Yoshihiro Okita

18F-fluorodeoxyglucose positron emission tomography to indicate conversion surgery in patients with initially unresectable locally advanced pancreatic cancer

Objective Advances in chemotherapy and chemoradiotherapy have enabled conversion of initially unresectable locally advanced (UR-LA) pancreatic adenocarcinoma (PDAC) to a resectable disease. However, definitive criteria for conversion surgery have not been established. We evaluated the potential of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to indicate conversion surgery in patients with primary UR-LA PDAC. Methods Twenty consecutive patients with UR-LA PDAC underwent chemoradiation or chemotherapy followed by assessment with FDG-PET. We defined PET responders (standardized uptake value <3.0) with marked reduction (>80%) of carbohydrate antigen 19-9 as potential candidates for conversion surgery. Outcomes were compared with those of the patients with resectable (R; n = 94) and borderline resectable (BR; n = 37) PDAC. Results Eight of the 20 patients (40%) were considered PET responders with marked reduction of CA19-9 and received conversion surgery (UR-LAR) 3-9 months (median, 5 months) after the initiation of therapy. Complete resection (R0) was achieved in 7 of 8 patients (87.5%) with UR-LAR. There was no significant difference in R0 rates, morbidity, or mortality among the UR-LAR, R and BR groups. The overall survival (OS) curve was better in the UR-LAR group than in the group that did not receive surgery. There was no significant difference in OS between the UR-LAR and the R or BR groups. Conclusions FDG-PET could be a potential indicator for conversion surgery in patients with primary UR-LA PDAC and may help in selecting patients who qualify for complete surgical resection and have a promising prognosis.

Prevalence and risk factors of hepatitis B virus reactivation in patients with solid tumors with resolved HBV infection

Reports of hepatitis B virus (HBV) reactivation in solid tumors are very limited, and their frequencies and risk factors were previously unknown.

First‑line chemotherapy with capecitabine/oxaliplatin for advanced gastric cancer: A phase I study

Combination chemotherapy with capecitabine and oxaliplatin for gastric cancer (G-XELOX) is considered as a potentially promising regimen. However, the use of the G-XELOX regimen in Japanese patients has not been investigated to date, and recommended doses of G-XELOX for Japanese patients with metastatic gastric cancer have not been established. The aim of the present study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) for systemic chemotherapy with G-XELOX for metastatic gastric cancer. The enrolled patients received systemic chemotherapy with oxaliplatin 130 mg/m2 on day 1 and capecitabine 2,000 mg/m2/day, b.i.d. for 14 days, repeated every 3 weeks. A decrease in oxaliplatin dose was planned from start level 1 (130 mg/m2). A total of 6 patients were enrolled between January and July 2015. MTD was not reached at level 1. Oxaliplatin 130 mg/m2 in combination with capecitabine 2,000 mg/m2/day b.i.d. could be administered with acceptable toxicity, and all patients were treated at these doses. One case of grade 3 stomatitis was considered as a dose-limiting toxicity at level 1; however, excluding this case, no grade 3 or 4 non-hematological toxicity was observed. There were no treatment-related deaths. The median relative dose intensity was 71.3% for capecitabine and 92.1% for oxaliplatin. Of the 6 patients, 3 had measurable lesions according to the Response Evaluation Criteria In Solid Tumors; the response rate and disease control rate were both 67%. Therefore, systemic chemotherapy with G-XELOX was well-tolerated by patients with advanced gastric cancer. The RD was defined as oxaliplatin 130 mg/m2 in combination with capecitabine 2,000 mg/m2/day b.i.d.

