A phase 2 randomized study of TAS-102 versus topotecan or amrubicin in patients requiring second-line chemotherapy for small cell lung cancer refractory or sensitive to frontline platinum-based chemotherapy.
TAS-102 is an oral combination treatment comprised of an antimetabolite, trifluridine, a thymidine-based nucleoside analog, and tipiracil hydrochloride, at a molar ratio of 1:0.5. This antimetabolite has demonstrated efficacy in clinical trials, including a global phase 3 trial in metastatic colorectal cancer. As this agent has shown activity greater than cisplatin in small cell lung cancer xenograft mouse models, the objective of this study was to evaluate TAS-102 in the second-line treatment of small cell lung cancer.



This was a multicenter, open-label, two-arm, randomized phase 2 study designed to compare oral TAS-102 (35mg/m(2)/dose twice daily) versus control (topotecan or amrubicin). Patients requiring second-line chemotherapy for treatment of small cell lung cancer, either refractory or sensitive to frontline platinum-based chemotherapy, were enrolled.



Eighteen patients were enrolled. Eight of nine patients receiving TAS-102 discontinued treatment due to progressive disease and one patient died due to clinical progression during the safety follow-up. Unplanned interim futility considerations were made, and the study was terminated early because it was unlikely that superiority of TAS-102 versus comparator could be demonstrated. Six control patients discontinued therapy due to progressive disease and one due to an adverse event. Median progression-free survival was 1.4 months (range 0.9-1.8) versus 2.7 months (range 1.0-6.8) for TAS-102 and control, respectively, with a hazard ratio of 3.76 (80% CI, 1.68-8.40) favoring control. The most common adverse events with TAS-102 were neutropenia, diarrhea, anemia, anorexia, and fatigue, each in three patients.



TAS-102 showed no evidence of activity in second-line small cell lung cancer.
University of Torino, Department of Oncology at S. Luigi Hospital, Orbassano, Italy. Electronic address: giorgio.scagliotti@unito.it.
Giorgio
G
Scagliotti
Cancer Institute Hospital of The Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
Makoto
M
Nishio
Hyogo Cancer Center, Akashi, Hyogo, Japan.
Miyako
M
Satouchi
A.O.V.V. Ospedale Eugenio Morelli-Sondalo, Sondalo, Italy.
Giuseppe
G
Valmadre
National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Seiji
S
Niho
Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari, Bari, Italy.
Domenico
D
Galetta
Azienda Ospedaliera San Gerardo, Monza, Italy.
Diego
D
Cortinovis
Taiho Oncology, Inc., Princeton, NJ, USA.
Fabio
F
Benedetti
Taiho Pharmaceutical Co. Ltd., Chiyoda-ku, Tokyo, Japan.
Eiji
E
Yoshihara
Stathmi Inc., New Hope, PA, USA.
Lukas
L
Makris
Tohoku University School of Medicine, Sendai, Miyagi, Japan.
Akira
A
Inoue
Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
Kaoru
K
Kubota
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010984:Platinum / Q000627:therapeutic use*; D011759:Pyrrolidines; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy; D013941:Thymine; D019772:Topotecan / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D014271:Trifluridine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D018943:Anthracyclines; D000970:Antineoplastic Agents; D004338:Drug Combinations; D011759:Pyrrolidines; C000613803:trifluridine tipiracil drug combination; D010984:Platinum; D014498:Uracil; D019772:Topotecan; C055866:amrubicin; D013941:Thymine; D014271:Trifluridine
Amrubicin; Randomized trial; Small cell lung cancer; TAS-102; Topotecan