Yoko Tsukita1, Akira Inoue2, Shunichi Sugawara3, Shoichi Kuyama4, Taku Nakagawa5, Daijiro Harada6, Hisashi Tanaka7, Kana Watanabe8, Yoshiaki Mori9, Toshiyuki Harada10, Toshihiko Hino11, Masanori Fujii12, Masakazu Ichinose1. 1. Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, 980 8574, Japan. 2. Department of Palliative Medicine, Tohoku University School of Medicine, Sendai, 980 8575, Japan. Electronic address: akira.inoue.b2@tohoku.ac.jp. 3. Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, 980 0873, Japan. 4. Department of Respiratory Medicine, Iwakuni Clinical Center, Iwakuni, 740 8510, Japan. 5. Department of Thoracic Surgery, Omagari Kosei Medical Center, Daisen, 014 0027, Japan. 6. Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, 791 0280, Japan. 7. Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, 036 8562, Japan. 8. Department of Respiratory Medicine, Miyagi Cancer Center, Natori, 981 1293, Japan. 9. Division of Respiratory medicine, Iwate Prefectural Central Hospital, Morioka, 020 0066, Japan. 10. Department of Respiratory Medicine, JCHO Hokkaido Hospital, Sapporo, 062 8618, Japan. 11. Department of Respiratory Medicine, Yamagata Prefectural Central Hospital, Yamagata, 990 2292, Japan. 12. Department of Respiratory Medicine, Kobe Red Cross Hospital, Kobe, 651 0073, Japan.
Abstract
OBJECTIVES: Invasive thymoma (IT) and thymic carcinoma (TC) are rare epithelial neoplasms arising in the anterior mediastinum. Platinum-based chemotherapies are widely used for first-line treatment of unresectable IT and TC, but no standard treatment has been established for previously-treated IT and TC thus far. Because promising efficacy of S-1 (tegafur, gimeracil and oteracil combination) has been reported in some retrospective studies, we conducted the first prospective phase II trial to evaluate its efficacy in previously-treated patients with advanced IT and TC. MATERIALS AND METHODS: Patients progressing after at least one regimen of systemic chemotherapy received S-1 orally at a dose based on body surface area for 2 weeks followed by one week of rest until tumor progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profile. We defined an ORR of 25% as indicating potential usefulness while ORR of 10% was the lower limit of interest. RESULTS: Forty patients were enrolled (IT, n = 20; TC, n = 20). ORR was 17.5% (95% CI 7.3-32.8; IT, 10%; TC, 25%), disease control rate was 85% (IT, 95%; TC, 75%). Median PFS was 7.0 months (IT, 11.3 months; TC, 5.4 months), and median OS was 40.3 months (IT, 58.5 months; TC, 22.7 months) with a median follow-up of 51.9 months. Major toxicities (grade 3-4) were anorexia (10%), neutropenia (7.5%) and pneumonitis (5%). No treatment-related death was observed. CONCLUSION: Although the primary endpoint was not met, S-1 monotherapy did have effects similar to recently reported immunotherapies for TC but at much lower cost. S-1 could represent a treatment option for previously-treated advanced TC. This trial was registered as UMIN 000008174.
OBJECTIVES:Invasive thymoma (IT) and thymic carcinoma (TC) are rare epithelial neoplasms arising in the anterior mediastinum. Platinum-based chemotherapies are widely used for first-line treatment of unresectable IT and TC, but no standard treatment has been established for previously-treated IT and TC thus far. Because promising efficacy of S-1 (tegafur, gimeracil and oteracil combination) has been reported in some retrospective studies, we conducted the first prospective phase II trial to evaluate its efficacy in previously-treated patients with advanced IT and TC. MATERIALS AND METHODS:Patients progressing after at least one regimen of systemic chemotherapy received S-1 orally at a dose based on body surface area for 2 weeks followed by one week of rest until tumor progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profile. We defined an ORR of 25% as indicating potential usefulness while ORR of 10% was the lower limit of interest. RESULTS: Forty patients were enrolled (IT, n = 20; TC, n = 20). ORR was 17.5% (95% CI 7.3-32.8; IT, 10%; TC, 25%), disease control rate was 85% (IT, 95%; TC, 75%). Median PFS was 7.0 months (IT, 11.3 months; TC, 5.4 months), and median OS was 40.3 months (IT, 58.5 months; TC, 22.7 months) with a median follow-up of 51.9 months. Major toxicities (grade 3-4) were anorexia (10%), neutropenia (7.5%) and pneumonitis (5%). No treatment-related death was observed. CONCLUSION: Although the primary endpoint was not met, S-1 monotherapy did have effects similar to recently reported immunotherapies for TC but at much lower cost. S-1 could represent a treatment option for previously-treated advanced TC. This trial was registered as UMIN 000008174.