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

Toshiyuki Kozuki,Terufumi Kato,Kentaro Sakamaki,Yuichi Takiguchi,Hiromoto Kitajima,Tetsu Shinkai,Shunichiro Iwasawa,Masahiro Yoshida,Emiko Sakaida,Satoshi Ikeda,Shingo Miyamoto,Koshiro Watanabe,Naoyuki Nogami

doi:10.1186/s12885-016-2338-6

Abstract

BackgroundThe 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.MethodsMajor 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/m2) 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.ResultsFrom 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.ConclusionsPemetrexed plus bevacizumab in the treatment of elderly patients with nonsquamous NSCLC was well tolerated and shows promise as first-line treatment.Trial registrationUMIN Clinical Trial Registry; UMIN000004263. Registered on 25 September, 2010.

Highlights

The addition of bevacizumab to cytotoxic agents prolongs survival in patients with nonsquamous non-small cell lung cancer (NSCLC)
Patients were unfit for bolus administration of cisplatin or combination chemotherapy, and had adequate bone marrow, hepatic, and renal functions (leucocyte counts ≥4000/mm3, absolute neutrophil counts ≥2000/ mm3, platelet counts ≥100,000/mm3, haemoglobin ≥9.5 g/ dl, serum aspartate aminotransferase (AST) ≤2.5× upper limit of normal (ULN) range, alanine aminotransferase (ALT) ≤2.5× ULN, total bilirubin ≤1.5 mg/dl, serum creatinine ≤1.5 mg/dl, and urinalysis of proteinuria by dipstick (dipstick result ≤(+))
If dose-limiting toxicities (DLTs) were observed in ≥4 out of six patients or ≥6 out of 12 patients at level 0, we evaluated the patients as level −1 when pemetrexed dosage was reduced to 375 mg/m2

Summary

Introduction

The addition of bevacizumab to cytotoxic agents prolongs survival in patients with nonsquamous non-small cell lung cancer (NSCLC). We conducted a feasibility study of pemetrexed plus bevacizumab as a first-line treatment for advanced or recurrent nonsquamous NSCLC in elderly patients. There is an urgent need to develop a treatment strategy especially tailored for elderly patients with advanced or recurrent non-small cell lung cancer (NSCLC). Studies showed pemetrexed is an alternative option to third-generation agents, such as gemcitabine or docetaxel, in the treatment of advanced or recurrent NSCLC in a first- or second-line setting [4, 5]. Due to its mild toxicity profile, pemetrexed could represent a promising chemotherapeutic agent for nonsquamous non-small cell malignancy especially for elderly patients

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Conclusion