A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer.
OBJECTIVE
Curcumin, a plant-derived natural polyphenol, could be a promising anti-cancer drug and shows synergic effects with cytotoxic agents. We evaluated the safety and feasibility of combination therapy using curcumin with gemcitabine-based chemotherapy.


METHODS
Gemcitabine-resistant patients with pancreatic cancer received 8 g oral curcumin daily in combination with gemcitabine-based chemotherapy. The primary endpoint was safety for phase I and feasibility of oral curcumin for phase II study.


RESULTS
Twenty-one patients were enrolled. No dose-limiting toxicities were observed in the phase I study and oral curcumin 8 g/day was selected as the recommended dose for the phase II study. No patients were withdrawn from this study because of the intolerability of curcumin, which met the primary endpoint of the phase II study, and the median compliance rate of oral curcumin was 100% (Range 79-100%). Median survival time after initiation of curcumin was 161 days (95% confidence interval 109-223 days) and 1-year survival rate was 19% (4.4-41.4%). Plasma curcumin levels ranged from 29 to 412 ng/ml in five patients tested.


CONCLUSIONS
Combination therapy using 8 g oral curcumin daily with gemcitabine-based chemotherapy was safe and feasible in patients with pancreatic cancer and warrants further investigation into its efficacy.
Kanai
Masashi
M
Outpatient Oncology Unit, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. kanai@kuhp.kyoto-u.ac.jp
Yoshimura
Kenichi
K
Asada
Masanori
M
Imaizumi
Atsushi
A
Suzuki
Chihiro
C
Matsumoto
Shigemi
S
Nishimura
Takafumi
T
Mori
Yukiko
Y
Masui
Toshihiko
T
Kawaguchi
Yoshiya
Y
Yanagihara
Kazuhiro
K
Yazumi
Shujiro
S
Chiba
Tsutomu
T
Guha
Sushovan
S
Aggarwal
Bharat B
BB
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003474:Curcumin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010094:Oxonic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015996:Survival Rate; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D003474:Curcumin; D000093542:Gemcitabine