Randomized Phase II Trial of S-1 versus S-1 Plus Oxaliplatin (SOX) in Patients with Gemcitabine Refractory Pancreatic Cancer

429 Background: Gemcitabine is one of the standard chemotherapeutic agents for pancreatic cancer in a first-line setting. In a second-line setting, there are various unmet needs. After gemcitabine chemotherapy, S-1 is mainly used and sometimes gemcitabine plus S-1 (GS) is used. Cytotoxic effect of gemcitabine had been reported to have the potential to be enhanced when used with fluorouracil. This randomized study aimed to evaluate the efficacy and safety of gemcitabine plus S-1 in gemcitabine-refractory advanced pancreatic cancer. Methods: This phase II study consisted of patients (pts) who were randomly allocated into the GS group (gemcitabine 1,000 mg/m2 on days 1 and 8 plus S-1 60, 80, or 100 mg/d according to body-surface area on days 1 through 14 of a 21-day cycle) or the S-1 group (S-1 80, 100, or 120 mg/d according to body-surface area on days 1 through 28 of a 42-day cycle) at a 1:1 ratio. The primary endpoint was the evaluation of progression-free survival (PFS). The sample size of 90 pts was chosen based on the randomized phase II selection design reported by Simon et al.(1985). The design suggests a correct selection probability of 75% with two-sided significance level of 0.10 if median PFS is 3.3 mo and 2.0 mo in GS and S-1 groups. Results: From Jan 2012 to March 2015, randomized 51 pts were examined (GS: 26, S-1: 25). This study was discontinued due to slow accrual. The median PFS of GS group was 2.0 mo while the S-1 group was 2.1 mo. The hazard ratio was 1.06 [95%CI 0.60-1.86]; (p=0.844). The median survival times were 3.8 mo in GS group and 5.5 mo in S-1 group, respectively. The hazard ratio was 1.02 [95%CI 0.57-1.81]; (p=0.96). The response rates were 4.2% and 4.3%. The disease control rates were 33.4% and 30.4%. Although bone marrow suppression is higher in GS group, the toxicities were manageable in both groups. Grade 3/4 toxicities (GS/S-1 %) included: neutropenia, 53.8/8; hemoglobin, 30.8/28.0; thrombocytopenia, 7.7/4.0; nausea, 0/8.0; anorexia 11.5/16.0, fatigue 7.7/0 and diarrhea, 3.8/4.0. Conclusions: Gemcitabine plus S-1 is not more effective than S-1 in gemcitabine-refractory advanced pancreatic cancer. Clinical trial information: 000007173.

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A phase I and randomized phase II trial to evaluate the efficacy and safety of nab-paclitaxel (nab-P) in combination with gemcitabine (G) for the treatment of patients with ECOG 2 advanced pancreatic cancer (PDAC)

Annals of Oncology ◽

10.1093/annonc/mdx369.007 ◽

2017 ◽

Vol 28 ◽

pp. v212 ◽

Cited By ~ 2

Author(s):

M. Hidalgo ◽

R. Pazo-Cid ◽

C. Guillen-Ponce ◽

R. López ◽

R. Vera ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase I ◽

Phase Ii ◽

Phase Ii Trial ◽

Advanced Pancreatic Cancer ◽

Efficacy And Safety ◽

Randomized Phase Ii

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A randomized phase II trial of neoadjuvant chemotherapy for patients with resectable pancreatic cancer: Gemcitabine alone vs. gemcitabine combined with cisplatin

Journal of Clinical Oncology ◽

10.1200/jco.2004.22.90140.4215 ◽

2004 ◽

Vol 22 (14_suppl) ◽

pp. 4215-4215

Author(s):

D. H. Palmer ◽

D. D. Stocken ◽

J. A. C. Buckels ◽

H. Hewitt ◽

C. E. Markham ◽

...

Keyword(s):

Pancreatic Cancer ◽

Neoadjuvant Chemotherapy ◽

Phase Ii ◽

Phase Ii Trial ◽

Resectable Pancreatic Cancer ◽

Randomized Phase Ii

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Randomized phase II trial of S-1 versus S-1 plus irinotecan (IRIS) in patients with gemcitabine-refractory pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.263 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 263-263 ◽

Cited By ~ 7

Author(s):

Nobumasa Mizuno ◽

Kenji Yamao ◽

Yoshito Komatsu ◽

Masaki Munakata ◽

Atsushi Ishiguro ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase Ii ◽

Phase Ii Trial ◽

Advanced Pancreatic Cancer ◽

Progression Free Survival ◽

Metastatic Lesion ◽

Second Line ◽

First Line Therapy ◽

Line Therapy ◽

Randomized Phase Ii

263 Background: Gemcitabine (Gem) monotherapy or Gem-based combination therapy is a standard first-line therapy for advanced pancreatic cancer (PC). There is no consensus on second-line therapy in patients (pts) with disease progression (PD) after Gem-based therapy. S-1, an oral fluoropyrimidine derivative, is commonly used for the second-line treatment of PC in Japan. Shitara et al previously reported that IRIS regimen showed that 44% of response rate (RR), 4.9 mo of median progression free survival (PFS), and 11.3 mo of median overall survival (OS), respectively. Therefore a randomized phase II trial was conducted to evaluate the efficacy and safety of IRIS compared with S-1 alone in the second-line setting. Methods: The inclusion criteria were as follows: (1) histologically or cytologically proven pancreatic adenocarcinoma or adenosquamous carcinoma; (2) confirmed PD after Gem treatment; (3) ECOG PS, 0-1; (4) measurable metastatic lesion based on RECIST criteria; (5) age ≥ 20 years; (6) total bilirubin < 2.0 mg/dL. Patients were randomized to receive either IRIS (CPT-11 100 mg/m2, iv, d1,15 plus S-1 80/100/120 mg/day based on BSA, po, d1-14, q4w; Arm A) or S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w; Arm B). The primary endpoint was to compare PFS in Arm A and Arm B. Results: Of a total of 137 pts enrolled between Nov 2008 and Mar 2011, 127 were eligible (60 randomized to Arm A and 67 to B). Median PFS in Arm A and B was 107 and 58 days, respectively (HR= 0.767; 95% CI, 0.527-1.114; p=0.1750). Median OS in Arm A and B was 208 and 176 days, respectively (HR=0.749; 95% CI, 0.512-1.093; p=0.1338). RR was 18.3% in Arm A (11/60; 95% CI, 9.5-30.4) and 6.0% in Arm B (4/67; 95% CI, 1.7-14.6)(p=0.0311). The incidences of grade 3/4 toxicities were as follows: neutropenia (15.6% and 4.3%), anorexia (23.4% and 17.3%), nausea (6.3% and 2.9%), and diarrhea (3.1% and 2.9%) in Arm A and B, respectively. Both regimens were tolerable. Conclusions: Although IRIS showed no significant improvement in PFS or OS compared with S-1 alone in this study, it showed significant advantage in RR, and favorable HR in both of PFS and OS. IRIS might have potential power to treat second-line PC patients. Further study is warranted. Clinical trial information: JapicCTI-080657.

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