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.     

Randomized phase III study of 3-weekly versus weekly docetaxel in pretreated advanced non-small-cell lung cancer: a Spanish Lung Cancer Group trial.

BACKGROUND: Docetaxel is a widely accepted second-line treatment in advanced non-small-cell lung cancer (NSCLC) with a risk of myelotoxicity. This study evaluated the efficacy and toxicity profile of two docetaxel regimens in NSCLC patients who had failed first-line non-docetaxel-based chemotherapy. PATIENTS AND METHODS: A total of 259 patients from 33 Spanish centers were randomized to receive either docetaxel 75 mg/m(2) administered every 3 weeks (3W arm) or docetaxel 36 mg/m(2) given weekly (1W arm) for 6 weeks followed by 2 weeks of rest. The primary end point was 1-year survival; secondary end points were median survival, time to progression, response and toxicity. RESULTS: One-year survival was 27% in the 3W and 22% in the 1W arm. Median time to progression was also similar in the two arms. Median survival was 6.6 months in the 3W arm versus 5.4 months in the 1W arm (P = 0.075). Response rates were 9.3% in the 3W arm and 4.8% in the 1W arm. More patients in the 1W arm experienced mucositis [1W, nine patients (7.2%); 3W, two patients (1.6%); P = 0.032], while febrile neutropenia was significantly higher in the 3W arm [3W, 10 patients (7.8%); 1W, one patient (0.8%); P = 0.010]. CONCLUSIONS: Both weekly and 3-weekly docetaxel were effective and well-tolerated, with different toxicity profiles. In general, there was no indication to recommend the weekly schedule. However, the significant lower rate of febrile neutropenia observed in the weekly schedule makes it a good alternative for patients at risk of severe neutropenia.     

ALIMTA (pemetrexed disodium) as second-line treatment of non-small-cell lung cancer: a phase II study.

BACKGROUND: The purpose of this study was to evaluate ALIMTA (pemetrexed disodium, LY231514), a multi-targeted antifolate with first-line activity against non-small-cell lung cancer (NSCLC), in a second-line setting. PATIENTS AND METHODS: Patients with NSCLC were eligible for this phase II study if they had progressive disease within 3 months after first-line chemotherapy or progression while being treated with first-line chemotherapy. In 81 patients studied, two cohorts of patients were assigned based on whether the first-line therapy had included a platinum regimen. ALIMTA was administered at 500 mg/m2 by 10-min intravenous infusion once every 21 days. RESULTS: The response rate in the 79 evaluable patients with poor prognostic features was 8.9% [95% confidence interval (CI) 2.6% to 15.1%]. The response rate in the platinum-pretreated group was 4.5% and 14.1% in the non-platinum-pretreated group. The median duration of response was 6.8 months (95% CI 3.4-7.8 months, 0% censoring). The median survival time was 5.7 months (95% CI 4.0-8.3 months, 7.6% censoring). The probability of survival for at least 6 months was estimated to be 48%. The median time to disease progression was 2 months (95% CI 1.4-2.8 months, 0% censoring). The principal toxicity was myelosuppression, which was reversible. CONCLUSIONS: ALIMTA is active in a second-line setting in non-platinum-pretreated NSCLC patients progressing within 3 months of first-line chemotherapy. This study demonstrates that it is possible to evaluate new drugs against NSCLC in a second-line setting.     

Front-line paclitaxel and irinotecan combination chemotherapy in advanced non-small-cell lung cancer: a phase I-II trial

