同步放疗联合替吉奥治疗老年局部晚期胃癌的疗效分析

目的探讨同步放疗联合替吉奥治疗老年局部晚期胃癌的临床效果。方法回顾性分析64例老年局部晚期胃癌患者,分为两组,对照组30例采用放疗,实验组34例在放疗基础上加用替吉奥胶囊15服,观察两组近期疗效及不良反应。结果实验组34例中完全缓解（CR）12例,部分缓解（PR）9例,稳定（SD）8例,病变进展（PD）5例,缓解率为61．8％;对照组30例中CR8例,PR5例,sD12例,PD5例,缓解率为43．3％,两组比较差异有统计学意义（P〈0．05）。实验组1年生存率70．6％（24／34）,对照组1年生存率46．7％（14／30）,差异具有统计学意义（P〈0．05）。两组患者不良反应无差别。结论同步放疗联合替吉奥可以有效提高老年晚期胃癌患者的近期缓解率和1年生存率,并且在提高其生活质量的同时不会加重不良反应。     

Feasibility study of adjuvant chemotherapy with S-1 (TS-1; tegafur, gimeracil, oteracil potassium) for gastric cancer

Background We conducted a feasibility study using S-1, a novel oral derivative of 5-fluorouracil, as postoperative adjuvant chemotherapy for curatively resected gastric cancer patients.Methods Adjuvant chemotherapy consisted of eight courses (4-week administration and 2-week withdrawal) of S-1, at 80–120mg/body per day. Forty-one patients from 11 institutions were enrolled in this pilot study, from November 1999 to October 2000.Results Thirty-five patients were eligible. In 7 patients, S-1 administration was discontinued due to recurrence. Among the 28 patients without recurrence, the planned eight courses of S-1 were administered to 17 patients (60.7%). In 4 patients, S-1 administration was discontinued due to subjective symptoms, such as anorexia, in the first course. Adverse reactions such as neutropenia, leukopenia, elevated total bilirubin, anorexia, general fatigue, diarrhea, nausea, and stomatitis were seen in more than half of the patients. Although grade 3 neutropenia (29.3%), leukopenia (9.8%), and diarrhea (9.8%) were observed, no grade 4 adverse effects appeared. Compared with the treatment of unresectable or recurrent gastric cancer with S-1, the incidence of adverse reactions in the adjuvant setting was slightly higher, probably due to the influence of gastrectomy.Conclusion Except for the early development of anorexia, most likely due to adverse effects of surgery, postoperative administration of S-1 for 1 year seems feasible as adjuvant chemotherapy for gastric cancer.     

替吉奥联合顺铂治疗晚期非小细胞肺癌的临床疗效

目的探讨替吉奥联合顺铂治疗晚期非小细胞肺癌(NSCLC)的临床疗效和安全性。方法选取2013年1月至2013年8月间收治的NSCLC患者118例,根据随机数字表法分为观察组和对照组,每组59例。对照组患者予以吉西他滨联合顺铂(GP方案)治疗,观察组患者予以替吉奥联合顺铂治疗,两组均以4周为1个周期,直至病情进展或死亡或出现不能耐受的不良反应而终止治疗。比较两组患者治疗后的临床疗效,评价无进展生存时间(PFS)与总生存时间(OS),并比较两组患者的急性与亚急性毒性反应。结果观察组患者部分缓解(PR)、客观缓解率(ORR)、疾病控制率(DCR)均高于对照组,而疾病进展(PD)低于对照组,中位PFS、中位OS均长于对照组,不良反应发生率均低于对照组,差异均有统计学意义(P<0.05)。结论替吉奥联合顺铂为治疗晚期NSCLC的临床疗效较好,患者生存时间延长,且不良反应发生率低,对晚期NSCLC的临床治疗有一定的指导和借鉴意义。     

多西紫杉醇联合替吉奥胶囊治疗晚期食管胃交界腺癌的临床观察

目的:探讨多西紫杉醇联合替吉奥胶囊治疗晚期食管胃交界腺癌的临床疗效和不良反应。方法:2009年1月—2011年1月经病理学确诊的58例晚期食管胃交界腺癌患者接受多西紫杉醇联合替吉奥胶囊治疗:多西紫杉醇35mg/m2静脉注射d1和d8,替吉奥胶囊胶囊每天70mg/m2d1～14,每3周为1个化疗周期。每2个化疗周期评价近期疗效。每个化疗周期后评价不良反应。对所有患者进行随访,评估生存情况。结果:58例患者均可评价疗效,其中完全缓解5例(8.6%)、部分缓解21例(36.2%),疾病稳定18例(31.0%),疾病进展14例(24.1%),有效率为44.8%(26/58)。中位TTP为8.0个月,MST为10.5个月。主要不良反应包括骨髓抑制、口腔炎、手足综合征和胃肠不良反应等。Ⅲ～Ⅳ级中性粒细胞减少发生率为25.9%(15/58)。结论:多西紫杉醇联合替吉奥胶囊治疗晚期食管胃交界腺癌的近期疗效较好,不良反应可以耐受。     

