Phase I trial of Uracil-Tegafur (UFT) plus oral leucovorin: 14-day schedule

We previously reported results of a Phase II trial of UFT [Taiho Pharmaceutical Ltd., Tokyo, Japan; (BMS-200604) Bristol-Myers Squibb, Princeton, NJ], an oral 4:1 molar concentration of uracil and tegafur, plus oral leucovorin for metastatic colorectal carcinoma (Pazdur et al, J. Clin. Oncol. 12:2296-2300, 1994]. Our results demonstrated that a 28-day schedule of this combination produced a response rate similar to that obtained with conventional intravenous fluorouracil (5-FU)-plus-leucovorin regimens but without the severe or life-threatening neutropenia or oral mucositis that complicates intravenous 5-FU regimens. The current Phase I trial examines the dose-limiting toxic effects and maximum tolerated dose of a 14-consecutive-day schedule of UFT plus oral leucovorin in 14 patients who had histologically proven cancer and had received prior chemotherapy. The daily UFT plus leucovorin dose was divided into three doses administered orally every 8 hours. In this study, the UFT dose was escalated while the leucovorin dose remained at 150 mg/day. Of the 14 patients, 4 were initially treated at the 350-mg/m²/day UFT level for 14 days without any dose-limiting toxic reactions. Subsequently, another 7 patients were treated at the 400-mg/m²/day level; grade 3 diarrhea developed in 3 of these 7 (with severe abdominal cramping in 2 cases and severe nausea and vomiting unresponsive to antiemetics in the third). To better define the starting dose for phase II studies, an additional 3 patients were treated at the 350-mg/m²/day dose level. Of the total 7 patients treated at 350 mg/m²/day, grade 3 toxic events (diarrhea) developed in 2 patients. Grade 1-2 toxic effects noted at this level included fatigue, stomatitis, skin rash, abdominal pain, nausea, and vomiting. Neither partial nor complete responses were observed in this trial. The maximum tolerated dose of this schedule is 350 mg/m²/day UFT plus 150 mg/day oral leucovorin. However, because of this schedule's inferior dose intensity compared with that of the 28-day schedule of UFT plus leucovorin, subsequent development of UFT in the United States has focused on the 28-day regimen.     

Complete disappearance of recurrent hepatocellular carcinoma with peritoneal dissemination and splenic metastasis: a unique clinical course after surgery

Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. We report a case of complete disappearance of intrahepatic, peritoneal and splenic metastases in HCC after hepatectomy using treatment with tegafur and uracil (UFT). The effect of UFT alone was not likely to have caused the disappearance of this tumour because HCC recurrence advance markedly within 5 months of surgery despite oral administration of UFT. This case demonstrates a unique postoperative clinical course that suggests spontaneous regression of HCC. This is the first case of complete disappearance of unresectable HCC with peritoneal seeding and splenic metastasis.     

替加氟有关物质的色谱-质谱结构鉴定

目的采用色谱-质谱联用技术鉴定替加氟有关物质,为其工艺和质量控制提供参考依据。方法采用十八烷基硅烷键合硅胶的填充剂,流动相为乙腈-甲醇-10 mmol·L-1醋酸铵缓冲溶液,对替加氟有关物质进行分离;采用电喷雾正离子化-飞行时间质谱法测定各有关物质的准确质量,三重四极杆质谱测定子离子特征,并经解析鉴定各杂质结构。结果与结论替加氟与其有关物质分离良好,检测出4个主要有关物质均为替加氟合成的起始原料,是母核基本未发生变化,仅5位被不同基团取代的衍生物。     

Chemotherapy with enteric-coated tegafur/uracil for advanced hepatocellular carcinoma

Hepatocellular carcinoma （HCC） is one of the most common malignancies worldwide, including Japan. Although the development of imaging modalities has made the early diagnosis of HCC possible, surgically resectable cases are relatively uncommon because of hepatic function reserve and/or an advanced stage at presentation. Several modalities, such as transcatheter arterial chemoembolization, percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation are reportedly useful in treating patients with non-resectable disease. However, unfortunately, many HCC patients have tumor recurrence. The overall prognosis of patients with HCC is very poor, and treatment of the advanced form is still problematic. In this article, we review the clinical efficacy and toxicity of enteric-coated tegafur/uracil in the treatment of patients with advanced non-resectable HCC.     

奥沙利铂联合替吉奥治疗晚期胃癌的效果

目的探讨奥沙利铂联合替吉奥治疗晚期胃癌的效果。方法2011年3月-2013年1月,我院收治的晚期胃癌病人56例,随机分为实验组和对照组,每组28例。实验组采用奥沙利铂联合替吉奥治疗,而对照组采用FOLFOX4方案治疗。结果两组疗效比较差异无显著性（P〉0．05）,而两组的肿瘤控制率比较差异有显著性（x2=2．13,P〈0．05）;两组不良反应主要为恶心呕吐、腹泻、末梢神经炎、血小板减少、血红蛋白减少、白细胞减少;实验组FACT—G评分提高率及降低率明显高于对照组（x2=6．23、5．72,P〈0．05）。结论奥沙利铂联合替吉奥治疗晚期胃癌具有协同作用,其疗效满意,可以明显提高肿瘤控制率并减少药物毒性。     

A phase II study of weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin as first-line chemotherapy in patients with locally advanced or metastatic gastric cancer

Background:

Docetaxel plus cisplatin and 5-fluorouracil has become a new standard for treating advanced gastric cancer. However, high rates of severe neutropenia limit its application. Modification of the regimen could be the solution to get similar activity but less myelosuppression.

Methods:

Patients with histologically confirmed, locally advanced, or recurrent/metastatic gastric adenocarcinoma without previous chemotherapy were enrolled. This regimen consisted of docetaxel (Tyxan, TTY, Taipei, Taiwan) 30-min infusion at a dose of 36 mg m⁻², followed by cisplatin 30 mg m⁻² infusion over 1 h on days 1 and 8, and oral tegafur/uracil 300 mg m⁻² per day plus leucovorin 90 mg per day on days 1–14, every 3 weeks. Tumour response was evaluated after every 2 cycles of treatment.

Results:

From August 2007 to March 2009, 45 patients were enrolled. The median age was 56 years (range: 22–75). Among the 40 patients evaluable for tumour response, one achieved a complete response, 22 had partial responses and 11 had stable disease. The overall response rates of the evaluable and intent-to-treat (ITT) populations were 58% (95% CI: 41–74%) and 53% (95% CI: 38–68%), respectively. The disease control rates in these populations were 85% (95% CI: 70–94%) and 82% (95% CI: 68–92%), respectively. In the ITT analysis, the median time to progression and overall survival were 6.8 and 13.9 months, respectively. Major grade 3–4 toxicities were neutropenia (51%), anaemia (22%), diarrhoea (16%), and infections (20%). No patient died of treatment-related toxicities.

Conclusion:

Concurrent weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin are effective and well tolerated in the treatment of advanced gastric cancer.     

SOX和TP方案治疗晚期三阴性乳腺癌的临床疗效及生存情况的比较

目的探讨奥沙利铂联合替吉奥(SOX)方案和奥沙利铂联合多西他赛(TP)方案在晚期三阴性乳腺癌治疗中的临床疗效及对生存时间的比较。方法选取82例晚期乳腺癌患者,根据最终选取的治疗方案分为SOX组(n=44)和TP组(n=38),观察两组患者近期疗效和不良反应,检测两组患者治疗前后糖类抗原153(CA153)和癌胚抗原(CEA)水平,并随访两组患者的生存情况。结果 SOX组和TP组患者近期疗效比较,差异无统计学意义(P﹥0.05),总缓解率分别为31.82%和31.58%;SOX组和TP组患者治疗后CA153和CEA比较,差异均无统计学意义(P﹥0.05);SOX组和TP组患者不良反应发生率比较,差异均无统计学意义(P﹥0.05);SOX组和TP组患者中位无进展生存时间分别为7.45个月(95%CI:6.40～8.50)和7.50个月(95%CI:6.91～8.09),中位总生存时间分别为14.00个月(95%CI:12.40～15.60)和13.00个月(95%CI:10.98～15.02),差异均无统计学意义(P﹥0.05)。结论 SOX和TP方案在晚期三阴性乳腺癌治疗中的临床疗效相当,值得临床应用。     

Chemoradiotherapy and adjuvant chemotherapy for rectal cancer

Local recurrence is an important factor in determining the outcome of patients after surgery for rectal cancer, and various attempts have been made to reduce the local recurrence rate. Randomized controlled trials have shown that radiotherapy combined with total mesorectal excision can reduce the local recurrence rate in rectal cancer patients who undergo curative surgery. Chemoradiotherapy is more effective in achieving local control than radiotherapy alone, and preoperative chemoradiotherapy is superior to postoperative chemoradiotherapy in terms of adverse events. Recent advances have led to the identification of potential therapeutic targets such as epidermal growth factor receptor, vascular endothelial growth factor, and endothelial receptors. These new agents have been used in combination with conventional chemoradiotherapy, and higher pathological complete response rates have been reported for such combinations in comparison with conventional regimens. With regard to lateral node dissection, a recent study showed that postoperative chemoradiotherapy was more effective in reducing the local recurrence rate than lateral node dissection. As for adjuvant chemotherapy, one randomized controlled trial showed that patients who received uracil and tegafur as adjuvant therapy had significantly prolonged relapse-free survival times and overall survival times. As well, one metaanalysis has shown the efficacy of oral uracil-tegafur as adjuvant chemotherapy for rectal cancer.     

奈达铂与替加氟联合治疗中晚期食管癌的临床观察

目的：观察奈达铂与替加氟联合治疗中晚期食管癌的临床疗效。方法：21例中晚期食管癌患者应用国产奈达铂20mg/d加入生理盐水500ml中,静脉滴注2h;随后应用替加氟注射液,1000mg/d,静脉点滴。两种药物连续使用5天,每21天为1个周期,至少进行2个周期后评价。结果：21例患者中19例可评价疗效,平均每个病例2.95个周期。CR0例,PR9例（47.4%）,SD6例（31.6%）,PD4例（21.1%）,RR为47.4%。主要毒副反应为骨髓抑制。结论：奈达铂与替加氟联合治疗中晚期食管癌疗效较好,毒副反应较小,值得临床推广应用。