Clinical evaluation of prolonged chemotherapy combined with induction of hepatic drug-metabolizing enzymes as an adjuvant for treating patients with gastric cancer

A clinical trial of a protracted adjuvant cancer chemotherapy was carried out on 207 patients with operable gastric cancer, from April, 1977, in the First Department of Surgery, Chiba University Hospital and two closely related hospitals. These patients were given intravenously 0.4 mg/kg and 0.2 mg/kg of mitomycin C on the day of operation and the next day, respectively, and then 16 mg/kg intravenously of Futraful (FT-207) daily from the 10th postoperative day until discharge, followed by oral administration of FT-207, 12 mg/kg, for 24 to 36 months after discharge. Two mg/kg of phenobarbital and 30 mg/kg of glutathione were administered randomly to half the number of patients (induction group) to induce hepatic drug-metabolizing enzymes. Significantly higher levels of serum 5-Fluorouracil (5-FU) released from FT-207 were found in the induction group than in the controls. Five-year overall survival rates in the induction and control groups revealed no difference. However, the survival rates in Stage III patients in the induction group were significantly superior in the 3–5 postoperative years, compared to those in the Statge III of the control group, while Stage I, II and IV patients apparently received no benefit from this induction treatment.     

Intensified cancer chemotherapy by induction of hepatic drug-metabolizing enzymes as a trial for the treatment for stomach cancer

Studies of an intensified chemotherapy of FT-207, combined with MMC, have been under way since April 1977 in the First Department of Surgery of Chiba University Hospital and five closely related hospitals. These studies were performed on 114 patients with curative stomach cancer. The 114 patients received intravenously 0.4 mg/kg and 0.2 mg/kg of MMC on the operation day and the next day, respectively, and then intravenously 800 mg of FT-207 daily from the 10th postoperative day until discharge, followed by oral administration of FT-207, 600 mg, for more than 1 year after discharge. The 114 patients were divided into two groups. Half of the patients received 100 mg of phenobarbital and 30 mg/kg of glutathione for the purpose of induction of hepatic drug-metabolizing enzymes (induction group). Significantly higher levels of serum 5-FU released from FT-207 were observed in the patients of the induction group when compared to those of the control group. However, there was no statistically significant difference in survivals at both 12 and 24 months after operation between both groups.     

Intensified cancer themotherapy by induction of hepatic drug-metabolizing enzymes as a trial for the treatment for stomach cancer

Studies of an intensified chemotherapy of FT-207, combined with MMC, have been under way since April 1977 in the First Department of Surgery of Chiba University Hospital and five closely related hospitals. These studies were performed on 114 patients with curative stomach cancer. The 114 patients received intravenously 0.4 mg/kg and 0.2 mg/kg of MMC on the operation day and the next day, respectively, and then intravenously 800 mg of FT-207 daily from the 10th postoperative day until discharge, followed by oral administration of FT-207, 600 mg, for more than 1 year after discharge. The 114 patients were divided into two groups. Half of the patients received 100 mg of phenobarbital and 30 mg/kg of glutathione for the purpose of induction of hepatic drug-metabolizing enzymes (induction group). Significantly higher levels of serum 5-FU released from FT-207 were observed in the patients of the induction group when compared to those of the control group. However, there was no statistically significant difference in survivals at both 12 and 24 months after operation between both groups.     

复方苦参注射液对术后胃癌DFC方案辅助治疗毒副反应的影响

目的观察复方苦参注射液对术后胃癌DFC方案辅助治疗的毒副反应的影响。方法将手术后经病理证实分期为Ⅱ、Ⅲ期的胃癌患者作为研究对象,随机分为复方苦参注射液联合DFC方案组（研究组）20例及单纯DFC方案组（对照组）20例。结果研究组白细胞减少、消化道反应及乏力的发生率显著少于对照组（P〈0.05）,肝毒性也显著少于对照组（P〈0.05）。结论复方苦参注射液能减少DFC方案化疗毒副作用,增加患者化疗耐受性。     