A case of Borrmann type 4 gastric cancer well responded to chemotherapy with tegafur

A 62-year-old female had unresectable stage 4 gastric cancer with ascites. She was treated with suppository administration of tegafur 750 mg/day. Endoscopical examination before treatment showed Borrmann 4 gastric cancer. After 3 months' treatment, the lesion almost disappeared. The patient survived for 9 months after the diagnosis.     

The first case of phenytoin intoxication associated with the concomitant use of phenytoin and TS-1, a combination preparation of tegafur, gimeracil, and oteracil potassium

PURPOSE: We reported the first case of phenytoin intoxication due to the concomitant use of phenytoin and TS-1, together with a review of the literature regarding the occurrence of phenytoin intoxication due to the concomitant use of phenytoin and fluoropyrimidine antitumor drugs such as fluorouracil (5-FU) and tegafur (FT). METHODS: We showed the clinical course of our patient. Reports of phenytoin intoxication due to the concomitant use of phenytoin and fluoropyrimidine antitumor drugs in the English and Japanese language literature up to 2007 were identified by searching Medline and ICHUSHI Web (Japana Centra Revuo Medicina). RESULTS: A patient taking phenytoin and TS-1, a combination preparation of tegafur, gimeracil, and oteracil potassium, experienced lightheadedness and repeated falls associated with an increase in serum phenytoin concentration (32.8 mug/ml) at 1 month after the start of TS-1 treatment. The time lag between initiation of combined treatment and onset of adverse symptoms suggests the presence of an indirect mechanism, rather than direct inhibition of drug-metabolizing enzymes by drugs in TS-1 or their active metabolites. CONCLUSIONS: Plasma phenytoin concentration should be closely monitored in patients receiving TS-1 and phenytoin concomitantly.     

Efficacy and safety of novel oral fluoropyrimidine anticancer drug, TS-1 for advanced and recurrent gastric cancer patients

The efficacy and safety of the oral fluoropyrimidine TS-1, which contains a dihydropyrimidine dehydrogenase (DPD) inhibitor, were examined in fifty-five patients with gastric cancer. The patients were divided into 28 with measurable cancer lesions (TUM group) and 27 without them (ADJ group). The total number of courses was 164 (mean: 5.9 courses) in the TUM group and 146 (mean; 5.4 courses) in the ADJ group. The response rate in the TUM group, excluding three patients who could not be evaluated because of incomplete administration, was 40% (CR: 4, PR: 6, NC: 6, PD: 9). Among responders, the mean number of courses to response was 2.2 and the median survival time (MST) was 21.7 months. In terms of safety, adverse reactions appeared in forty-five patients (82%) and the incidence was higher in the ADJ group. Major toxicities were leukopenia (38%), anorexia (27%), increased total bilirubin concentration (25%) and diarrhea (24%). Adverse reaction of grade 3 was found in only three patients (5.5%) and there were no drug-related deaths. In conclusion, TS-1 is safe and effective if attention is given to biweekly examinations for the development of adverse reactions.     

Three cases of advanced gastric cancer resected after successful treatment with the novel oral anticancer drug TS-1

We operated on 3 patients with advanced gastric cancer after successful treatment with novel oral 5-fluorouracil derivatives (TS-1). In all 3 patients, gastrointestinal fiberscopy revealed a considerable reduction in the tumor after oral administration of TS-1 in our clinic. Case 1 underwent surgery after an interval of 1 day following oral administration of TS-1 for 18 days. Pathologically, no cancer cells were found in the resected stomach and a few cancer cells were found only in resected lymph nodes. In case 2, who underwent surgery after an interval of 7 days following oral administration of TS-1 for 14 days, a few cancer cells were found only in the submucosal layer of the stomach and no viable cancer cells remained in the metastasized lymph nodes. In case 3, who underwent surgery after an interval of 11 days following administration of TS-1 for 26 days, scattered cancer cells, mostly fibrotic, were found as far as the subserosal layer. The pathological effectiveness of chemotherapy was grade 2 or 3 in each case. Case 2 and 3 followed a satisfactory postoperative course; however, case 1 suddenly had endotoxinemia on the 7th postoperative day. Although the patient had temporary multiple organ failure, he recovered eventually. All 3 patients have been well without any signs of recurrence for more than a year after surgery.     

