Feasibility study of first-line chemotherapy using Pemetrexed and Bevacizumab for advanced or recurrent nonsquamous non-small cell lung cancer in elderly patients: TORG1015

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Abstract

Background

The addition of bevacizumab to cytotoxic agents prolongs survival in patients with nonsquamous non-small cell lung cancer (NSCLC). To date, there is no evidence to suggest that treatment with a cytotoxic agent plus bevacizumab is more effective than a cytotoxic agent alone for nonsquamous NSCLC in elderly patients. We conducted a feasibility study of pemetrexed plus bevacizumab as a first-line treatment for advanced or recurrent nonsquamous NSCLC in elderly patients.

Methods

Major eligibility and exclusion criteria included: chemotherapy-naive status; non-fitness for bolus combination chemotherapy; stage III/IV or relapsed nonsquamous NSCLC; age ≥70; performance status 0–1; absence of brain metastasis; and no history of hemoptysis and thoracic irradiation. Pemetrexed (500 mg/m ²) and bevacizumab (15 mg/kg) were administered intravenously on day 1, and repeated every 3 weeks thereafter. The primary endpoint was safety, and the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the percentage of patients who completed ≥3 cycles.

Results

From October 2010 to April 2012, a total of 12 patients were enrolled. No dose-limiting toxicity or treatment-related deaths were observed. Three patients achieved PR, and the ORR was 25 %. The median PFS and OS were 5.4 months (95 % CI 1.1–8.8 months) and 13.6 months (95 % CI 5.3–15.6 months), respectively. Seven of 12 patients (58 %) received ≥3 cycles.

Conclusions

Pemetrexed plus bevacizumab in the treatment of elderly patients with nonsquamous NSCLC was well tolerated and shows promise as first-line treatment.

Trial registration

UMIN Clinical Trial Registry; UMIN000004263. Registered on 25 September, 2010.

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Most cited references 12

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Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil.

Martin Reck, Joachim von Pawel, Petr Zatloukal … (2009)

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, improves survival when combined with carboplatin/paclitaxel for advanced nonsquamous non-small-cell lung cancer (NSCLC). This randomized phase III trial investigated the efficacy and safety of cisplatin/gemcitabine (CG) plus bevacizumab in this setting. Patients were randomly assigned to receive cisplatin 80 mg/m2 and gemcitabine 1,250 mg/m(2) for up to six cycles plus low-dose bevacizumab (7.5 mg/kg), high-dose bevacizumab (15 mg/kg), or placebo every 3 weeks until disease progression. The trial was not powered to compare the two doses directly. The primary end point was amended from overall survival (OS) to progression-free survival (PFS). Between February 2005 and August 2006, 1,043 patients were randomly assigned (placebo, n = 347; low dose, n = 345; high dose, n = 351). PFS was significantly prolonged; the hazard ratios for PFS were 0.75 (median PFS, 6.7 v 6.1 months for placebo; P = .003) in the low-dose group and 0.82 (median PFS, 6.5 v 6.1 months for placebo; P = .03) in the high-dose group compared with placebo. Objective response rates were 20.1%, 34.1%, and 30.4% for placebo, low-dose bevacizumab, and high-dose bevacizumab plus CG, respectively. Duration of follow-up was not sufficient for OS analysis. Incidence of grade 3 or greater adverse events was similar across arms. Grade > or = 3 pulmonary hemorrhage rates were < or = 1.5% for all arms despite 9% of patients receiving therapeutic anticoagulation. Combining bevacizumab (7.5 or 15 mg/kg) with CG significantly improved PFS and objective response rate. Bevacizumab plus platinum-based chemotherapy offers clinical benefit for bevacizumab-eligible patients with advanced NSCLC.

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Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial.