Intraarterial chemotherapy as an adjuvant treatment in locally advanced gastric cancer

Background and aims D₂ gastrectomy has improved survival in gastric cancer. Adjuvant intravenous chemotherapy, radiotherapy, or multimodal therapy has failed to demonstrate improved survival. The results of intraarterial chemotherapy (IARC) as an adjuvant have been encouraging in a few studies. A prospective randomized trial was designed to evaluate the toxicity and survival in locally advanced gastric cancer using IARC as an adjuvant after potentially curative gastrectomy. Patients and methods Forty patients with locally advanced gastric cancer were randomly selected to undergo either potentially curative gastrectomy and receive IARC (study group) or gastrectomy only (control group). Clinical and histopathologic data were analyzed and the toxicity related to IARC was recorded. Results The groups were comparable (p>0.05). Three patients in the study group had minor toxicity. Five-year survival rate for the study and the control group was 52 and 54%, respectively (p>0.05). Mean survival for the study and the control group was 50±8 and 62±10 months, respectively (p>0.05). The number of recurrences and the failure sites were comparable (p>0.05). Conclusion Intraarterial chemotherapy can be safely applied to gastric cancer patients. As proposed by the protocol, the method cannot be recommended as an adjuvant treatment for locally advanced tumors because it appears that there is no survival benefit compared to potentially curative gastrectomy alone.     

Review of adjuvant chemotherapy for gastric cancer

Controlled randomized studies that compared surgery alone to adjuvant chemotherapy for gastric cancer were reviewed. The amount of residual tumor after surgery, selection of drug regimens, compliance with drug administration, and trial design seem to be responsible for the success of adjuvant chemotherapy. Though there are few beneficial regimens of adjuvant chemotherapy with statistical significance, single drug therapy with mitomycin C (MMC) and combination therapy with 5-fluorouracil (5FU) and methyl-CCNU, MMC/5FU/cytosine arabinoside (MFC), and 5FU/Adriamycin/MMC (FAM) seem to have potential survival benefit for patients with curative surgery. Incorporation of new drugs into adjuvant or neoadjuvant chemotherapy might open a new aspect of multimodality therapy for gastric cancer.     

Gastrojejunostomy as induction treatment for S-1-based chemotherapy in patients with incurable gastric cancer

Purpose  The development of new generation anticancer agents, including the oral drug, S-1, may alter the clinical importance of gastrojejunostomy in the treatment of incurable gastric cancer. We reviewed a series of patients who underwent gastrojejunostomy for this reason between 2002 and 2005. Methods  Fourteen patients underwent gastrojejunostomy followed by S-1-based chemotherapy for incurable gastric cancer with obstruction or stenosis of the gastric outlet at Niigata University Medical and Dental Hospital and two affiliated hospitals. The safety of gastrojejunostomy, outcome of palliation, and survival time were analyzed retrospectively. We compared the survival times with those of patients who underwent palliative gastrectomy or exploratory laparotomy between 1987 and 2001. Results  The median operative time and blood loss were 153 min and 66 ml, respectively. There were no major complications. The median starting time for chemotherapy after gastrojejunostomy was 15.5 days. All patients were discharged after gastrojejunostomy, and the median postoperative home stay ratio was 68%. The median survival time after gastrojejunostomy was 354 days, which was significantly longer than that of patients who underwent palliative gastrectomy or exploratory laparotomy. Conclusion  Gastrojejunostomy for incurable gastric cancer contributes not only to improving quality of life (QOL), but to prolonging survival through the induction and maintenance of S-1-based chemotherapy.     