A case of advanced gastric cancer resected after successful treatment with the novel oral anticancer drug TS-1

We report a case of advanced gastric cancer resected after successful treatment with the novel oral anticancer drug TS-1. The patient was a 52-year-old male. Gastrointestinal fiberscopy showed advanced gastric cancer. Examinations by computed tomography revealed gastric cancer invasion of the pancreas and swollen para-aortic lymph nodes. This patient was treated by preoperative chemotherapy with oral administration of TS-1 (120 mg per day). After 3 courses of treatment of TS-1, the primary lesion and swollen lymph nodes were remarkably reduced. This chemotherapy enabled total gastrectomy in curative resection. The pathological effectiveness of chemotherapy was Grade 1b in the primary lesion and Grade 2 or 3 in the lymph nodes. The patient sustained few side effects. This preoperative chemotherapy regimen seems to be an effective and promising therapy for patients with advanced gastric cancer.     

An oral anticancer drug, TS-1, enabled a patient with advanced gastric cancer with Virchow's metastasis to receive curative resection

We encountered a patient with advanced gastric cancer, with Virchow's lymph node metastasis, who subsequently underwent curative resection after neoadjuvant chemotherapy with the newly developed oral anticancer drug, TS-1. The patient was a 67-year-old woman who had a type 2 tumor in the middle third of the stomach, and Virchow's lymph node metastasis, which was diagnosed by fine-needle aspiration cytology; she also had swollen paraaortic lymph nodes. Curative resection was considered impossible, and TS-1 (100 mg/day) was administered for 28 days in one course, mainly in the outpatient clinic. Although grade 2 stomatitis interrupted the therapy on day 21 of the second course and on day 7 of the third course, the type 2 tumor showed marked remission (partial response; PR) and the metastasis in the Virchow's and paraaortic lymph nodes had completely disappeared after the third course (complete response; CR). Eleven weeks after the completion of the TS-1 treatment, total gastric resection with D3 lymph node dissection was performed. Histopathological examination revealed tumor involvement only in the mucosal and submucosal layers of the stomach and the no. 4d lymph node. Most of the tumor was replaced with fibrosis with granulomatous change in the muscularis propria of the stomach and in the no. 3, no. 6, and no. 7 lymph nodes. This may be the first report of a patient with advanced gastric cancer with Virchow's lymph node metastasis who successfully received curative resection following neoadjuvant chemotherapy with a single oral anticancer drug. Received: August 7, 2001 / Accepted: January 28, 2002     

A case of gastric cancer of Borrmann type IV complicated with carcinomatous peritonitis responding well to chemotherapy of tegafur only

A 46-year-old-male was admitted to our hospital with an unresectable stage of gastric cancer of Borrmann type IV with carcinomatous peritonitis. He was treated only with tegafur 900 mg/day. After 2 months' treatment, computed tomography showed ascites disappeared and a remarkable improvement was observed by barium meal study and endoscopic examination. The patient has survived for 12 months without any abdominal complaints and ascites since the beginning of treatment. Thus, this is a rare case responding well to chemotherapy of tegafur only.     

Efficacy and safety of S-1 (tegafur,gimeracil, and oteracil potassium) concurrent with 3-dimensional conformal radiotherapy for newly diagnosed squamous cell carcinoma of the lung in elderly patients

