Vinorelbine Plus Cisplatin Versus Docetaxel Plus Gemcitabine in Advanced Non-Small-Cell Lung Cancer: A Phase III Randomized Trial

2005 ◽  
Vol 23 (13) ◽  
pp. 2937-2945 ◽  
Author(s):  
Vassilis Georgoulias ◽  
Alexandros Ardavanis ◽  
Xanthi Tsiafaki ◽  
Athina Agelidou ◽  
Penelope Mixalopoulou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Survival Rates ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Grade 3 ◽  
Line Setting

Purpose To compare the activity and tolerability of docetaxel/gemcitabine (DG) and vinorelbine/cisplatin (VC) combinations in chemotherapy-naïve 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/m2 [days 1 and 8] plus docetaxel 100 mg/m2 [day 8]) or VC (vinorelbine 30 mg/m2 [days 1 and 8] plus cisplatin 80 mg/m2 [day 8]) and prophylactic recombinant human granulocyte colony-stimulating factor (150 μg/m2 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.

Randomized Phase III Study of Gemcitabine-Cisplatin Versus Etoposide-Cisplatin in the Treatment of Locally Advanced or Metastatic Non–Small-Cell Lung Cancer

1999 ◽  
Vol 17 (1) ◽  
pp. 12-12 ◽  
Author(s):  
Felipe Cardenal ◽  
M. Paz López-Cabrerizo ◽  
Antonio Antón ◽  
Vicente Alberola ◽  
Bartomeu Massuti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non–small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Vinorelbine Plus Cisplatin in the Treatment of Patients With Advanced Non–Small-Cell Lung Cancer: A Southwest Oncology Group Trial

2001 ◽  
Vol 19 (13) ◽  
pp. 3210-3218 ◽  
Author(s):  
Karen Kelly ◽  
John Crowley ◽  
Paul A. Bunn ◽  
Cary A. Presant ◽  
Patra K. Grevstad ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Resource Utilization ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Survival Rates ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE: This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non–small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. PATIENTS AND METHODS: Two hundred two patients received VC (vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m2 over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. RESULTS: Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P = .002) and neutropenia (P = .008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P = .001, P = .007), and grade 3 peripheral neuropathy was higher on the PC arm (P < .001). More patients on the VC arm discontinued therapy because of toxicity (P = .001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs. CONCLUSION: PC is equally efficacious as VC for the treatment of advanced non–small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.

Docetaxel Versus Docetaxel Plus Cisplatin As Front-Line Treatment of Patients With Advanced Non—Small-Cell Lung Cancer: A Randomized, Multicenter Phase III Trial

2004 ◽  
Vol 22 (13) ◽  
pp. 2602-2609 ◽  
Author(s):  
Vassilis Georgoulias ◽  
Alexandros Ardavanis ◽  
Athina Agelidou ◽  
Maria Agelidou ◽  
Vassilis Chandrinos ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Rates ◽  
Complete Response ◽  
Small Cell ◽  
Phase Iii ◽  
Front Line ◽  
Small Cell Lung ◽  
Grade 3

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-naïve patients with advanced/metastatic NSCLC were randomly assigned to receive either DC (n = 167; docetaxel 100 mg/m2 on day 1, cisplatin 80 mg/m2 on day 2, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) 150 μg/m2/d on days 3 to 9) or D (n = 152; 100 mg/m2 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 progession or OS compared with D. D could be a reasonable front-line chemotherapy for patients who cannot tolerate cisplatin.

scholarly journals Current landscape of immunotherapy for the treatment of metastatic non-small-cell lung cancer

2018 ◽  
Vol 25 ◽  
pp. 94 ◽  
Author(s):  
A. Pabani ◽  
C.A. Butts
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Toxicity ◽  
Line Setting

For patients with advanced non-small-cell lung cancer (nsclc) lacking a targetable molecular driver, the mainstay of treatment has been cytotoxic chemotherapy. The survival benefit of chemotherapy in this setting is modest and comes with the potential for significant toxicity. The introduction of immunotherapeutic agents targeting the programmed cell death 1 protein (PD-1) and the programmed cell death ligand 1 (PD-L1) has drastically changed the treatment paradigms for these patients. Three agents—atezolizumab, nivolumab, and pembrolizumab—have been shown to be superior to chemotherapy in the second-line setting. For patients with tumours strongly expressing PD-L1, pembrolizumab has been associated with improved outcomes in the first-line setting.Demonstration of the significant benefits of immunotherapy in nsclc has focused attention on new questions. Combination checkpoint regimens, with acceptable toxicity and potentially enhanced efficacy, have been developed, as have combinations of immunotherapy with chemotherapy. In this review, we focus on the published trials that have changed the treatment landscape in advanced nsclc and on the ongoing clinical trials that offer hope to further improve outcomes for patients with advanced nsclc.