Clinical evaluation of midazolam as an anesthetic for geriatric patients and patients with hepatic dysfunction

This study evaluated the usefulness of midazolam in inducing a anesthetic state in 60 patients who underwent surgery under general anesthesia. The patients were divided into 3 groups; a geriatric group, a hepatic dysfunction group, and a control group (adults without complications). To induce sleep 0.15 mg.kg-1 or 0.2 mg.kg-1 of midazolam was administered intravenously to all three groups. After the administration of midazolam, the mean time for obtaining absence of response to calling name and absence of ciliary reflex were not significantly different in the three groups. The pulse rate and respiratory rate also did not change remarkably. But significant decreases were observed in the systolic blood pressure and tidal volume in all three groups. However, they were not significantly different among the three groups. These results indicate that midazolam is a useful drug for inducing anesthetic state in geriatric patients and patients with hepatic dysfunction.     

胃癌辅助化疗的系统评价

胃癌的发病率和死亡率在消化道恶性肿瘤中都位居前列，虽然以手术为中心的综合治疗已成为当前公认的实体肿瘤的治疗策略，但对胃癌而吉，辅助化学治疗的作用和价值还存在争议。     

延长针刺式空肠造口置管肠内营养在胃癌术后辅助化疗中应用

目的 探讨延长针刺式空肠造口置管肠内营养在进展期胃癌术后辅助化疗中应用的可行性及其临床疗效。方法 将72例进展期胃癌术后辅助化疗患者随机分成A、B两组,每组36例;两组病例均于术中放置针刺式空肠造口管,A组延长空肠造口管留置时间至6个化疗疗程结束,每个化疗疗程经空肠造口管给予肠内营养液瑞能,每天1500ml,共7天,B组则于化疗前拔除空肠造口管,每个化疗疗程给予等热量普通饮食;观察A组延长空肠造口管留置及肠内营养并发症的发生率,比较两组化疗期间呕吐发生率及平均每日摄入量,比较两组化疗前后体重、血红蛋白、血清白蛋白、前白蛋白、转铁蛋白及血清白介素-2、NK细胞活性、T淋巴细胞亚群（CD^3＋、CD^4＋、CD^8＋）比例的变化情况。结果 A组延长空肠造口管留置及肠内营养无严重并发症发生;化疗期间A组呕吐发生率显著少于B组,平均每日摄入量显著多于B组;A组化疗前后体重、血红蛋白、血清白蛋白、前白蛋白、转铁蛋白、IL-2、NK细胞活性、CD3＋、CD4＋、CD8＋比例变化显著少于B组（P〈0.001）。结论 进展期胃癌术后辅助化疗期间延长针刺式空肠造口置管肠内营养是安全可行的,并具有减轻化疗呕吐,提高患者摄入量等优点,可以减少化疗药物对患者营养及免疫状况的影响,提高患者术后辅助化疗的耐受性及治疗效果。     

Clinical evaluation of schizophyllan adjuvant immunochemotherapy for patients with resectable gastric cancer —A randomized controlled trial—

Adjuvant immunochemotherapy using schizophyllan (SPG), an extract from the culture broth ofSchizophyllum commune Fries, was prescribed at random for 326 Japanese patients with resectable gastric cancer. The overall survival rates for 3 years did not differ between the SPG and control groups. In 62 patients with stage I gastric cancer and 67 with stage II, there was little difference in the 3-year survival rates. The survival rates for 100 patients with stage III were enhanced at p=0.0811 in the SPG group, as compared to the controls. The survival rates in 97 patients with stage IV cancer were much the same. These results warrant further application of this immunopotentiating drug for treating patients with resectable gastric cancer.     

新辅助化疗对进展期胃癌手术风险的研究

目的评估新辅助化疗对进展期胃癌手术风险的影响。方法全组27例患者,均经胃镜活检确诊为腺癌,采用FOLFOX-6方案术前化疗2个周期。结果有效率为50.0%(13/27),手术风险无增加,主要不良反应为胃肠道反应,骨髓抑制和周围神经毒性。结论FOLFOX-6方案作为进展期胃癌新辅助化疗方案安全有效,值得临床推广应用。     

Prolonged survival of gastric cancer patients on a specific adjuvant chemotherapy