Our purpose was to determine the efficacy of irinotecan plus paclitaxel administered on day 1, repeated every 2 weeks, in untreated patients with advanced or metastatic non-small-cell lung cancer (NSCLC). In total, 56 patients with inoperable or metastatic stage III and IV NSCLC with a histologically or cytologically confirmed diagnosis were enrolled. None of the patients had undergone prior chemotherapy or radiation therapy. Treatment involved irinotecan 125 mg m(-2) and paclitaxel 135 mg m(-2) administered on day 1 and repeated every 2 weeks for a planned number of nine cycles. With a standard dose of paclitaxel at 135 mg m(-2), the dosage of irinotecan was escalated at four levels: 75, 100, 125 and 150 mg m(-2); 125 mg m(-2) was established as the maximum tolerated dose; this dosage was administered to 46 patients. A total of 52 patients (median age 65 years, range 38-77 years) were assessable for toxicity and survival and 46 for response rate. Out of 46 evaluable patients, 19 achieved partial response (41.3%), 17 had stable disease (37%) and 10 (21.7%) experienced disease progression. The median duration of response was 6 months (range 2-9+ months). The main adverse reactions were myelotoxicity (grades 3 and 4) in 10 (19.2%) patients and diarrhoea (grade 3) in four (7.7%) patients. Irinotecan combined with paclitaxel, administered every 2 weeks, appears to be an effective treatment for advanced-stage NSCLC.     

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.     

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。     

Biological agents alone or in combination as second-line therapy in advanced non-small-cell lung cancer: systematic review of randomized studies

The only approved agents for second-line therapy in unselected non-small-cell lung cancer are docetaxel and pemetrexed (chemotherapies) and erlotinib (targeted therapies). Several new molecular drugs have now entered clinical trials and are being compared with approved agents (e.g., vandetanib). Alternative pathways are also being explored to overcome resistance to established agents (c-MET and ALK inhibitors), and predictive factors are now crucial for the selection of drug and of patients (e.g., EGFR mutations). Better patient selection permits second-line treatment to be tailored according to disease identity, which confers a particular benefit in certain subgroups of patients. In this review, the authors examine existing trials comparing targeted therapies with the standard of care as second-line therapy for advanced non-small-cell lung cancer.     

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.     

Gemcitabine and vinorelbine followed by docetaxel in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial of nonplatinum sequential triplet combination chemotherapy (JMTO LC00-02)

To evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC), we conducted the multiinstitutional phase II study. A total of 44 chemotherapy-naive patients with advanced NSCLC were treated with GEM 1000 mg m(-2) and VNR 25 mg m(-2) intravenously on days 1 and 8 every 3 weeks for three cycles. DOC 60 mg m(-2) was then administrated intravenously at 3-week intervals for three cycles. Patients were evaluated for response and toxicity with each cycle of the treatment. The major objective response rate was 47.7% (95% confidence interval (CI), 33.8-62.1%). Median survival time (MST) was 15.7 months and 1-year survival rate was 59%. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 36.3%, grade 3/4 anaemia in two patients (4.5%) and grade 3 thrombocytopenia in one patient (2.3%). Grade 3 pneumonitis occurred in two patients (4.5%) in GEM/VNR cycles. In the DOC cycles, grade 3/4 neutropenia occurred in 39.4% but no patient experienced grade 3/4 anaemia or thrombocytopenia. Of the 44 eligible patients, 33 patients completed three cycles of GEM/VNR and 22 patients completed six cycles of planned chemotherapy (three cycles of GEM/VNR followed by three cycles of DOC). The sequential triplet nonplatinum chemotherapy consisted of GEM/VNR followed by DOC, and was very active and well tolerated. This study forms the basis for an ongoing phase III trial that compares this nonplatinum triplet and standard platinum doublet combination (carboplatin/paclitaxel).     

A phase II study of weekly docetaxel as salvage chemotherapy for advanced gastric cancer

