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2221 Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer; short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG 0501)
S406 (85%) and chills (62%) and some patients also experienced headache (25%) and gastro-intestinal symptoms (anorexia [38%], nausea [36%], vomiting [27%]). Transient hypotension was also observed (25%). PexaVec-containing pustules (Grade 1) were observed in 6% of patients treated with IT 109 pfu. Adverse event incidence and severity appeared to decrease with repeated administration of Pexa-Vec. One procedurerelated hemorrhage and sepsis event was recorded. 18% of patients experienced injection site pain. No procedure-related deaths were reported. Intra-tumoral injections of Pexa-Vec were demonstrated to be feasible, safe and effective in patients with hepatocellular carcinoma. Physicians routinely performing locoregional treatments of liver tumors were able to rapidly learn the Pexa-Vec injection technique. Conclusions: Treatment with IT Pexa-Vec of patients with liver tumors was generally well-tolerated with few instances of procedure-related adverse events. In HCC, administration procedure and patient management after IT Pexa-Vec compares favorably with RFA, TACE and SIRT. A Phase 3 trial involving 3 IT Pexa-Vec treatments in combination with sorafenib versus sorafenib alone in sorafenib-na¨ıve patients is planned. Conflict of interest: Other Substantive Relationships: Riccardo Lencioni and David H. Kirn consult for Sillajen Inc. Caroline J. Breitbach and James M. Burke are Sillajen Inc. employees. Michel Homerin, Monika Lusky and Nicolas Stojkowitz areTransgene S.A. employees. 2220 POSTER Neoadjuvant chemoradiotherapy with cisplatin plus vinorelbine versus cisplatin plus fluorouracil for esophageal squamous cell carcinoma M. Xi1 , L. Zhang1 , S.L. Liu1 , M.Z. Liu1 , H. Yang2 . 1 Sun Yat-sen University Cancer Center, Radiation Oncology, Guangzhou City, China; 2 Sun Yat-sen University Cancer Center, Thoracic Oncology, Guangzhou City, China Background: To compare the clinical outcomes of neoadjuvant chemoradiotherapy (CRT) with cisplatin/vinorelbine versus cisplatin/fluorouracil in patients with locally advanced esophageal cancer. Material and Methods: Between 2000 and 2012, 279 patients with thoracic esophageal squamous cell carcinoma (SCC) undergoing neoadjuvant CRT followed by surgery were reviewed. Through a matched case–control study, 57 patients treated with cisplatin/vinorelbine were matched 1:1 to patients who received cisplatin/fluorouracil according to age, sex, performance status, tumor location, tumor length, and pretreatment TNM stage. Results: Patient and disease-related characteristics were comparable between the two groups. The pathologic complete response (pCR) rate was 47.4% for the cisplatin/vinorelbine group and 28.1% for the cisplatin/fluorouracil group (P = 0.034). Median overall survival (OS) in the cisplatin/vinorelbine group was significantly better compared with the cisplatin/fluorouracil group (52.8 vs. 25.2 months), with 3-year OS rates of 64.3% vs. 31.3%, respectively (P = 0.001). However, cisplatin/ vinorelbine was associated with a significantly higher rate of grade 3−4 leukopenia than cisplatin/fluorouracil (P = 0.03). Occurrence of surgical complications was not significantly different between the two groups. Multivariate analysis showed that being female, age 55 years, pCR after CRT, and chemotherapy with cisplatin/vinorelbine were independent positive prognostic factors for survival. Conclusions: Cisplatin/vinorelbine leads to a significantly higher pCR rate and better survival than cisplatin/fluorouracil in patients with esophageal SCC. The incidence of hematologic toxicity is increased with cisplatin/ vinorelbine, but is tolerable and manageable. No conflict of interest.
