Treatment with an oral fluoropyrimidine, S-1, plus cisplatin in patients who failed postoperative gemcitabine treatment for pancreatic cancer: a pilot study.
BACKGROUND
This study set out to evaluate, in patients with gemcitabine-resistant pancreatic cancer, the response rate and toxicity of S-1 plus cisplatin (CDDP).


METHODS
Seventeen patients with histologically diagnosed invasive ductal pancreatic cancer were enrolled in this study. All patients had growing recurrent pancreas cancer despite the administration of gemcitabine. Thirteen patients underwent pancreatectomy, and 2 underwent choledochojejunostomy and gastrojejunostomy without pancreatectomy. S-1 (80 mg/m(2) per day) was orally administered for 21 consecutive days, followed by a 14-day rest period. CDDP (40 mg/m(2)) in 500 ml saline was administered by intravenous drip on day 8. This schedule was repeated every 5 weeks until the occurrence of disease progression, unacceptable toxicities, or the patient's refusal to continue.


RESULTS
Five (29.4%) patients achieved a partial response and 2 (11.8%) had stable disease. In 5 of 15 patients (33.3%) who had elevated serum carbohydrate antigen (CA)19-9 levels at the start of treatment the CA19-9 was reduced by more than 50%. The median survival time was 10 months (range, 20 months), with 63.7% and 31.9% of patients alive at 6 and 12 months, respectively. Major adverse reactions in the 15 patients included gastrointestinal toxicities of grade 1 or 2. Only one patient (5.9%) developed grade 3 leucopenia.


CONCLUSIONS
S-1 with CDDP has a promising effect against gemcitabine-resistant pancreatic cancer, with easily manageable toxicities. Further investigation of this regimen is warranted in patients with pancreatic cancer, especially in comparison with gemcitabine.
Togawa
Akira
A
Department of General Surgery, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba, 260-0856, Japan.
Yoshitomi
Hideyuki
H
Ito
Hiroshi
H
Kimura
Fumio
F
Shimizu
Hiroaki
H
Ohtsuka
Masayuki
M
Yoshidome
Hiroyuki
H
Kato
Atsushi
A
Sawada
Shigeaki
S
Miyazaki
Masaru
M
D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D010865:Pilot Projects; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D000093542:Gemcitabine
D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin; D000093542:Gemcitabine
Jpn J Cancer Res. 1987 Jul;78(7):748-55
3114201
Cancer. 2001 Aug 1;92(3):569-77
11505401
Int J Radiat Oncol Biol Phys. 2002 May 1;53(1):140-5
12007952
Oncol Rep. 2002 Nov-Dec;9(6):1355-61
12375048
Anticancer Drugs. 2000 Sep;11(8):623-8
11081453
Cancer. 2002 Feb 15;94(4):902-10
11920457
Ann Surg. 1999 Dec;230(6):776-82; discussion 782-4
10615932
Pancreas. 2003 Oct;27(3):220-4
14508125
Ann Surg. 1990 Apr;211(4):447-58
2322039
Cancer. 1991 Sep 1;68(5):965-9
1833042
Anticancer Drugs. 1996 Jul;7(5):548-57
8862723
Cancer Res. 1996 Jun 1;56(11):2602-6
8653704
Ann Oncol. 2002 Aug;13(8):1185-91
12181240
J Clin Oncol. 1991 Sep;9(9):1682-6
1875224
Ann Oncol. 2002 Oct;13(10):1576-82
12377645
Cancer. 1987 Nov 1;60(9):2284-303
3326653
Am J Surg. 1993 Jan;165(1):68-72; discussion 72-3
8380315
Cancer. 1990 May 15;65(10):2207-12
2189551
Eur J Cancer. 1998 Oct;34(11):1715-20
9893658
Hepatogastroenterology. 2001 May-Jun;48(39):875-8
11462946
J Clin Oncol. 2003 Sep 1;21(17):3296-302
12947065
Clin Cancer Res. 2003 Feb;9(2):555-61
12576418
Pancreas. 2004 Apr;28(3):301-4
15084976
Br J Cancer. 2003 Dec 15;89(12):2207-12
14676796
J Clin Oncol. 2005 May 20;23(15):3509-16
15908661
J Clin Oncol. 2000 Jul;18(14):2772-9
10894878
N Engl J Med. 2004 Mar 18;350(12):1200-10
15028824
Ann Surg. 1995 Jan;221(1):59-66
7826162
J Clin Oncol. 1997 Jun;15(6):2403-13
9196156
Arch Surg. 1985 Aug;120(8):899-903
4015380