Jean Trédaniel, O Molinier, B Milleron … (2011)

Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer (NSCLC) in fit, non-elderly adults, but monotherapy is recommended for patients older than 70 years. We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC. In this multicentre, open-label, phase 3, randomised trial we recruited patients aged 70-89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0-2. Patients received either four cycles (3 weeks on treatment, 1 week off treatment) of carboplatin (on day 1) plus paclitaxel (on days 1, 8, and 15) or five cycles (2 weeks on treatment, 1 week off treatment) of vinorelbine or gemcitabine monotherapy. Randomisation was done centrally with the minimisation method. The primary endpoint was overall survival, and analysis was done by intention to treat. This trial is registered, number NCT00298415. 451 patients were enrolled. 226 were randomly assigned monotherapy and 225 doublet chemotherapy. Median age was 77 years and median follow-up was 30.3 months (range 8.6-45.2). Median overall survival was 10.3 months for doublet chemotherapy and 6.2 months for monotherapy (hazard ratio 0.64, 95% CI 0.52-0.78; p<0.0001); 1-year survival was 44.5% (95% CI 37.9-50.9) and 25.4% (19.9-31.3), respectively. Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group (most frequent, decreased neutrophil count (108 [48.4%] vs 28 [12.4%]; asthenia 23 [10.3%] vs 13 [5.8%]). Despite increased toxic effects, platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC. We feel that the current treatment paradigm for these patients should be reconsidered. Intergroupe Francophone de Cancérologie Thoracique, Institut National du Cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

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Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial.

Francovito Piantedosi, Giampietro Gasparini, Federico Castiglione … (2003)

Vinorelbine prolongs survival and improves quality of life in elderly patients with advanced non-small-cell lung cancer (NSCLC). Some studies have also suggested that gemcitabine is well tolerated and effective in such patients. We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label, randomized phase III trial in elderly patients with advanced NSCLC. Patients aged 70 years and older, enrolled between December 1997 and November 2000, were randomly assigned to receive intravenous vinorelbine (30 mg/m(2) of body surface area), gemcitabine (1200 mg/m(2)), or vinorelbine (25 mg/m(2)) plus gemcitabine (1000 mg/m(2)). All treatments were delivered on days 1 and 8 every 3 weeks for a maximum of six cycles. The primary endpoint was survival. Survival curves were drawn using the Kaplan-Meier method and analyzed by the Mantel-Haenszel test. Secondary endpoints were quality of life and toxicity. Of 698 patients available for intention-to-treat analysis, 233 were assigned to receive vinorelbine, 233 to gemcitabine, and 232 to vinorelbine plus gemcitabine. Compared with each single drug, the combination treatment did not improve survival. The hazard ratio of death for patients receiving the combination treatment was 1.17 (95% confidence interval [CI] = 0.95 to 1.44) that of patients receiving vinorelbine and 1.06 (95% CI = 0.86 to 1.29) that of patients receiving gemcitabine. Although quality of life was similar across the three treatment arms, the combination treatment was more toxic than the two drugs given singly. The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC.

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Author and article information

Contributors

Toshiyuki Kozuki: +81-89-999-1111 , +81-89-999-1100 , tokozuki@shikoku-cc.go.jp

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 12 May 2016

Publication date PMC-release: 12 May 2016

Publication date Collection: 2016

Volume: 16

Electronic Location Identifier: 306

Affiliations

[ ]Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, 160 Kou Minamiumemoto, Matsuyama, Ehime 791-0280 Japan

[ ]Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan

[ ]Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan

[ ]Department of Oncology, Japanese Red Cross Medical Center, Tokyo, Japan

[ ]Department of Biostatistics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan

[ ]Thoracic Oncology Research Group, Yokohama, Japan

Article

Publisher ID: 2338

DOI: 10.1186/s12885-016-2338-6

PMC ID: 4866483

PubMed ID: 27177035

SO-VID: 0ccdb14b-f1da-42d4-a803-7c3917bd7a7a

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 2 February 2016

Date accepted : 5 May 2016

Funding

Funded by: Self-funding

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: non-small cell lung cancer,bevacizumab,pemetrexed,elderly,feasibility study

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: non-small cell lung cancer, bevacizumab, pemetrexed, elderly, feasibility study

Feasibility study of first-line chemotherapy using Pemetrexed and Bevacizumab for advanced or recurrent nonsquamous non-small cell lung cancer in elderly patients: TORG1015

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Abstract

Background

Methods

Results

Conclusions

Trial registration

Related collections

Karger: Oncology

Most cited references 12

Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil.

Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial.

Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial.

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