Background:Docetaxel has shown some activity in advanced gastriccancer. Recent phase I studies found low hematologic toxicity and a favourabletoxicity profile when docetaxel was administered on a weekly schedule. In thisstudy, we explored the activity of weekly docetaxel in patients with advancedgastric cancer who failed first-line chemotherapy. Materials and methods:Patients with stable or progressing diseaseafter first-line chemotherapy received 36 mg/m² weekly docetaxel.One cycle consisted of six administrations followed by a two-weeks rest,patients were re-evaluated at week eight. The optimal two-stage design wasadopted for early stopping of the trial if responses were one or less in 21patients (<20% response rate with and errorprobabilities 0.05 and 0.010 respectively). Results:Twenty-one patients have been enrolled and they are fullyevaluable for response and toxicity. One patient achieved partial response,8 patients had stable disease and 12 patients progressed. Median overallsurvival from the onset of salvage chemotherapy was 3.5 months. Hematologictoxicity was observed in two patients who experienced grade III leukopenia.Beginning from the third week of treatment, most of the patients (90%)showed grade II asthenia which resulted the commonest side-effect. Conclusions:This schedule of weekly docetaxel did not showsignificant activity in pretreated patients with advanced gastric cancer.     

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.     

Single-agent gemcitabine in pretreated patients with non-small-cell lung cancer: results of an Argentinean multicentre phase II trial.

The activity and mild toxicity profile of single-agent gemcitabine therapy in untreated (chemonaive) patients with non-small-cell lung cancer (NSCLC) is well documented. This phase II trial was conducted to determine the objective tumour response rate and toxicity profile of single-agent gemcitabine in pretreated patients with NSCLC. Patients with histological evidence of advanced NCSLC stage IIIB or IV; at least one prior chemotherapy regimen including a platinum or taxane analogue; an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; clinically measurable disease; adequate bone marrow reserve; and adequate renal function; received 1000 mg m(-2) gemcitabine administered over 30 min on days 1, 8 and 15 of a 28-day cycle defined as 3 weekly treatments followed by 1 week of rest. Twenty-nine patients were evaluated for efficacy and 32 for toxicity. One patient achieved a complete response and five patients had a partial response resulting in a total response rate of 20.6% (95% confidence interval (CI) 6-34). Median response duration was 7 months (range 4-11 months). Twelve (41%) patients reached stable disease after two cycles of therapy and 11 (38%) patients had disease progression. Median progression-free survival time was 3 months and median overall survival time was 5.5 months. Toxicity was generally mild (grades 0-2). Severe (grade 3 or 4) haematological toxicities included grade 3 anaemia in one patient and grade 3 thrombocytopenia in two patients. Severe non-haematological toxicities included one patient each with grade 3 liver transaminase elevations, nausea/vomiting and diarrhoea. This study confirms the activity and safety of single-agent gemcitabine in pretreated patients with advanced NSCLC who are refractory or sensitive to first-line therapy.     

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.     

Second-line chemotherapy for non-small-cell lung cancer with monthly docetaxel and weekly gemcitabine: A phase II trial

Background:Docetaxel and gemcitabine are active againstchemotherapy-pretreated non-small-cell lung cancer (NSCLC). The purpose ofthis phase II study was to evaluate the efficacy and safety of monthlydocetaxel combined with weekly gemcitabine in NSCLC patients failing one priorregimen. Patients and methods:Forty patients were enrolled. Priorchemotherapy was a platinum-based combination in 36 patients, usingvinorelbine in 26 patients and etoposide in 10 patients. The other fourpatients had prior single agents. Tumors were refractory or resistant tofront-line therapy in 80% of patients. Treatment was gemcitabine 800mg/m² days 1, 8, 15 and docetaxel 100 mg/m² day 1, withcycles repeated every four weeks. Results:Thirteen patients responded (32.5%; 95%confidence interval (CI): 19%–49%), including one completeand 12 partial responses. Responses were observed at all metastatic sites,with similar response frequencies in platinum-sensitive andplatinum-resistant/refractory tumors. The median time to progression forresponders was nine months, with two responses lasting longer than a year.Median survival was 8.1 months. Hematologic toxicities included grade 4neutropenia in 23 patients, with 4 episodes of febrile neutropenia, grade3–4 thrombocytopenia in 9 patients, and anemia requiring red celltransfusions in 9 patients. With the exception of asthenia, severenon-hematologic toxicities were infrequent. Conclusions:Monthly docetaxel, combined with weekly gemcitabine,is an active and safe second-line therapy for NSCLC patients.     