PurposeThis study evaluated the efficacy and safety of the combination drug tegafur, gimeracil, and oteracil potassium (S-1) concurrent with 3-dimensional conformal radiotherapy for newly diagnosed squamous cell carcinoma of the lung in elderly patients.Patients and methodsPatients with pathologically or cytologically newly diagnosed lung squamous cell carcinoma (n = 106) were randomly assigned to receive the combination of tegafur, gimeracil, and oteracil potassium (40 mg/m², BID, d1−28, repeated every 6 weeks for 4 cycles) and concurrent 3D-conformal radiotherapy (60 Gy; experimental group), or gemcitabine (800−1000 mg/m², d1 and d8) repeated every 21 days for 4 cycles as well as 3D-conformal radiotherapy (control group).ResultsThe overall response rate (complete and partial responses) of the experimental group was 68.6%, which was significantly higher than that of the control group (38.5%; P = 0.002). The median progression-free survival rates of the experimental and control groups were 11.8 months (95% confidence interval [CI]: 8.0 − 22.4) and 7.8 months (95% CI, 6.9–9.2), respectively (P = 0.017). Adverse reactions included grade I/II radiation esophagitis and pneumonitis, with good tolerance. Grade III/IV adverse reactions of the experimental and control groups were leucopenia (20% cf. 56.6%, respectively; P = 0.027), thrombocytopenia (3.9% cf. 25%; P = 0.037), and gastrointestinal reaction (1.9% cf. 3.5%; P = 0.35).ConclusionThe efficacy of concurrent combination chemotherapy with tegafur, gimeracil, and oteracil potassium (S-1) and 3D-conformal radiotherapy for newly diagnosed squamous cell carcinoma of the lung in elderly patients was excellent, and all toxicities were well tolerated. This treatment might be considered a main regimen in the management of squamous cell carcinoma of the lung in elderly patients.     

奥沙利铂联合替吉奥胶囊治疗晚期结直肠癌的临床观察

目的:观察奥沙利铂联合国产替吉奥胶囊方案治疗晚期结直肠癌的近期临床疗效及不良反应。方法:选择104例晚期结直肠癌患者,采用以下方案化疗,奥沙利铂130mg/m2,静脉滴入,d1;替吉奥胶囊80mg/(m2.d),分2次,餐后口服,d1～d14;28d为1个周期,至少完成2个周期。按RECIST1.1标准评价客观疗效和不良反应。结果:104例患者均可以评价疗效。完全缓解(CR)4例(3.8%),部分缓解(PR)48例(46.2%),稳定(SD)32例(30.8%),进展(PD)20例(19.2%),总有效率(CR+PR)为50.0%(52/100),临床控制84例(80.8%)。不良反应为消化道反应、骨髓抑制、周围神经毒性及手足口综合征等。结论:奥沙利铂联合替吉奥胶囊方案治疗晚期结直肠癌有临床疗效明确、患者依从性好、不良反应少、用药安全等特点。     

替吉奥与沙利度胺联合肝动脉栓塞化疗治疗中晚期肝细胞癌的临床观察

目的:观察经肝动脉栓塞化疗(TACE)单用或联合替吉奥与沙利度胺治疗中晚期肝细胞癌（HCC）的疗效。方法:将2010年8月-2012年8月本院收治的无法手术切除的中晚期HCC患者80例随机分为2组,每组40例。治疗组采用TACE联合替吉奥与沙利度胺口服,对照组仅行TACE治疗。比较两组的有效率、疾病控制率、生存率以及不良反应情况。结果:治疗组有效率67.5％,对照组30.0％,差异有统计学意义（P=0.001）;治疗组疾病控制率92.5％,对照组37.5％,差异有统计学意义（P=0.000）。治疗组1年生存率80.0％,对照组50.0％,差异有统计学意义（P=0.005）;治疗组2年生存率42.5％,对照组10.0％,差异有统计学意义（P=0.001）。两组不良反应轻微,主要为恶心呕吐、便秘和骨髓抑制,为I、II级,对症治疗可缓解,两组比较差异无统计学意义(P>0.05)。结论:替吉奥与沙利度胺联合TACE术对中晚期HCC有一定的治疗价值,值得进一步观察。     

Complete response in a case of unresectable gastric cancer with a combination of tegafur, 5-fluorouracil and mitomycin C

A 75-year-old man with gastric cancer metastatic to the liver was treated by combined administration of Tegafur (800 mg/body/day), 5-fluorouracil (300 mg/body/day) and Mitomycin C (hepatic arterial infusion of 20 mg/body and intravenous infusion of 8 mg/body). The total dose of Tegafur was 5.6 g, that of 5-FU was 11.4 g, and that of MMC was 36 mg for one month and a half. After therapy, primary and metastatic sites was completely disappeared. The patient has survived for 6 years 8 months in a state of complete response.     

