Randomized phase II trial of uracil/tegafur and cisplatin versus pemetrexed and cisplatin with concurrent thoracic radiotherapy for locally advanced unresectable stage III non-squamous non-small cell lung cancer: NJLCG1001

Kana Watanabe; Yukihiro Toi; Atsushi Nakamura; Ryosuke Chiba; Masachika Akiyama; Jun Sakakibara-Konishi; Hisashi Tanaka; Naruo Yoshimura; Eisaku Miyauchi; Taku Nakagawa; Ryotaro Igusa; Hiroyuki Minemura; Yoshiaki Mori; Keisuke Fujimoto; Haruo Matsushita; Fumiaki Takahashi; Tatsuro Fukuhara; Akira Inoue; Shunichi Sugawara; Makoto Maemondo; North Japan Lung Cancer Study Group, Sendai, Japan

doi:10.21037/tlcr-20-721

Randomized phase II trial of uracil/tegafur and cisplatin versus pemetrexed and cisplatin with concurrent thoracic radiotherapy for locally advanced unresectable stage III non-squamous non-small cell lung cancer: NJLCG1001

Transl Lung Cancer Res. 2021 Feb;10(2):712-722. doi: 10.21037/tlcr-20-721.

Authors

Kana Watanabe¹, Yukihiro Toi², Atsushi Nakamura², Ryosuke Chiba³, Masachika Akiyama³, Jun Sakakibara-Konishi⁴, Hisashi Tanaka⁵, Naruo Yoshimura⁶, Eisaku Miyauchi⁷, Taku Nakagawa⁸, Ryotaro Igusa⁹, Hiroyuki Minemura¹⁰, Yoshiaki Mori¹¹, Keisuke Fujimoto¹², Haruo Matsushita¹³, Fumiaki Takahashi¹⁴, Tatsuro Fukuhara¹, Akira Inoue¹⁵, Shunichi Sugawara², Makoto Maemondo³; North Japan Lung Cancer Study Group, Sendai, Japan

Affiliations

¹ Department of Respiratory Medicine, Miyagi Cancer Center, Natori, Japan.
² Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan.
³ Division of Pulmonary Medicine, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan.
⁴ First Department of Medicine, Hokkaido University Hospital, Sapporo, Japan.
⁵ Department of Respiratory Medicine, Hirosaki University, Hirosaki, Japan.
⁶ Department of Respiratory Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
⁷ Department of Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan.
⁸ Department of Thoracic Surgery, Omagari Kosei Medical Center, Daisen, Japan.
⁹ Department of Respiratory Medicine, Osaki Citizen Hospital, Osaki, Japan.
¹⁰ Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, Fukushima, Japan.
¹¹ Department of Respiratory Medicine, Iwate Prefectural Central Hospital, Morioka, Japan.
¹² Department of Radiation Oncology, Miyagi Cancer Center, Natori, Japan.
¹³ Department of Radiation Oncology, Tohoku University School of Medicine, Sendai, Japan.
¹⁴ Department of Information Science, Iwate Medical University, Morioka, Japan.
¹⁵ Department of Palliative Medicine, Tohoku University School of Medicine, Sendai, Japan.

Abstract

Background: The optimal regimen for concurrent chemoradiotherapy (CCRT) of locally advanced non-squamous non-small cell lung cancer (NSCLC) was not definitive. We conducted randomized phase II study, NJLCG0601, and chemoradiotherapy with uracil/tegafur (UFT) and cisplatin achieved promising efficacy without severe toxicities. Here, we evaluated between this regimen and pemetrexed plus cisplatin in chemoradiotherapy for stage III non-squamous NSCLC.

Methods: Patients with inoperable stage III non-squamous NSCLC were randomly assigned in a 1:1 ratio to UFT 400 mg/m² on days 1-14 and 29-42, and cisplatin 80 mg/m² on days 8 and 36 (UP), or cisplatin 75 mg/m² and pemetrexed 500 mg/m² on days 1, 22, and 43 (PP). Involved-field radiotherapy (IFRT) underwent from day 1 to a total dose of 66 Gy in 33 fractions. Consolidation chemotherapy after CCRT was prohibited for this study. The primary endpoint was defined as 2-year overall survival (OS). This trial was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000003948).

Results: From November 2010 to June 2017, 86 patients were entered from 11 institutions. Median follow-up was 54 months. Of the 85 eligible patients, the 2-year OS rate was 78.6% (95% CI, 62.8-88.3%) in UP and 85.5% (95% CI, 70.5-93.2%) in PP. Median PFS and OS was 12.3 and 64.2 months in UP, 26.2 months and not reached in PP, respectively. Grade 3/4 febrile neutropenia was more frequent in the UP group (14.0% vs. 2.0%).

Conclusions: Both UP and PP with IFRT achieved the expected 2-year OS. PP engendered more favorable OS and PFS compared to UP in terms.

Keywords: Concurrent chemoradiotherapy (CCRT); involved-field radiotherapy (IFRT); non-squamous non-small cell lung cancer (NSCLC); pemetrexed; uracil/tegafur (UFT).