Randomised phase II trial of photodynamic therapy plus oral fluoropyrimidine, S-1, versus photodynamic therapy alone for unresectable hilar cholangiocarcinoma.
BACKGROUND
Hilar cholangiocarcinoma is an uncommon cancer and its overall incidence is increasing. Photodynamic therapy (PDT) has been proposed as palliative management for unresectable hilar cholangiocarcinoma (UHC). To date, little is known about the role of the addition of systemic chemotherapy to PDT for UHC. We performed a prospective, randomised, phase II trial to compare PDT plus S-1 and PDT alone for UHC.


METHODS
Patients with UHC were randomly assigned (in a 1:1 ratio) to PDT plus S-1 or PDT alone. The primary end-point was overall survival. The secondary end-points were progression-free survival, complications, re-intervention rate and quality of life. This trial is registered with clinicalTrials.gov, number NCT00869635.


RESULTS
Between February 2009 and May 2012, we randomly assigned 21 patients to receive PDT plus S-1 and 22 to receive PDT alone. The UHC patients treated with PDT plus S-1 showed higher 1-year survival rate compared with the patients treated with PDT alone (76.2% versus 32%, P=0.003) and prolonged overall survival (median 17 months, 95% confidence interval [CI]: 12.6-21.4, versus 8 months, 95% CI: 6-10, P=0.005, hazard ratio [HR], 0.36; 95% CI: 0.17-0.75). Regarding the secondary end-points, PDT plus S-1 was associated with prolonged progression-free survival compared with PDT alone (median 10 months [95% CI: 4.1-16] versus 2 months [95% CI: 0.4-3.5], P=0.009 (HR for progression 0.39, 95% CI: 0.19-0.83). There were no differences in the number of PDT sessions, the frequency of cholangitis, overall adverse events or the quality of life in either group.


CONCLUSIONS
PDT plus S-1 was well tolerated and was associated with a significant improvement of overall survival and progression-free survival compared with PDT alone in patients with UHC. These findings warrant further clinical investigation of PDT plus S-1 in patients with UHC.
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea. Electronic address: dhpark@amc.seoul.kr.
Do Hyun
DH
Park
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
Sang Soo
SS
Lee
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
So Eun
SE
Park
Division of Oncology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
Jae Lyun
JL
Lee
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
Jun Ho
JH
Choi
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
Hee Jung
HJ
Choi
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
Ji Woong
JW
Jang
Department of Radiology, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
Hyoung Jung
HJ
Kim
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
Jun Bum
JB
Eum
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
Dong-Wan
DW
Seo
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
Sung Koo
SK
Lee
Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
Myung-Hwan
MH
Kim
Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.
Jung Bok
JB
Lee
D000284:Administration, Oral; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000401:mortality; D003131:Combined Modality Therapy / Q000379:methods; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D010778:Photochemotherapy / Q000379:methods*; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage; D011788:Quality of Life; D019233:Retreatment / Q000706:statistics & numerical data; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage; D014481:United States / Q000453:epidemiology
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004338:Drug Combinations; D011743:Pyrimidines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; C030986:pyrimidine
Cholangiocarcinoma; Overall survival; Photodynamic therapy; Randomised trial; S-1