异有显著性（P=0．0137）。结论：多西他赛联合异环磷酰胺方案在非小细胞肺癌二线治疗中是安全、有效的。但是与多西他赛单药方案比较。有效率和生存期差异均无显著性。     

Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III randomized trial.

PURPOSE To compare the activity and tolerability of docetaxel/gemcitabine (DG) and vinorelbine/cisplatin (VC) combinations in chemotherapy-naive non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Patients with advanced NSCLC were randomly assigned to receive either DG (gemcitabine 1,000 mg/m(2) [days 1 and 8] plus docetaxel 100 mg/m(2) [day 8]) or VC (vinorelbine 30 mg/m(2) [days 1 and 8] plus cisplatin 80 mg/m(2) [day 8]) and prophylactic recombinant human granulocyte colony-stimulating factor (150 microg/m(2) subcutaneously [day 9 through 15]) every 3 weeks. Results A total of 413 randomly assigned patients were analyzed for response and toxicity (DG, n = 197; VC, n = 192). Median survival was 9.0 and 9.7 months (P = .965) for DG and VC arms, respectively; the corresponding 1-year survival rates were 34.3% and 40.8%, respectively. Overall response rate was 30% (95% CI, 23.9% to 36.3%) and 39.2% (95% CI, 32.5% to 45.9%; P = .053) for DG and VC, respectively. Toxicity was as follows (DG v VC): grade 2 to 4 anemia, 34% v 55% (P = .0001); grade 3 to 4 neutropenia, 16% v 37% (P = .0001); febrile neutropenia, 6% v 11% (P = .009); and grade 3 to 4 nausea and vomiting, 1% v 15% (P = .003). Nephrotoxicity occurred in 8% and ototoxicity in 2% of VC-treated patients. There were five and six treatment-related deaths in the DG and VC arms, respectively. Quality of life was improved in DG but not in VC patients. CONCLUSION Although the two regimens produced comparable overall survival, the DG regimen had a better toxicity profile. Therefore, DG could be used in the first-line setting of advanced NSCLC, especially for patients who cannot tolerate cisplatin.     

Gemcitabine as second-line treatment for advanced non-small-cell lung cancer: A phase II trial.

PURPOSE: To investigate the activity and toxicity of gemcitabine as a single agent in patients with advanced non-small-cell lung cancer (NSCLC) after recurrence or failure of previous treatment with a platinum-containing regimen. PATIENTS AND METHODS: From November 1995 to October 1997, 83 patients with stage IIIB or IV NSCLC received gemcitabine 1,000 mg/m(2) once a week for 3 weeks every 28 days. Responses were assessed every two treatment courses. The median age of the patients was 63 years; Eastern Cooperative Oncology Group performance status was 0 to 1 in 62 patients and 2 in 21 patients. The predominant histology was squamous (39 patients); 49 patients had stage IV disease and 34 patients had stage III disease (33 stage IIIB and one stage IIIA). RESULTS: Sixteen patients (19%) achieved a partial response to treatment; the median duration of response was 29 weeks (range, 6 to 50 weeks). Treatment was well tolerated: grade 2 to 3 (World Health Organization standardized response criteria) leukopenia and thrombocytopenia occurred in 23% and 20% of patients, respectively. Mild asthenia was observed in 16% of patients, and peripheral edema in 5% of patients. Nausea and vomiting were present in 16% of patients. CONCLUSION: In this experience, gemcitabine showed significant activity without relevant toxicity, mainly in patients who were previously responsive to chemotherapy. This suggests a possible role for gemcitabine as a second-line treatment in patients who had a previous response or achieved stable disease with a platinum-containing regimen.     

多西他赛联合替吉奥对比多西他赛单药二线冶疗晚期非小细胞肺癌临床观察

目的 探讨多西他赛联合替吉奥对比多西他赛单药二线冶疗晚期非小细胞肺癌的临床疗效.方法 收集经一线治疗后进展的晚期非小细胞肺癌患者100例,参照抽签法将患者随机分为试验组和对照组,每组各50例.试验组患者行多西他赛(60 mg/m2,静滴1 h,第1天)联合替吉奥(40 mg/m2,早晚饭后各服1次,连服14 d,每3周重复)治疗;对照组患者行多西他赛单药治疗(75 mg/m2,静滴1 h,第1天,每3周重复),所有患者随访至疾病进展或死亡.对比两组患者的临床疗效、生存情况及不良反应发生情况.结果 试验组患者的疾病控制率(72.00%)高于对照组患者(56.00%)(P﹤0.05);两组患者的客观缓解率比较,差异无统计学意义(P﹥0.05);试验组患者的中位无进展生存期为4.6个月(95%CI:3.994~5.206)长于对照组患者的3.1个月(95%CI:2.494~3.706)(P﹤0.05);试验组患者的中位生存期为9.2个月(95%CI:8.871~10.529)长于对照组患者的7.9个月(95%CI:5.575~10.225)(P﹤0.05);两组患者各种不良反应发生率及总不良反应发生率比较,差异均无统计学意义(P﹥0.05).结论 多西他赛联合替吉奥二线治疗晚期非小细胞肺癌的临床疗效优于多西他赛单药治疗.     