Abstracts 2221 POSTER Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer; short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG 0501) M. Terashima1 , Y. Iwasaki2 , J. Mizusawa3 , H. Katayama3 , K. Nakamura3 , H. Katai4 , T. Yoshikawa5 , S. Ito6 , M. Kaji7 , Y. Kimura8 , M. Hirao9 , M. Yamada10 , A. Kurita11 , M. Takagi12 , M. Goto13 , A. Takagane14 , H. Yabuzaki15 , N. Hirabayashi16 , T. Sano17 , M. Sasako18 . 1 Shizuoka Cancer Center, Division of Gastric Surgery, Sunto-gun, Japan; 2 Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Department of Gastric Surgery, Tokyo, Japan; 3 National Cancer Center, JCOG Data Center/Operations Office, Center for Research Administration and Support, Tokyo, Japan; 4 Gastric Cancer Division, National Cancer Center Hospital, Tokyo, Japan; 5 Department of Gastrointestinal Suergery, Kanagawa Cancer Center, Yokohama, Japan; 6 Aichi Cancer Center-, Department of Gastroenterological Surgery, Nagoya, Japan; 7 Toyama Prefectural Central Hospital, Department of Surgery, Toyama, Japan; 8 Sakai City Hospital, Department of Surgery, Sakai, Japan; 9 National Hospital Organization Osaka National Hospital, Department of Surgery, Osaka, Japan; 10 Gifu Municipal Hospital, Department of Surgery, Gifu, Japan; 11 National Hospital Organization Shikoku Cancer Center, Department of Surgery, Matsuyama, Japan; 12 Shizuoka General Hospital, Department of Surgery, Shizuoka, Japan; 13 Osaka Medical College, Cancer Chemotherapy Center, Osaka, Japan; 14 Hakodate Goryoukaku Hospital, Department of Surgery, Hakodate, Japan; 15 Niigata Cancer Center Hospital, Department of Surgery, Niigata, Japan; 16 Hiroshima City Asa Hospital, Department of Surgery, Hiroshima, Japan; 17 Cancer Institute Hospital, Gastrointestinal Surgery, Tokyo, Japan; 18 Hyogo College of Medicine, Department of Surgery, Nishinomiya, Japan Background: The prognosis of patients with linitis plastica (type 4) and large (8 cm) ulcero-invasive-type (type 3) are extremely poor even after extended surgery and adjuvant chemotherapy. Based on the promising results in our previous phase II study evaluating neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (CDDP), we proceeded to phase III study to confirm the efficacy of NAC in these subtypes of patients. Material and Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; clinically resectable gastric cancer of type 4 or large type 3. Staging laparoscopy was mandatory. Patients were randomized to NAC (S-1, 80–120 mg/body, days 1−21 and cisplatin, 60 mg/m2 , day 8, q28, 2courses) followed by gastrectomy + adjuvant chemotherapy (S-1, days 1−28, q42 days for 1 year) (PERI) or gastrectomy plus adjuvant chemotherapy with S-1 (POST). Primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival, response rate, R0 resection rate and adverse event (AE). A total of 300 patients were required to detect 10% difference in 3-year OS with a onesided 5% significance level and 80% power. Protocol was revised to include patients with localized peritoneal metastasis or positive peritoneal cytology in the midst of the accrual period due to slow accrual. Results: Between Feb 2007 and Jul 2013, 300 patients were accrued (PERI 151, POST 149). There was no significant difference of patients’ background. NAC was completed in 133 patients (88%). The reasons for termination of NAC were tumor progression in 2, AEs related in 12, patient refusal in 1 and others in 3. During NAC, grade 4 gastric perforation was observed in 1 and grade 4 hyponatremia in 2. Grade 3 non-hematological AE except for laboratory data was observed in 30/147(19.7%). Major grade 3/4 AEs during NAC were neutropenia (29.3%), nausea (5.4%), diarrhea (4.8%), and fatigue (2.7%). One patient revealed infection with neutropenia. Gastrectomy was performed in 147 patients (99%) in POST and 139 patients (92%) in PERI. R0 resection was possible in 98 patients (66%) in POST and 112 patients (74%) in PERI. The blood loss was relatively smaller in PERI (median; 420 ml in POST vs 330 ml in PERI). The operation time was slightly shorter in PERI. There were no remarkable differences in morbidity between the groups. Two patients in POST died due to acute bacterial enteritis and strangulated ileus, and 1 patient in PERI due to strangulated ileus. The 3-year and 5-year overall survival as a whole were 61% and 47%, respectively. Conclusions: NAC for type 4 and large type 3 gastric cancer followed by D2 gastrectomy can be safely performed without increasing morbidity and mortality. Linitis plastica remains surgical disease with appropriate adjuvant treatment. Final survival result will be demonstrated in 2017. UMIN-C000000279 No conflict of interest.