Since 1970, there has been a remarkable improvement in Japan in the outcome of surgery for patients with gastric cancer. Not only the increased rate of detection of early gastric cancer but the standardization of the prophylactic extended lymphadenectomy (ELX) has brought about a remarkable rise in survival rate. In patients with regional lymph node metastasis, we obtained a 5 year survival rate of 39 percent in the ELX group, whereas the rate was only 18 percent in the simple gastrectomy group. The difference was statistically significant (P<0.001). As to adjuvant chemotherapy, the Cooperative Study Group of Surgical Adjuvant Chemotherapy for Gastric Cancer found in data on 1,805 patients followed for 5 years that the protocol, intraoperative bolus intravenous injection of Mitomycin C (MMC) plus oral administration of Futraful (Tegafur) for 3 months, concomitantly applied with ELX, proved to be effective for improving the survival of patients with advanced cancer such as stage III and positive lymph node metastasis with obvious serosal invasion. The 5 year survival rate of Japanese patients with gastric cancer after resective surgery was an overall 56 percent, 48 percent when confined to those with stage III cancer.     

Prospective randomized trial of early postoperative intraperitoneal chemotherapy as an adjuvant to resectable gastric cancer.

OBJECTIVE: Surgeons have postulated on numerous occasions that cancer resection may participate in the dissemination of a malignancy. This randomized trial sought to determine whether a large volume of chemotherapy solution used perioperatively to flood the peritoneal cavity could eliminate microscopic residual disease and thereby improve survival of patients with gastric cancer. SUMMARY BACKGROUND DATA: Surgical treatment failures in patients with gastric cancer are confined to the abdomen in most patients. Resection site and peritoneal surface spread, along with liver metastases, are the most common areas of recurrence. Survival and quality of life of patients with gastric cancer would be improved if disease progression at these anatomic sites was reduced. METHODS: In a prospective randomized trial of 248 patients, intraperitoneal mitomycin C on day 1 and intraperitoneal 5-fluorouracil on days 2 through 5 were administered after gastric cancer resection. Patients who were thought to have stage II or stage III disease were randomized after resection to surgery alone versus surgery plus early postoperative intraperitoneal chemotherapy. After final pathologic examinations, there were 39 patients with stage I, 50 with stage II 95 with stage III, and 64 with resected stage IV cancer. RESULTS: The 5-year survival of the surgery-only group was 29.3%, and the surgery-plus-intraperitoneal chemotherapy group was 38.7% (p = 0.219). In a subset analysis, the patients with stage I, stage II, and stage IV disease showed no statistically significant difference in survival. The 5-year survival rate of patients with stage III disease who underwent surgery only was 18.4% versus a survival rate of 49.1% for patients who underwent surgery plus intraperitoneal chemotherapy (p = 0.011). CONCLUSIONS: In a subset analysis, patients with stage III gastric cancer have shown a statistically significant improvement in survival when treated with perioperative intraperitoneal chemotherapy. Further studies in patients with gastric cancer with surgically directed chemotherapy are suggested.     

Clinical evaluation of schizophyllan adjuvant immunochemotherapy for patients with resectable gastric cancer--a randomized controlled trial

Adjuvant immunochemotherapy using Schizophyllan (SPG), an extract from the culture broth of Schizophyllum commune Fries, was prescribed at random for 326 Japanese patients with resectable gastric cancer. The overall survival rates for 3 years did not differ between the SPG and control groups. In 62 patients with stage I gastric cancer and 67 with stage II, there was little difference in the 3-year survival rates. The survival rates for 100 patients with stage III were enhanced at p = 0.0811 in the SPG group, as compared to the controls. The survival rates in 97 patients with stage IV cancer were much the same. These results warrant further application of this immunopotentiating drug for treating patients with resectable gastric cancer.     

胃癌腹腔灌注化疗的应用

术后腹腔转移是胃癌治疗失败的主要原因之一,而且一旦发生转移就很难进行有效治疗.腹腔灌注是有望最大程度的减少术后胃癌腹腔转移的有效手段之一.因此本文就针对灌注化疗的应用背景、临床疗效和药物选择等问题进行文献回顾.