Phase III trial of docetaxel plus gemcitabine versus docetaxel in second-line treatment for non-small-cell lung cancer: results of a Japan Clinical Oncology Group trial (JCOG0104)

BackgroundThis trial evaluated whether a combination of docetaxel and gemcitabine provides better survival than docetaxel alone in patients with previously treated non-small-cell lung cancer (NSCLC).Patients and methodsEligibility included pathologically or cytologically proven NSCLC, failure of one platinum-based regimen, performance status of zero or one, 20–75 years old, and adequate organ function. Patients received docetaxel 60 mg/m² (day 1) or docetaxel 60 mg/m² (day 8) and gemcitabine 800 mg/m² (days 1 and 8), both administered every 21 days until disease progression.ResultsSixty-five patients participated in each arm. This trial was terminated early due to an unexpected high incidence of interstitial lung disease (ILD) and three treatment-related deaths due to ILD in the combination arm. Docetaxel plus gemcitabine compared with docetaxel-alone patients experienced similar grade and incidence of toxicity, except for ILD. No baseline factor was identified for predicting ILD. Median survival times were 10.3 and 10.1 months (one-sided P = 0.36) for docetaxel plus gemcitabine and docetaxel arms, respectively.ConclusionDocetaxel alone is still the standard second-line treatment for NSCLC. The incidence of ILD is higher for docetaxel combined with gemcitabine than for docetaxel alone in patients with previously treated NSCLC.     

Phase II randomised trial comparing docetaxel given every 3 weeks with weekly schedule as second-line therapy in patients with advanced non-small-cell lung cancer (NSCLC).

BACKGROUND: Taxotere (docetaxel) at the dose of 75 mg/m(2) every 3 weeks is a standard therapy for pretreated non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the safety profile of two schedules of docetaxel administration (every 3 weeks versus weekly) in patients with pretreated NSCLC. PATIENTS AND METHODS: From February 2000 to February 2001, 125 patients with locally advanced or metastatic NSCLC were randomised after failure of a previous platinum-based regimen to receive either docetaxel 75 mg/m(2) administered every 3 weeks (Dq3w) or docetaxel 40 mg/m(2) given weekly for 6 weeks followed by 2 weeks of rest (Dqw). Safety evaluations focused on grade 3-4 neutropenia, febrile neutropenia, nausea-vomiting and asthenia. RESULTS: Patients' characteristics were well balanced between arms. The most common National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3-4 toxicity was neutropenia, which occurred in 48.4% of Dq3w patients versus 15.9% of Dqw patients (P=0.001). In addition, febrile neutropenia were observed in 6.5% of patients in Dq3w versus 0% in Dqw. Grade 3-4 asthenia was more frequent in Dqw. Other non-haematological toxicities were very rare. Regarding efficacy, there was a trend towards a better disease control rate in Dq3w: 32.2% versus 25.4% in Dqw. Median time to progression and survival were rather similar in both arms, respectively: 2.1 months (range 2-3.2) and 5.8 months (range 4.0-7.0) in Dq3w and 1.8 months (range 1.6-2.3) and 5.5 months (range 3.7-6.6) in Dqw. CONCLUSIONS: While both schedules had a favourable safety profile, a significant lower rate of severe neutropenia was observed in the weekly arm. Both regimens had similar efficacy. The weekly regimen could be considered as a good alternative for patients at risk of severe neutropenia.     

SELECT-2: a phase II,double-blind,randomized, placebo-controlled study to assess the efficacy of selumetinib plus docetaxel as a second-line treatment of patients with advanced or metastatic non-small-cell lung cancer

BackgroundCombination of selumetinib plus docetaxel provided clinical benefit in a previous phase II trial for patients with KRAS-mutant advanced non-small-cell lung cancer (NSCLC). The phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC.Patients and methodsPatients who had disease progression after first-line anti-cancer therapy were randomized (2 : 2 : 1) to selumetinib 75 mg b.i.d. plus docetaxel 60 or 75 mg/m² (SEL + DOC 60; SEL + DOC 75), or placebo plus docetaxel 75 mg/m² (PBO + DOC 75). Patients were initially enrolled independently of KRAS mutation status, but the protocol was amended to include only patients with centrally confirmed KRAS wild-type NSCLC. Primary end point was progression-free survival (PFS; RECIST 1.1); statistical analyses compared each selumetinib group with PBO + DOC 75 for KRAS wild-type and overall (KRAS mutant or wild-type) populations.ResultsA total of 212 patients were randomized; 69% were KRAS wild-type. There were no statistically significant improvements in PFS or overall survival for overall or KRAS wild-type populations in either selumetinib group compared with PBO + DOC 75. Overall population median PFS for SEL + DOC 60, SEL + DOC 75 compared with PBO + DOC 75 was 3.0, 4.2, and 4.3 months, HRs: 1.12 (90% CI: 0.8, 1.61) and 0.92 (90% CI: 0.65, 1.31), respectively. In the overall population, a higher objective response rate (ORR; investigator assessed) was observed for SEL + DOC 75 (33%) compared with PBO + DOC 75 (14%); odds ratio: 3.26 (90% CI: 1.47, 7.95). Overall the tolerability profile of SEL + DOC was consistent with historical data, without new or unexpected safety concerns identified.ConclusionThe primary end point (PFS) was not met. The higher ORR with SEL + DOC 75 did not translate into prolonged PFS for the overall or KRAS wild-type patient populations. No clinical benefit was observed with SEL + DOC in KRAS wild-type patients compared with docetaxel alone. No unexpected safety concerns were reported.Trial identifierClinicaltrials.gov NCT01750281.