Retrospective analysis of S-1 monotherapy in patients with metastatic colorectal cancer after failure to fluoropyrimidine and irinotecan or to fluoropyrimidine, irinotecan and oxaliplatin.
OBJECTIVE
Chemotherapy with irinotecan (CPT-11) or oxaliplatin (l-OHP) in combination with infusional 5-fluorouracil (5-FU) and their cross-over as second-line therapies are standard treatments for metastatic colorectal cancer (MCRC). Molecular target agents, which are used as third-line therapies in Western countries after failure of these three drugs, have not been available in Japan. Monotherapy with S-1 [Tegafur, Oteracil potassium and 5-chloro-2,4-dihydroxypyrimidine (CDHP)] showed activity against colorectal cancer with a response rate of 35% as a first-line therapy. It is not clear whether inhibition of dihydropyrimidine dehydrogenase by CDHP can modulate the activity of 5-FU even after patients initially fail with 5-FU. This retrospective study evaluated the efficacy and safety of monotherapy with S-1 for MCRC after the failure of standard chemotherapy.


METHODS
The subjects of this study comprised two cohorts; the first was 27 patients with MCRC who had failed with 5-FU and CPT-11 before approval of l-OHP in Japan (cohort 1), and the second was 23 patients who had failed with 5-FU, CPT-11 and l-OHP (cohort 2). S-1 was given orally twice daily (80 mg m(2)/day) for 28 days followed by a 14-day rest.


RESULTS
In cohorts 1 and 2, the response rates were 7% and 0%, and the median progression-free survivals were 2.8 and 2.7 months, and overall survivals after initiation of S-1 were 10.5 and 4.7 months, respectively. The common grade 3 and 4 adverse events in cohorts 1 and 2 were diarrhea 15% and 13%, anorexia 11% and 17% and anemia 26% and 30%, respectively.


CONCLUSIONS
S-1 monotherapy did not show promising activity against MCRC after the failures with 5-FU, CPT-11 and l-OHP.
Yasui
Hirofumi
H
Division of GI Oncology, Shizuoka Cancer Center, Sunto-Gun, Shizuoka, Japan. h.yasui@scchr.jp
Yoshino
Takayuki
T
Boku
Narikazu
N
Onozawa
Yusuke
Y
Hironaka
Shuichi
S
Fukutomi
Akira
A
Yamazaki
Kentaro
K
Taku
Keisei
K
Kojima
Takashi
T
Machida
Nozomu
N
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage; D012189:Retrospective Studies; D005641:Tegafur / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D009944:Organoplatinum Compounds; D011743:Pyrimidines; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin