S-1 monotherapy as second line chemotherapy in advanced gastric cancer patients previously treated with cisplatin/infusional fluorouracil

The treatment choice of advanced gastric carcinoma after failure from first-line therapy is quite limited. To evaluate the efficacy and toxicity of S-1 monotherapy in patients with advanced gastric cancer after failure of first line cisplatin and fluorouracil combination (CF). S-1 monotherapy as a second line treatment was given to the patients who had failed to CF combination in SC-101 study. The efficacy and toxicity of S-1 monotherapy were evaluated exploratory. The results indicated that forty-one patients received S-1 as a second line therapy after disease progression. The overall response rate and disease control rate were 14.6% and 41.5%, respectively. The median progression free survival (PFS) was 5.1 months (range: 2.9~6.2 month). The median overall survival time was 6.4 months. The survival rates at 6 month and 1 year were 56% and 7.3%, respectively. Grade 3/4 adverse events were uncommonly occurred, including anemia (2.4%), neutropenia (2.4%), thrombocytopenia (4.9%) and rash (2.4%). There were no unexpected or life-threatening toxicities. Only one patient experienced dose reduction due to grade 3 rash. In conclusion, S-1 monotherapy provided a mild response rate and overall survival, and a favorable toxicity profile in the second line setting after the first line failure to cisplatin and fluorouracil combination.     

S-1 monotherapy as second line chemotherapy in advanced gastric cancer patients previously treated with cisplatin/infusional fluorouracil

The treatment choice of advanced gastric carcinoma after failure from first-line therapy is quite limited. To evaluate the efficacy and toxicity of S-1 monotherapy in patients with advanced gastric cancer after failure of first line cisplatin and fluorouracil combination (CF). S-1 monotherapy as a second line treatment was given to the patients who had failed to CF combination in SC-101 study. The efficacy and toxicity of S-1 monotherapy were evaluated exploratory. The results indicated that forty-one patients received S-1 as a second line therapy after disease progression. The overall response rate and disease control rate were 14.6% and 41.5%, respectively. The median progression free survival (PFS) was 5.1 months (ange: 2.9~6.2 month). The median overall survival time was 6.4 months. The survival rates at 6 month and 1 year were 56% and 7.3%, respectively. Grade 3/4 adverse events were uncommonly occurred, including anemia (2.4%), neutropenia (2.4%), thrombocytopenia (4.9%) and rash (2.4%). There were no unexpected or life-threatening toxicities. Only one patient experienced dose reduction due to grade 3 rash. In conclusion, S-1 monotherapy provided a mild response rate and overall survival, and a favorable toxicity profile in the second line setting after the first line failure to cisplatin and fluorouracil combination.     

Pharmacokinetics of gamma-hydroxybutylic acid (GHB) and gamma-butyrolactone (GBL), the anti-angiogenic metabolites of oral fluoropyrimidine UFT, in patients with gastric cancer.

Gamma-hydroxybutylic acid (GHB) and gamma-butyrolactone (GBL), the metabolites of UFT, which is an oral fluoropyrimidine, have been reported to inhibit angiogenesis with IC50 values of 25.8 ng/ml. The pharmacokinetics of GHB and GBL were examined after the administration of UFT in patients with gastric cancer. The patients received 200 mg of UFT orally twice a day. Peripheral blood samples were collected at 0, 0.5, 1, 2 and 4 hr after the time of dosing on day 5. The baseline and endogenous GBL concentrations in plasma were 20.2 +/- 7.5 ng/ml for patients and 16.8 +/- 4.0 ng/ml for volunteers (P = 0.221). The values of C(max) for tegafur, uracil, 5-FU and GBL were 14.7 +/- 5.2 and 4.0 +/- 2.8 microg/ml, 191.2 +/- 115.3 and 147.5 +/- 57.3 ng/ml, respectively, and the values of Tmax were 1.0 +/- 0.6, 1.1 +/- 0.6, 0.9 +/- 0.6 and 1.2 +/- 0. 6 hr, respectively. The concentration of GBL was much higher than its IC50 value for angiogenesis. GBL is thus suggested to contribute to the anticancer effects of UFT in addition to that of 5-FU, which is continuously metabolized from UFT.     

