A single-arm, phase 2 study of adjuvant chemotherapy with oral tegafur-uracil for pathologically lymphovascular invasion positive stage IA non-small cell lung cancer: LOGIK0602 study

• Published in: BMC cancer 2020-12, Vol.20 (1), p.1192-8, Article 1192
• Main Authors: Tsuchiya, Tomoshi, Kamohara, Ryotaro, Muraoka, Masashi, Nagayasu, Takeshi, Saeki, Sho, Takenoyama, Mitsuhiro, Suzuki, Makoto, Inada, Kazuo, Tokunaga, Shoji, Hayashi, Tomayoshi, Urabe, Shogo, Koga, Takaomi, Akamine, Shinji, Sugio, Kenji
• Format: Article
• Language: English
• Subjects: Adjuvant chemotherapy; Adjuvants, Pharmaceutic; Aged; Angiogenesis; Anorexia; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Blood Vessels - pathology; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; Chemotherapy; Chemotherapy, Adjuvant - adverse effects; Combined Modality Therapy; Compliance; Creatinine; Development and progression; Disease-Free Survival; Drug dosages; Drug therapy; Female; Gastrointestinal Diseases - chemically induced; Humans; Kaplan-Meier Estimate; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Lymphatic metastasis; Lymphatic Vessels - pathology; Lymphovascular invasion; Male; Medical prognosis; Middle Aged; Neoplasm Invasiveness; Neutropenia - chemically induced; Non-small cell lung cancer; Non-small cell lung carcinoma; Patient Compliance; Patient outcomes; Patients; Phase II study; Pneumonectomy; Prodrugs - administration & dosage; Prodrugs - adverse effects; Prospective Studies; Small cell lung carcinoma; Survival analysis; Targeted therapy; Tegafur; Tegafur - administration & dosage; Tegafur - adverse effects; Tegafur-uracil; Uracil; Uracil - administration & dosage; Uracil - adverse effects; Vascular endothelial growth factor
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-020-07691-7

Lymphovascular invasion (LVI), which includes vascular or lymphatic invasions, is a representative prognostic factor even in patients with resected stage IA non-small cell lung cancer (NSCLC). Because tegafur-uracil is effective on cancers with LVI, we conducted a multi-center single-arm phase II study to estimate the efficacy of adjuvant tegafur-uracil in patients with LVI-positive stage IA NSCLC. Patients with completely resected LVI-positive stage IA NSCLC were registered. LVI was diagnosed by consensus of two of three pathologists. Adjuvant chemotherapy consisted of 2 years of oral tegafur-uracil at 250 mg/m /day. Fifty-five patients from 7 institutions were enrolled from June 2007 to September 2012. Among the 52 eligible patients, 36 (69.2%) completed the treatment course. There were 39 male and 13 female patients. The observation period was calculated as 562 to 3107 days using the reverse Kaplan-Meier method. The 5-year overall and relapse free survival rates were 94.2 and 88.5% respectively, which were significantly better than that of any other studies conducted on patients with LVI-positive stage IA NSCLC. Notably, the overall survival rate was 15% better than that of our prior retrospective study. The retrospective analysis of stage IA NSCLC patients who had received an operation in the same period revealed that the 5-year overall survival rate of the LVI positive group was 73.6% when adjuvant chemotherapy was not applied. Among 55 safety analysis sets, 4 cases of grade 3 hepatic function disorder (9.1%) and 5 cases of grade 2 anorexia (10.9%) were most frequently observed. No grade 4 adverse effects were encountered. A 2-year course of oral tegafur-uracil administration is feasible and might have a significant benefit in the adjuvant treatment of LVI-positive stage IA NSCLC. UMIN identifier: UMIN000005921 ; Date of enrolment of the first participant to the trial: 19 June 2007; Date of registration: 5 July 2011 (retrospectively registered).