Phase II Study of Pemetrexed and Carboplatin Plus Bevacizumab With Maintenance Pemetrexed and Bevacizumab As First-Line Therapy for Nonsquamous Non–Small-Cell Lung Cancer

2009 ◽  
Vol 27 (20) ◽  
pp. 3284-3289 ◽  
Author(s):  
Jyoti D. Patel ◽  
Thomas A. Hensing ◽  
Alfred Rademaker ◽  
Eric M. Hart ◽  
Matthew G. Blum ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Time Curve ◽  
Grade 3

PurposeThis study evaluated the efficacy and safety of pemetrexed, carboplatin, and bevacizumab followed by maintenance pemetrexed and bevacizumab in patients with chemotherapy-naive stage IIIB (effusion) or stage IV nonsquamous non–small-cell lung cancer (NSCLC).Patients and MethodsPatients received pemetrexed 500 mg/m2, carboplatin area under the concentration-time curve of 6, and bevacizumab 15 mg/kg every 3 weeks for six cycles. For patients with response or stable disease, pemetrexed and bevacizumab were continued until disease progression or unacceptable toxicity.ResultsFifty patients were enrolled and received treatment. The median follow-up was 13.0 months, and the median number of treatment cycles was seven (range, one to 51). Thirty patients (60%) completed ≥ six treatment cycles, and nine (18%) completed ≥ 18 treatment cycles. Among the 49 patients assessable for response, the objective response rate was 55% (95% CI, 41% to 69%). Median progression-free and overall survival rates were 7.8 months (95% CI, 5.2 to 11.5 months) and 14.1 months (95% CI, 10.8 to 19.6 months), respectively. Grade 3/4 hematologic toxicity was modest—anemia (6%; 0), neutropenia (4%; 0), and thrombocytopenia (0; 8%). Grade 3/4 nonhematologic toxicities were proteinuria (2%; 0), venous thrombosis (4%; 2%), arterial thrombosis (2%; 0), fatigue (8%; 0), infection (8%; 2%), nephrotoxicity (2%; 0), and diverticulitis (6%; 2%). There were no grade 3 or greater hemorrhagic events or hypertension cases.ConclusionThis regimen, involving a maintenance component, was associated with acceptable toxicity and relatively long survival in patients with advanced nonsquamous NSCLC. These results justify a phase III comparison against the standard-of-care in this patient population.

Phase III Trial Comparing Oral S-1 Plus Carboplatin With Paclitaxel Plus Carboplatin in Chemotherapy-Naïve Patients With Advanced Non–Small-Cell Lung Cancer: Results of a West Japan Oncology Group Study

2010 ◽  
Vol 28 (36) ◽  
pp. 5240-5246 ◽  
Author(s):  
Isamu Okamoto ◽  
Hiroshige Yoshioka ◽  
Satoshi Morita ◽  
Masahiko Ando ◽  
Koji Takeda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Rates ◽  
Area Under The Curve ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Open Label ◽  
Phase Iii Trial

Purpose The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods A total of 564 patients were randomly assigned to receive either carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every 21 days. Results At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of carboplatin and S-1 compared with carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the carboplatin and S-1 arm and 13.3 months in the carboplatin and paclitaxel arm, with 1-year survival rates of 57.3% and 55.5%, respectively. Rates of leukopenia or neutropenia of grade 3/4, febrile neutropenia, alopecia, and neuropathy were more frequent in the carboplatin and paclitaxel arm, whereas thrombocytopenia, nausea, vomiting, and diarrhea were more common in the carboplatin and S-1 arm. The carboplatin and S-1 arm had significantly more dose delays than the carboplatin and paclitaxel arm. Conclusion Oral S-1 with carboplatin was noninferior in terms of OS compared with carboplatin and paclitaxel in patients with advanced NSCLC, and is thus a valid treatment option.

scholarly journals Immunotherapy in non-metastatic non-small cell lung cancer: Can the benefits of stage IV therapy be translated into earlier stages?

2018 ◽  
Vol 10 ◽  
pp. 175883591877281 ◽  
Author(s):  
Griet Deslypere ◽  
Dorothée Gullentops ◽  
Els Wauters ◽  
Johan Vansteenkiste
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Stage Iv ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR) activating mutations or anaplastic lymphoma kinase ( ALK) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC. Aside from chemotherapy and targeted therapy, immunotherapy has become the third pillar in the treatment armamentarium of advanced NSCLC. Antigen-specific immunotherapy (cancer vaccination) has been disappointing in large phase III clinical trials in stages I–III NSCLC. Based on the recent breakthroughs with immune checkpoint inhibitor immunotherapy in metastatic NSCLC, much hope currently rests on the use of this approach in patients with stage I–III NSCLC as well. Here we give a brief overview of how most new therapeutic approaches for advanced NSCLC failed in other stages, and then elaborate on the role of immunotherapy in patients with stage I–III NSCLC.