Phase I study of neoadjuvant chemotherapy with S-1 and oxaliplatin for locally advanced gastric cancer (Neo G-SOX PI)

Background The prognosis of locally advanced gastric cancer, such as clinical T4 disease, bulky nodal involvement, type 4 and large type 3 gastric cancer, remains unsatisfactory, even with D2 gastrectomy followed by adjuvant chemotherapy. One promising approach is neoadjuvant chemotherapy. Combination chemotherapy with S-1 and oxaliplatin (SOX) is recognised as a potentially promising regimen for gastric cancer. However, the use of neoadjuvant chemotherapy consisting of SOX for locally advanced gastric cancer has not been reported. The aim of this study was to determine the maximum tolerated dose (MTD) and recommended dose of preoperative chemotherapy combined with SOX for locally advanced gastric cancer. Methods Patients received two cycles of neoadjuvant chemotherapy with oxaliplatin on day 1, as well as S-1 (80 mg/m2/day, twice daily) for 14 days, repeated every 3 weeks. They then underwent gastrectomy with curative D2/3 lymph node dissection followed by adjuvant S-1 (80 mg/m2/day, twice daily) for 1 year. Escalation of oxaliplatin dose was planned (starting at level 0, oxaliplatin 100 mg/m2; level 1, 130 mg/m2). Results Six patients were enrolled. MTD was not reached at level 1. Oxaliplatin 130 mg/m2 in combination with S-1 80 mg/m2/day twice daily could be administered with acceptable toxicity. Peripheral neuropathy was observed in all patients but with no functional disorders. No treatment-related death was observed and the incidence of operative morbidity was tolerable. Resection with curative intent was undertaken in all patients with R0 resection performed in five (83%) and R1 in one. Two of the six patients had a pathological complete response (33%). Conclusion Neoadjuvant chemotherapy with an SOX regimen was feasible in patients with locally advanced gastric cancer. The recommended phase II dose was determined to be oxaliplatin 130 mg/m2 in combination with S-1 80 mg/m2/day, twice daily.

P1-104Feasibility study of FOLFIRINOX as first-line chemotherapy for metastatic pancreatic cancer (KOBE FOLFIRINOX study)

Results: RAS mutations testing of 32 mCRC pts were 15 RAS wild-type(wt) and 17 RAS mutant type(mt) (KRAS exon2 mt: other RAS mt 11:6). The proportion of Rigt side tumor location(cecumtransverse colon) was more in RAS mt(35.3%) than in RAS wt(20.0%).Medical condition of 32 pts was ’fit’condition of 27 pts (RAS wt:mt 14:13) and ’may be unfit’condition of 5 pts (RAS wt:mt 1:4) .Among 14 RAS wt and ’fit’condition pts, 7 pts who assign treatment goal to Cytoreduction were chosen Chemothrapy (CT) doublet plus anti-EGFR and 7 pts who assign treatment goal to Disease control were chosen CT doublet plus Bevacizumab(Bmab) as first-line CT. 13 RAS mt and ’fit’condition pts were all chosen CT doublet plus Bmab as first-line CT. Among 5 ’may be unfit’condition pts, 3 pts were chosen reduced CT doublet, 1 pts fluoropyrmidine(FP)þBmab and 1 pts FP as first-line CT. Regarding first Response Rate evaluation of First-line CT(except discontinued and not evaluated pts), RAS wt and ’fit’condition group was 66.7%, RAS mt and ’fit’condition group was 44.4%,and ’may be unfit’condition group was 25.0%. By undergoing first-lineCT, 4 ’fit’condition pts who assign treatment goal to Cytoreduction became possible for Conversion surgery(RAS wt:mt 3:1).

Multicenter phase II study of neoadjuvant chemotherapy consisted with S-1 and oxaliplatin followed by gastrectomy for locally advanced gastric cancer.

TPS180 Background: Prognosis for locally advanced gastric cancer, such as clinical T4 disease, bulky nodal involvement, type 4 and large type 3 gastric cancer, was not satisfactory even by D2 gastrectomy followed by adjuvant chemotherapy. Neoadjuvant chemotherapy is another promising approach. In our phase I study, neoadjuvant chemotherapy of S-1 and oxaliplatin (SOX) had manageable toxicities and good pathological complete response rate (33%) in patients with locally advanced gastric cancer. Based on the results of this phase I study, we initiate a multi-institutional, single-arm, open label, phase II study (Neo G-SOX PII study). The aim of this study is to evaluate the efficacy and safety of the neoadjuvant chemotherapy of S-1 and oxaliplatin (SOX) followed by gastrectomy with D2/3 lymph node dissection; clinical T4; clinically resectable gastric cancer of type 4 or large type 3 (over 8 cm); bulky nodal involvement around major branched arteries to the stomach Methods: Eligibility criteria include histol...