多西紫杉醇联合长春瑞滨二线治疗晚期非小细胞肺癌的临床研究

Objective:To evaluate the efficacy and toxicity of docetaxel and vinorelbine as second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:48 histologically or cytologically confirmed NSCLC patients with progressive or recurrent disease after first-line treatment were treated with docetaxel and vinorelbine.The chemotherapy included vinorelbine (25 mg/m2) on days 1,5 and docetaxel (60 mg/m2) on day 1.The treatment was repeated every 3 weeks.Patients receiving at least two cycles were evaluated for efficacy and toxicity.Results:Of 48 patients,1 patient achieved complete response and 16 achieved partial response.Overall response rate for all 48 patients was 35.4% (17/48).Main hematologic toxicities included neutropenia (60.4%) and febrile neutropenia (29.2%) and non-hematologic toxicities were mild.Conclusion:The combination of docetaxel-vinorelbine as second-line chemotherapy is an effective regimen with manageable toxicity for the treatment of advanced NSCLC.Further studies may confirm these results.     

伊立替康二线治疗晚期食管癌的临床观察

目的：观察伊立替康单药二线治疗23例晚期食管癌患者的临床获益率、中位生存期和毒性反应.方法：采用伊立替康单药方案治疗（140mg/m2,静滴90分钟,第1天;120mg/m2,第8天,每3周给药）.化疗2-4周期后观察临床获益率、中位生存期和毒性反应.结果：23例患者中,PR 2例（8.7％）,SD 11例（47.8％）,临床获益率56.5％.中位PFS为2.3个月,中位生存期为5.7个月.主要毒副反应,Ⅲ-Ⅳ度消化道反应5例（21.7％）,其中腹泻3例.Ⅲ-Ⅳ度血液学毒性4例（17.4％）.结论：对于晚期复发进展的食管癌患者,伊立替康单药方案治疗是安全、有效的二线治疗方案.     

Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin.

BACKGROUND: This multicenter, randomized, phase III study compared the efficacy, including progression-free survival (PFS), and safety of gemcitabine-docetaxel (GD) combination versus cisplatin-vinorelbine (CV) in the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemonaive patients with stage IIIB or IV NSCLC were treated with GD (gemcitabine 1000 mg/m(2) days 1 and 8 plus docetaxel 85 mg/m(2) day 8, every 3 weeks for eight cycles) or CV (cisplatin 100 mg/m(2) day 1 plus vinorelbine 30 mg/m(2), days 1, 8, 15 and 22, every 4 weeks for six cycles). RESULTS: A total of 311 patients were enrolled (155 GD and 156 CV). Neither PFS nor overall survival differed significantly between the two arms (median PFS 4.2 and 4 months; median survival 11.1 and 9.6 months; 1-year survival 46% and 42%, for GD and CV, respectively). For the GD arm compared with the CV arm, the hazard ratio for PFS was 1.04 [95% confidence interval (CI) 0.83-1.32], and for overall survival, it was 0.90 (95% CI 0.70-1.16). Objective response rates did not differ significantly (31% for GD, 35.9% for CV). Myelosupression, emesis and frequency of febrile neutropenia were less pronounced on the GD arm, whereas fluid retention and pulmonary events were more pronounced. The CV arm experienced a higher number of serious adverse events and a lower compliance with the protocol. There was no quality of life (QoL) difference between arms. Median time to definite impairment of health-related QoL was 153 and 168 days in GD and CV arms, respectively. CONCLUSIONS: There was no advantage in PFS with GD compared with CV; however, the CV regimen had higher rate of toxic events, mainly myelosuppression. The herein, non-platinum-containing regimen could be considered as a rational alternative to the cisplatin-based doublet.     