Treatment of Non-Small Cell Lung Cancer: Focus on Pemetrexed Disodium

2010 ◽  
Vol 2 ◽  
pp. CMT.S5262
Author(s):  
Josephine Feliciano ◽  
Jyoti Patel
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Folic Acid Supplementation ◽  
Small Cell ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Line Setting

Pemetrexed (Alimta, Eli Lilly) is a multi-targeted anti-folate originally approved for its use in malignant mesothelioma. Based on results from phase III clinical investigations, it is now approved for use as a single agent in the second-line setting and in combination with platinum therapy in the first-line setting for advanced non-small cell lung cancer. It is also under investigation in earlier stages of non small cell lung cancer including in the adjuvant setting and with radiation. It has shown to be particularly efficacious for non-squamous histology and is well tolerated. Toxicity includes, but is not limited to hematologic toxicity and gastrointestinal toxicity, which are minimized by vitamin B12 and folic acid supplementation. Recent analyses also suggest cost-effectiveness of this agent in patient with advanced, non-squamous cell non-small cell lung cancer.

Phase III Study Comparing Amrubicin Plus Cisplatin With Irinotecan Plus Cisplatin in the Treatment of Extensive-Disease Small-Cell Lung Cancer: JCOG 0509

2014 ◽  
Vol 32 (12) ◽  
pp. 1262-1268 ◽  
Author(s):  
Miyako Satouchi ◽  
Yoshikazu Kotani ◽  
Taro Shibata ◽  
Masahiko Ando ◽  
Kazuhiko Nakagawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Phase Iii ◽  
Point Estimate ◽  
Small Cell Lung ◽  
Extensive Disease ◽  
Grade 3

Purpose This randomized phase III trial was conducted to confirm noninferiority of amrubicin plus cisplatin (AP) compared with irinotecan plus cisplatin (IP) in terms of overall survival (OS) in chemotherapy-naive patients with extensive-disease (ED) small-cell lung cancer (SCLC). Patients and Methods Chemotherapy-naive patients with ED-SCLC were randomly assigned to receive IP, composed of irinotecan 60 mg/m2 on days 1, 8, and 15 and cisplatin 60 mg/m2 on day 1 every 4 weeks, or AP, composed of amrubicin 40 mg/m2 on days 1, 2, and 3 and cisplatin 60 mg/m2 on day 1 every 3 weeks. Results A total of 284 patients were randomly assigned to IP (n = 142) and AP (n = 142) arms. The point estimate of OS hazard ratio (HR) for AP to IP in the second interim analysis exceeded the noninferior margin (HR, 1.31), resulting in early publication because of futility. In updated analysis, median survival time was 17.7 (IP) versus 15.0 months (AP; HR, 1.43; 95% CI, 1.10 to 1.85), median progression-free survival was 5.6 (IP) versus 5.1 months (AP; HR, 1.42; 95% CI, 1.16 to 1.73), and response rate was 72.3% (IP) versus 77.9% (AP; P = .33). Adverse events observed in IP and AP arms were grade 4 neutropenia (22.5% v 79.3%), grade 3 to 4 febrile neutropenia (10.6% v 32.1%), and grade 3 to 4 diarrhea (7.7% v 1.4%). Conclusion AP proved inferior to IP in this trial, perhaps because the efficacy of amrubicin as a salvage therapy was differentially beneficial to IP. IP remains the standard treatment for extensive-stage SCLC in Japan.

scholarly journals Efficacy and toxicities of combination maintenance therapy in the treatment of advanced non-small-cell lung cancer: an up-to-date meta-analysis

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Jianming Hu ◽  
Jiawei Hu ◽  
Xiaolan Liu ◽  
Long Li ◽  
Xue Bai
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3 ◽  
Nsclc Patients

Abstract Background: Single agent maintenance therapy has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) due to its potential survival benefits, but whether combined maintenance therapy would improve the survival of advanced NSCLC remains undetermined. Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing combination maintenance therapy in advanced NSCLC patients were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade 3–4 toxicities. Results: A total of 1950 advanced NSCLC patients received combination maintenance treatment from six trials were included for analysis. The use of doublet maintenance therapy in NSCLC patients significantly improved PFS (HR 0.74, 95%CI: 0.59–0.93, P = 0.010), but not for OS (HR 0.95, 95%CI: 0.85–1.07, P = 0.40) in comparison with single agent maintenance therapy. Similar results were observed in sub-group analysis according to treatment regimens. In addition, there was no significantly risk difference between doublet and single agent maintenance therapy in terms of grade 3/4 hematologic and non-hematologic toxicities. Conclusion: The findings of the present study show that doublet combination maintenance therapy is superior to single agent maintenance therapy in terms of PFS, without increased grade 3–4 toxicities. Future prospective studies are recommended to clearly assess the long-term clinical benefit of doublet maintenance therapy and its impact on health-related quality of life.

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