单药替吉奥胶囊治疗老年晚期胃癌的临床观察

目的：观察单药替吉奥胶囊治疗晚期胃癌的临床疗效及毒副反应。方法：选择50例经病理证实的老年晚期胃癌患者,随机分为治疗组32例及对照组18例。治疗组根据体表面积给予替吉奥胶囊治疗,对照组给予营养等最佳支持治疗。每2周期后行影像学检查评价疗效、记录不良反应及随访情况。结果：治疗组32例患者CR(完全缓解)0例,PR(部分缓解)10例,SD(病情稳定)12例,PD(病情进展)10例,临床总缓解率31.3%,临床获益率68.8%。治疗组中位无疾病进展时间及中位生存期分别为5.7及11.5个月,对照组分别为3.1及7.6个月。毒副反应主要为I-III度骨髓抑制、消化道反应、肝功能损伤及手足综合症。结论：单药替吉奥胶囊治疗老年晚期胃癌效果肯定,生活质量高、毒副作用小。     

Molecular pathology of familial gastric cancer, with an emphasis on hereditary diffuse gastric cancer

Gastric cancer is one of the major causes of cancer-related death worldwide. Familial clustering is observed in about 10% of cases; 1-3% of cases are hereditary. In the latter group, a syndrome which has been well characterised is hereditary diffuse gastric cancer; this is specifically associated with CDH1 (E-cadherin) germline mutations in about 30% of families. In this article, the state of the art of familial gastric cancer regarding the clinical, molecular and pathology features is reviewed, as well as the practical aspects for a correct diagnosis and clinical management.     

HtrA1, a potential predictor of response to cisplatin-based combination chemotherapy in gastric cancer

Catalano V, Mellone P, d’Avino A, Shridhar V, Staccioli M P, Graziano F, Giordani P, Rossi D, Baldelli A M, Alessandroni P, Santini D, Lorenzon L, Testa E, D’Emidio S, De Nictolis M, Muretto P, Fedeli S L & Baldi A
(2011) Histopathology 58 , 669–678
HtrA1, a potential predictor of response to cisplatin‐based combination chemotherapy in gastric cancer Aims: HtrA1 is a member of the HtrA (high‐temperature requirement factor A) family of serine proteases. HtrA1 plays a protective role in various malignancies due to its tumour suppressive properties. The aim of this study was to determine HtrA1 expression as a predictor of chemoresponse in patients with advanced gastric cancer. Methods and results: HtrA1 expression was determined by immunohistochemistry on specimens of primary gastric cancer from 80 patients treated consecutively with cisplatin‐based combination chemotherapy. Response to chemotherapy was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Our population consisted of males/females [51/29; median age 64 years (range 32–82)]. A complete or partial response was observed in 71.4% [95% confidence interval (CI) 54.7–88.2], 66.7% (95% CI 47.8–85.5) and 28.6% (95 CI 11.8–45.3) of tumours showing high, medium and low HtrA1 expression, respectively. A statistically significant association between HtrA1 expression and the clinical response was observed (P = 0.002). The median overall survival for patients with high/medium expression was 17 months compared to 9.5 months for patients with low HtrA1 expression (P = 0.037). Conclusions: Identification of HtrA1 in gastric cancer prior to chemotherapy indicates that levels of HtrA1 could be used to predict response to platinum‐based combination therapies. Further assessment of HtrA1 expression is highly warranted in large, prospective studies.     