Abstracts 2221 POSTER Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer; short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG 0501) M. Terashima1 , Y. Iwasaki2 , J. Mizusawa3 , H. Katayama3 , K. Nakamura3 , H. Katai4 , T. Yoshikawa5 , S. Ito6 , M. Kaji7 , Y. Kimura8 , M. Hirao9 , M. Yamada10 , A. Kurita11 , M. Takagi12 , M. Goto13 , A. Takagane14 , H. Yabuzaki15 , N. Hirabayashi16 , T. Sano17 , M. Sasako18 . 1 Shizuoka Cancer Center, Division of Gastric Surgery, Sunto-gun, Japan; 2 Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Department of Gastric Surgery, Tokyo, Japan; 3 National Cancer Center, JCOG Data Center/Operations Office, Center for Research Administration and Support, Tokyo, Japan; 4 Gastric Cancer Division, National Cancer Center Hospital, Tokyo, Japan; 5 Department of Gastrointestinal Suergery, Kanagawa Cancer Center, Yokohama, Japan; 6 Aichi Cancer Center-, Department of Gastroenterological Surgery, Nagoya, Japan; 7 Toyama Prefectural Central Hospital, Department of Surgery, Toyama, Japan; 8 Sakai City Hospital, Department of Surgery, Sakai, Japan; 9 National Hospital Organization Osaka National Hospital, Department of Surgery, Osaka, Japan; 10 Gifu Municipal Hospital, Department of Surgery, Gifu, Japan; 11 National Hospital Organization Shikoku Cancer Center, Department of Surgery, Matsuyama, Japan; 12 Shizuoka General Hospital, Department of Surgery, Shizuoka, Japan; 13 Osaka Medical College, Cancer Chemotherapy Center, Osaka, Japan; 14 Hakodate Goryoukaku Hospital, Department of Surgery, Hakodate, Japan; 15 Niigata Cancer Center Hospital, Department of Surgery, Niigata, Japan; 16 Hiroshima City Asa Hospital, Department of Surgery, Hiroshima, Japan; 17 Cancer Institute Hospital, Gastrointestinal Surgery, Tokyo, Japan; 18 Hyogo College of Medicine, Department of Surgery, Nishinomiya, Japan Background: The prognosis of patients with linitis plastica (type 4) and large (8 cm) ulcero-invasive-type (type 3) are extremely poor even after extended surgery and adjuvant chemotherapy. Based on the promising results in our previous phase II study evaluating neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (CDDP), we proceeded to phase III study to confirm the efficacy of NAC in these subtypes of patients. Material and Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; clinically resectable gastric cancer of type 4 or large type 3. Staging laparoscopy was mandatory. Patients were randomized to NAC (S-1, 80–120 mg/body, days 1−21 and cisplatin, 60 mg/m2 , day 8, q28, 2courses) followed by gastrectomy + adjuvant chemotherapy (S-1, days 1−28, q42 days for 1 year) (PERI) or gastrectomy plus adjuvant chemotherapy with S-1 (POST). Primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival, response rate, R0 resection rate and adverse event (AE). A total of 300 patients were required to detect 10% difference in 3-year OS with a onesided 5% significance level and 80% power. Protocol was revised to include patients with localized peritoneal metastasis or positive peritoneal cytology in the midst of the accrual period due to slow accrual. Results: Between Feb 2007 and Jul 2013, 300 patients were accrued (PERI 151, POST 149). There was no significant difference of patients’ background. NAC was completed in 133 patients (88%). The reasons for termination of NAC were tumor progression in 2, AEs related in 12, patient refusal in 1 and others in 3. During NAC, grade 4 gastric perforation was observed in 1 and grade 4 hyponatremia in 2. Grade 3 non-hematological AE except for laboratory data was observed in 30/147(19.7%). Major grade 3/4 AEs during NAC were neutropenia (29.3%), nausea (5.4%), diarrhea (4.8%), and fatigue (2.7%). One patient revealed infection with neutropenia. Gastrectomy was performed in 147 patients (99%) in POST and 139 patients (92%) in PERI. R0 resection was possible in 98 patients (66%) in POST and 112 patients (74%) in PERI. The blood loss was relatively smaller in PERI (median; 420 ml in POST vs 330 ml in PERI). The operation time was slightly shorter in PERI. There were no remarkable differences in morbidity between the groups. Two patients in POST died due to acute bacterial enteritis and strangulated ileus, and 1 patient in PERI due to strangulated ileus. The 3-year and 5-year overall survival as a whole were 61% and 47%, respectively. Conclusions: NAC for type 4 and large type 3 gastric cancer followed by D2 gastrectomy can be safely performed without increasing morbidity and mortality. Linitis plastica remains surgical disease with appropriate adjuvant treatment. Final survival result will be demonstrated in 2017. UMIN-C000000279 No conflict of interest.