Ott Katja, Sendler Andreas, Becker Karen, Dittler Hans-Joachim, Helmberger Hermann, Busch Raimonde, Kollmannsberger Christian, Siewert J Rüdiger, Fink Ulrich
Department of Surgery, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 Munich, Germany.
Gastric Cancer. 2003;6(3):159-67. doi: 10.1007/s10120-003-0245-4.
Patients with locally advanced gastric cancer (cT3, cT4, N+, M0) have a dismal prognosis, despite complete resection. The objective of this study was to evaluate the toxicity and efficacy of neoadjuvant chemotherapy using the PLF (cisplatin/leucovorin [folinic acid]/5-fluorouracil [FU]) regimen in these patients. Primary endpoints of the study were the toxicity and the response to chemotherapy. Secondary endpoints were the rate of complete resection, survival, and first site of failure.
Forty-nine patients with adenocarcinoma of the stomach were enrolled. Staging was based on abdominal computed tomography (CT) scans, endosonography, and laparoscopy. The intention was to administer two cycles (each containing six courses) of preoperative chemotherapy, consisting of cisplatin 50 mg/m(2), high-dose folinic acid (HD-FA) 500 mg/m(2), and HD 5-FU (HD-5-FU) 2000 mg/m(2) (PLF). Following chemotherapy all patients were referred to surgery. To be evaluable for response, survival, and first site of failure, the patient had to receive at least one cycle of chemotherapy.
Toxicity observed was low, with grade 3 toxicity in fewer than 5% of the patients and two events of grade 4 toxicity (diarrhea and pulmonary embolism). Forty-two of the patients (86%) received at least one cycle of chemotherapy. The clinical response rate in these patients was 26% (11/42 patients). In 76% of the patients (32/42), a complete resection was possible. The median duration of follow-up for the surviving patients was 58 months (range, 38 to 80+ months). The median survival time for the 42 patients assessable for response was 25.4 months (range, 6 to 80+ months). After complete resection, median survival time was 32 months (range, 7.6 to 80+ months). The median survival time for clinically responding patients has not yet been determined, but 5-year survival is 90%. Twenty of the 32 completely resected patients (62.5%) had recurrences. First site of failure was peritoneal dissemination in 10 patients; locoregional and distant recurrences were rare.
Neoadjuvant chemotherapy with PLF in patients with locally advanced gastric cancer has low toxicity and reasonable efficacy, allowing administration on an outpatient basis. Clinically responding patients have an excellent outcome after complete resection. The development of peritoneal dissemination even after neoadjuvant chemotherapy and complete resection remains an unsolved problem in patients with nonintestinal type tumors.
局部晚期胃癌（cT3、cT4、N+、M0）患者即便接受了根治性手术，预后仍较差。本研究旨在评估采用PLF（顺铂/亚叶酸钙/5-氟尿嘧啶）方案进行新辅助化疗对这些患者的毒性及疗效。该研究的主要终点为毒性及化疗反应。次要终点为根治性切除率、生存率及首次复发部位。
纳入49例胃腺癌患者。分期基于腹部计算机断层扫描（CT）、内镜超声及腹腔镜检查。计划给予两个周期（每个周期含六个疗程）的术前化疗，方案为顺铂50mg/m²、高剂量亚叶酸钙（HD-FA）500mg/m²及高剂量5-氟尿嘧啶（HD-5-FU）2000mg/m²（PLF）。化疗后所有患者均接受手术治疗。为评估反应、生存率及首次复发部位，患者必须接受至少一个周期的化疗。
观察到的毒性较低，3级毒性患者少于5%，4级毒性事件有两例（腹泻和肺栓塞）。42例患者（86%）接受了至少一个周期的化疗。这些患者的临床缓解率为26%（11/42例患者）。76%的患者（32/42）可行根治性切除。存活患者的中位随访时间为58个月（范围38至80+个月）。42例可评估反应的患者的中位生存时间为25.4个月（范围6至80+个月）。根治性切除后，中位生存时间为32个月（范围7.6至80+个月）。临床有反应患者的中位生存时间尚未确定，但5年生存率为90%。32例根治性切除患者中有20例（62.5%）复发。10例患者的首次复发部位为腹膜播散；局部及远处复发少见。
局部晚期胃癌患者采用PLF方案进行新辅助化疗毒性低、疗效合理，可在门诊给药。临床有反应的患者根治性切除后预后良好。对于非肠型肿瘤患者，即便新辅助化疗及根治性切除后仍发生腹膜播散，这一问题仍未解决。