多西他赛联合奥沙利铂应用于胃癌术前辅助化疗的临床疗效对比

胃癌为常见的恶性肿瘤,发病率仅次于肺癌。由于胃癌早期缺乏特殊征象,确诊时一半以上人群己属晚期,手术后5年生存率也仅30%～40%。因此,如何提高进展期胃癌的疗效是目前研究热点之一。本文采用多西他赛联合奥沙利铂用于胃癌术前辅助化疗,取得了满意效果,现报告如下。     

贝伐珠单抗联合化学药物治疗晚期胃癌的疗效观察

目的:贝伐珠单抗是血管内皮生长因子的重组人源化单克隆IgGI抗体,通过抑制肿瘤血管生成而发挥抗肿瘤作用.本研究旨在观察贝伐珠单抗联合化学药物治疗晚期胃癌的疗效与安全性.方法:12例晚期胃癌患者均经病理组织学确诊后接受贝伐珠单抗联合化学药物治疗.贝伐珠单抗的剂量为7.5 mg/kg,第1天给药,21d1个周期,每2个周期评价疗效.结果:12例患者均可评价疗效和毒副反应,一线治疗5例,二线治疗7例,根据实体瘤的疗效(response evaluation criteria in solid tumors,RECIST)评定标准,无完全缓解患者,部分缓解8例(66.7％),病情稳定3例(25.0％),病情进展1例(8.3％),客观有效率67％,疾病控制率91％.中位无进展生存时间5.5个月,中位总生存期7.0个月.骨髓抑制6例,肝损害3例,胃肠道反应2例,高血压1例,均为Ⅰ～Ⅱ度,经对症治疗后好转,无严重不良事件.结论:贝伐珠单抗联合化学药物治疗晚期胃癌临床疗效较好,用药期间不良反应可耐受.     

Undifferentiated leukemia following treatment of gastric cancer with 5 fluorouracil, doxorubicin, mitomycin C chemotherapy

Secondary leukemias are an increasingly well recognized complication of cancer chemotherapy. We report on the development of undifferentiated leukemia in a forty one year lady, eighteen months after treatment of gastric cancer with 5-fluorouracil (5 FU), doxorubicin and mitomycin C. She developed progressive weakness and pancytopenia over a period of few months. Leukemic blasts which were undifferentiated by immunophenotyping were seen in her peripheral blood. She died of intracranial haemorrhage during induction chemotherapy for the leukemia. Undifferentiated leukemia is a rare complication of FAM chemotherapy for gastric cancer.     

Adjuvant chemotherapy of breast cancer: Hope — Reality — Hazard?

Summary According to a NIH Consensus-Development Statement, adjuvant polychemotherapy following mastectomy is considered beneficial to premenopausal patients with positive axillary nodes. Nevertheless, the role of adjuvant chemotherapy in relation to menopausal status, axillary lymph node status, estrogen receptor status, choice and dose of agents, and long-term survival is not defined. Based on experimental background information and theoretical deductions, the clinical results have fallen short of expectations. The data of Bonadonna's CMF study reveal that the overall 5-year survival is increased by 4%; premenopausal patients benefit by 12% whereas treated postmenopausal patients have a 5% less chance of survival. Only those patients benefit who can tolerate a full or nearly full dose; these are only 17%. At this time it is not clear whether the small survival differences from adjuvant chemotherapy represent a real step forward in the fight against breast cancer. In the majority of patients (75 to 85%), at the time of adjuvant chemotherapy, systemically disseminated cancer cells are at mitotic rest or their proliferation is minimal. At this stage, adjuvant chemotherapy has no or little effect. Therefore, only a small proportion of patients (15 to 25%) has subclinical systemic cancer growth at the time of primary therapy or thereafter; only these patients have a chance to respond to chemotherapy. In view of this tumor kinetic problem and the hazards of chemotherapy, it seems advantageous (a) to focus on definition of patient subgroups at high risk for early recurrence post primary therapy to serve as participants in trials of adjuvant chemotherapy and/or (b) to concentrate on early diagnosis of recurrent disease for immediate institution of endocrine-and/or polychemotherapy.     

Update in cancer chemotherapy: genitourinary tract cancer, Part 1

An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series. Included in the review are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 1 focuses on the kidney.     

Update in cancer chemotherapy: gastrointestinal cancer--colorectal cancer, Part 1

An update of the state of the art of cancer chemotherapeutic treatment of gastrointestinal tract cancer is described. A review of cancers of the colon, rectum, anus, pancreas, stomach, small intestine, biliary passages, liver, and esophagus will be published in a multiple-part series. Part 1 will survey colorectal cancer and the use of single-agent chemotherapy.