A phase II study of preoperative chemotherapy (CX) with S-1 and cisplatin followed by gastrectomy for clinically resectable type 4 and large type 3 gastric cancer: JCOG 0210

<jats:p> 4609 </jats:p><jats:p> Background: Prognosis of both linitis plastica (type 4) and large ulcero-invasive type (type 3) gastric cancer is poor even after curative resection. We conducted a phase II study to evaluate the safety and efficacy of preoperative CX with S-1 and cisplatin followed by gastrectomy in patients (pts) with these tumors. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; clinically resectable gastric cancer of type 4 or type 3 of =8 cm; cN0–2; cM0; PS 0–1; 20–75 years old. Pts received two 28-day cycles of induction CX of S-1 (80–120 mg/body, po, day 1–21) and cisplatin (60mg/m<jats:sup>2</jats:sup>, iv, day 8). Gastrectomy with D2/3 dissection was performed within 3 to 5 weeks after CX. No adjuvant therapy was added until recurrence after the curative gastrectomy. Primary endpoints were the proportion of protocol achievement and incidence of treatment related death (TRD). Sample size was determined to reject the rate of 45% under the expectation of 60% with power of 80% and alpha of 10%. Results: Fifty pts, 29 males and 21 females with a median age of 61 years (range: 32–75), were entered in this study between 03/2003 and 12/2003. Type 3/4 ratio was 20/30. Surgical exploration was carried out in 48 pts (96%). Among 49 eligible pts, 36 pts (73%; 95% CI, 59–85%) received two cycles of induction CX and R0 resection. One TRD was observed during the first course of CX due to uncontrollable hemorrhage from the primary tumor. Median survival time and the 3- year OS were 1.44 years (95% CI, 1.26–1.98) and 26.0% (95% CI, 14.9–38.6%), respectively. Pathological response, defined as disappearance of more than one third of the primary tumor, was confirmed in 24 pts (48%) and pathological complete response was seen in 1 pts (2%). During the CX, grade 3/4 neutropenia and anorexia occurred in 7 pts (14%), respectively. Postoperative morbidity included pneumonia in 2 pts, pancreatic leakage in 4, and intraperitoneal abscess in 3, without any mortality. Conclusions: Preoperative CX with S-1 and cisplatin followed by gastrectomy was safe and promising for type 4 and large type 3 gastric cancer. The results of ongoing phase III study to evaluate this treatment are awaited. </jats:p><jats:p> No significant financial relationships to disclose. </jats:p>