Two elderly patients with advanced gastric cancer responding to chronomodulation chemotherapy with tegafur + cisplatin + isovorin followed by oral administration of S-1

Recently, as society ages there have become more elderly gastric cancer patients with/without several complications(cerebrovascular diseases, cardiac diseases, atherosclerosis, DM, etc.), that were non-resected and require highly effective chemotherapy and good QOL. We report two elderly gastric cancer patients responding to chronomodulation chemotherapy (tegafur + cisplatin + Isovorin) based on circadian rhythms plus a new antitumor drug, S-1. The treatment protocol was tegafur 800 mg/body, days 1-7 (continuing 16 h, intravenously with 500 mg/body from 16 to 0 h, 300 mg/body from 0-8 h, for non-uniform administration), cisplatin 10 mg/body, days 1-5, (16 h), Isovorin 25 mg/body, days 1-5, (16 h, oneshot infusion, for 4 courses followed by a week rest. Next was S-1 120 mg/body x 2 times orally for 28 days, followed by 2 weeks rest, the administered for another 28 days. The first patient was 74 years of age, with advanced type 3 plus early type IIc gastric cancers with liver metastasis (H1). After chemotherapy the liver metastasis disappeared, there was a 70% reduction in the advanced cancer and the early cancer disappeared. The second patient was 84 years of age, with advanced type 3 gastric cancer invading the esophagus. After chemotherapy, the primary lesion was reduced 80% and the esophageal invasion mass shrunk. The only adverse effect was grade 2 pancytopenia. In conclusion this regimen resulted in good intrachemotherapeutic QOL and highly effective performance in elderly advanced gastric cancer patient.     

老年食管癌替吉奥同期放疗的临床疗效观察

目的:探讨替吉奥同期放疗治疗老年食管癌的疗效及其不良反应.方法:80例老年食管鳞状细胞癌患者随机法分为单纯放疗组(RT组)40例和替吉奥同期放疗组(CRT组)40例.CRT组放疗剂量50.4 Gy/28次,RT组63.0 Gy/35次.结果:CRT和RT组患者的有效率分别为85.0％(34/40)和65.0％(26/40),差异有统计学意义,P=0.039.CRT组患者的中位生存期为21.0个月,RT组为15.5个月,差异有统计学意义,P=0.044.CRT和RT组患者3年生存率分别为32.5％和12.5％.毒副反应发生率差异无统计学意义.结论:对于老年食管癌患者,可采用替吉奥同期放疗的治疗方法,以期获得更好的疗效及长期生存.     

Dose intensity of uracil and tegafur in postoperative chemotherapy for patients with poorly differentiated gastric cancer

A retrospective analysis of postoperative chemotherapy had shown the continuous administration of UFT, an oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, to be effective for poorly differentiated gastric cancer. We therefore sought to determine prospectively the effective dose of postoperative chemotherapy with UFT for patients with poorly differentiated gastric cancer following a curative resection. We determined the effect of the combined intravenous administration of mitomycin C (MMC) and oral treatment with protein-bound polysaccharide Kreha (PSK), extracted from the basidiomycete Coriolus versicolor, and UFT at a dose of either 8 mg/kg or 12 mg/kg daily for 1 year. A total of 224 patients with poorly differentiated stage II–IV gastric cancer were entered into this study after undergoing a curative resection. No differences were observed between the two treatment groups in terms of prognostic factors, the toxicity rate or the doses of the drugs prescribed, other than UFT. The higher dose of UFT in maintenance therapy led to a decrease in the recurrence rate (P < 0.05), and increases in disease-free survival and cause-specific survival (P < 0.05). UFT at 12 mg/␣kg in postoperative chemotherapy was thus found- to improve the postoperative results with no increase in toxicity for poorly differentiated gastric cancer, and is also cost-effective for outpatients. Received: 8 February 1996 / Accepted: 27 November 1996     

Prolonged survival of a patient with lung cancer after treatment with S-1, a new oral fluoropyrimidine anticancer drug

A 36-yr-old woman complaining of cough and body weight loss at a health checkup and referred to us after an abnormality was noted on the chest X-ray was diagnosed with clinical stage IV (cT2N3Ml) non-small-cell lung cancer (adenocarcinoma). She received three courses of chemotherapy. The response to treatment was stable disease. She was subsequently enrolled in a clinical trial of S-1, a new oral fluoropyrimidine anticancer drug, and received a total of 22 courses of S-1 over a period of 2 yr 5 mo. At the end of treatment, she was classified as having a partial response. A bronchoscopic biopsy disclosed no cancer cells. Remission continued for 1 yr 7 mo after treatment. The patient died of primary disease 8 yr after the initiation of treatment with oral S-1. Non-small-cell lung cancer was approved as a new indication of S-1 in 2004 in Japan, but the number of patients receiving it for this indication remains limited. Here, we describe our experience with a patient with adenocarcinoma of the lung who survived for a prolonged period after treatment with S-1. Our findings suggest that S-1 is effective for the treatment of non-small-cell lung cancer.