Second-line docetaxel and gemcitabine combination chemotherapy in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy

Docetaxel has been the only single active agent against chemotherapy-pretreated non-small-cell lung cancer (NSCLC). The purpose of this phase II study was to evaluate the efficacy and safety of docetaxel combined with gemcitabine, another effective drug, in patients with NSCLC previously treated with platinum-based chemotherapy. Thirty-three patients were enrolled. Prior chemotherapy was cisplatin combined with etoposide in 24 patients and vinorelbine in 9 patients. Tumors were sensitive (n=15), resistant (n=9), and refractory (n=9) to front-line chemotherapy. Treatment was docetaxel 85 mg/m² on d 1, and gemcitabine 1200 mg/m² on d 1 and 8, with cycles repeated every three weeks. Ten patients (30.3%, 95% CI: 15.6–48.7) achieved a partial response and 15 (45.5%) stable disease. Responses were similar frequencies in platinum-sensitive and platinum-resistant/refractory tumors. With a median follow-up period of 5.7 mo (range 1.6–20.0), the median and 6-mo event-free survival were 5.5 mo, 40.6%, respectively. Median and 6-mo over-all survival were 7.3 mo and 52.7%. Patients with progressive disease to chemotherapy (p=0.0008), higher LDH (p=0.005), and NSE levels (p=0.03) survived shorter than other patients. In patients refractory to prior chemotherapy, survival was poor as borderline significantly (p=0.06). The major hematological toxicity was neutropenia. Grade III–IV neutropenia was noted in 14 (42%) patients, with three episodes of febrile neutropenia in 111 cycles. Docetaxel combined with gemcitabine is an active and safe second-line therapy for patients with NSCLC.     

A multi-center phase II study of nintedanib as second-line therapy for patients with advanced non-small-cell lung cancer in China

Purpose: This study examined the efficacy and safety of using nintedanib as single-regimen in 2^nd-line chemotherapy for Chinese patients with advanced (beyond stage IIIB) non-small-cell lung cancer (NSCLC). Methods: Chinese patients were those with stage IIIB or IV NSCLC and had unsuccessful 1^st-line platinum based chemotherapy. Patients received two oral intakes of 200 mg nintedanib everyday from day 1 to day 21, on every 4-week cycle. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and disease control rate. Results: There were 62 eligible patients enrolled in the study. Half of the patients were male (n = 31, 50.0%). The median age was 64.2 years with youngest age of 33 years and oldest age of 83 years. Median PFS was 3.9 months (95% CI, 2.7-6.4 months). Median OS was 6.7 months (95% CI, 4.8-10.1 months). No patients (0.0%) had complete response. Thirty-one patients (50.0%) had stable disease and 23 patients (37.1%) had partial response. The most common severe adverse events (AEs), graded as 3 or 4, were heart failure (n = 12, 19.4%), hypertension (n = 7, 11.8%) and diarrhea (n = 6, 9.8%). Conclusion: NSCLC Patients in 2^nd-line chemotherapy reached similar PFS, as compared with other FDA-approved second-line regimens. Also, the toxicity of nintedanib was well tolerated. Thus, nintedanib may be used as a standard regimen for 2^nd-line chemotherapy for patients with advanced NSCLC.     

Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer

Background:

Selumetinib (AZD6244, ARRY-142886)+docetaxel increases median overall survival (OS) and significantly improves progression-free survival (PFS) and objective response rate (ORR) compared with docetaxel alone in patients with KRAS mutant, stage IIIB/IV non-small-cell lung cancer (NSCLC; {"type":"clinical-trial","attrs":{"text":"NCT00890825","term_id":"NCT00890825"}}NCT00890825).

Methods:

Retrospective analysis of OS, PFS, ORR and change in tumour size at week 6 for different sub-populations of KRAS codon mutations.

Results:

In patients receiving selumetinib+docetaxel and harbouring KRAS G12C or G12V mutations there were trends towards greater improvement in OS, PFS and ORR compared with other KRAS mutations.

Conclusion:

Different KRAS mutations in NSCLC may influence selumetinib/docetaxel sensitivity.