The combination of docetaxel and cisplatin plus fluorouracil as neoadjuvant chemotherapy in the treatment of T4 stage gastric cancer

The prognosis of local advanced gastric carcinoma is very poor. We evaluated the impact on survival and the effects induced by the triple combination docetaxel–cisplatin–fluorouracil (DCF) as neoadjuvant chemotherapy in 24 T4 stage gastric tumor patients. They received 2–3 cycles DCF chemotherapy, followed by radical gastric resection. Tumor downstaging detected by CT was obtained in 17 out of 24 patients. The overall 3-year survival rate was 68.2%. Patients who received R0 resection (19/22) showed a 3-year survival rate of 78.9%. T downstaged patients (17/22) showed a higher 3-year survival rate of 82.4%. Those who responded to the triple combination of docetaxel–cisplatin–fluorouracil, exhibited T downstaging and subsequently received an R0 resection had a definitely better chance of a cure as compared to surgery alone, according to a complete 3-year follow-up.     

Weekly docetaxel and cisplatin with concomitant radiotherapy in addition to surgery and/or consolidation chemotherapy in stage III non-small cell lung cancer

Purpose  

The aim of this study was to evaluate efficacy and feasibility of a combination of weekly docetaxel and cisplatin administered concomitantly with radiotherapy followed by surgery in addition to consolidation chemotherapy with docetaxel and cisplatin administered every 3 weeks in stage III non-small cell lung cancer (NSCLC).     

Adding docetaxel to cisplatin and fluorouracil in patients with unresectable head and neck cancer: a cost-utility analysis

BackgroundAdding docetaxel (Taxotere, T) to induction chemotherapy with platinum/infusional 5-FU (PF) has been shown to improve overall survival of patients with head and neck cancer. The aim of the study was to analyze the cost–utility of TPF in patients with unresectable disease.DesignWe developed a Markov model to represent patient's weekly transitions among different health states, related to treatment or disease status. Transition probabilities were obtained from the TAX 324 clinical trial report and from the European Organization for Research and Treatment of Cancer (EORTC) 24971/TAX 323 raw data. Costs were estimated in Italy from a Regional Healthcare System perspective. A 5-year temporal horizon was adopted and a 3.5% yearly discount rate was applied.ResultsWhen compared with PF, TPF treatment increases life expectancy by 0.33 quality-adjusted life-years (QALYs) in TAX 323 and 0.41 QALYs in TAX 324. The benefit was achieved at a cost of €11 822/QALY for TAX 323 and €6757/QALY for TAX 324. Monte Carlo sensitivity analysis showed that 69% (TAX 323) and 99% (TAX 324) of the results lie below the threshold of €50 000/QALY saved.ConclusionsIn our analysis, TPF induction chemotherapy proved to be cost-effective when compared with PF, having a cost–utility ratio comparable to other widely accepted healthcare interventions.     

多西他赛联合顺铂、氟尿嘧啶和亚叶酸的新辅助化疗方案治疗不能切除进展期胃癌的疗效观察

背景与目的：手术治疗目前仍是无远处转移胃癌的标准治疗方法，但大多数胃癌患者就诊时已经是进展期而不宜手术。新辅助化疗足指在外科手术术前给予化疗，其目的之一是通过缩小原发肿瘤使之可以进行手术切除，最终延长生存期。本临床试验目的在于研究多西他赛（商品名：泰索帝）联合顺铂、氟尿嘧啶和亚叶酸给药方案术前进行诱导化疗对不能切除的进展期胃癌的临床疗效及毒副反应。方法：入组患者均为本院2003年6月-2005年6月收治的12例晚期胃癌而无法行根治手术者。术前的新辅助化疗方案为：泰索帝75mg／m^2、顺铂75mg/m^2。第1天；氟尿嘧啶500mg／m^2、亚叶酸200mg／m^2第1～5天，每三周为一个周期，共两个周期。观察新辅助化疗后原发病灶的变化情况并观察用药后的毒副反应。结果：新辅助化疗后9例患者获得肿瘤减期，疗程结束后4～6周8例进行根治性手术切除。临床完全缓解（CR）1例，部分缓解（PR）8例，无变化（NC）3例，进展（PD）0例，有效率75％（9／12），腹水消退率63.6％（7／11）。组织学效果：轻度有效3例，中度有效4例，显著有效1例。副反应主要为骨髓抑制、腹泻、恶心呕吐、脱发，经对症以及营养支持治疗后均能缓解。结论：多西他赛加顺铂、氟尿嘧啶及亚叶酸的新辅助化疗方案在高度进展期胃癌的治疗中，对提高手术切除率疗效显著，耐受性良好。     

Validity of neoadjuvant chemotherapy with docetaxel,cisplatin, and S-1 for resectable locally advanced gastric cancer

Gastrectomy with D2 lymphadenectomy plus postoperative chemotherapy is the standard treatment for resectable locally advanced gastric cancer in Japan. However, the prognosis of patients with serosa-positive tumors remains unsatisfactory because of peritoneal recurrence. This study aimed to investigate the validity of neoadjuvant therapy with docetaxel, cisplatin, and S-1 (DCS) in patients with locally advanced gastric cancer. Thirty patients with locally advanced gastric cancer underwent neoadjuvant DCS therapy at Dokkyo Medical University Hospital between June 2013 and October 2015. Gastrectomy and D2 lymphadenectomy were performed after two cycles of preoperative DCS therapy. The clinical responses of the primary gastric tumors based on endoscopic findings were partial response in 17 patients (57%) and stable disease in 13 patients (43%). Analysis of pathological response in the primary gastric lesions showed grade 1a in five patients (17%), grade 1b in nine patients (30%), grade 2 in 11 patients (37%), and grade 3 in five patients (17%). Twenty-four patients (80%) remained alive after a median follow-up period of 31 months. The 2- and 3-year overall survival rates in all patients were 89 and 70%, respectively. The 2-year overall survival rate in pathological responders (grade 1b-3) was 96%, compared with 50% in pathological non-responders (grade 1a) (P = 0.00187). Pathological responders had a significantly higher survival rate than non-responders. These results indicate that neoadjuvant DCS therapy may improve the prognosis in patients with serosa-positive locally advanced gastric cancer.     

顺铂联合氟尿嘧啶与顺铂联合多西他赛治疗局部晚期食管鳞状细胞癌的临床疗效

目的探讨顺铂联合氟尿嘧啶与顺铂联合多西他赛治疗局部晚期食管鳞状细胞癌的临床疗效、不良反应及对患者生活质量的影响。方法根据治疗方法的不同将86例局部晚期食管鳞状细胞癌患者分为对照组和观察组,每组43例,观察组患者采用顺铂联合多西他赛治疗,对照组患者采用顺铂联合氟尿嘧啶治疗。化疗完成3周后,对两组患者的临床疗效、不良反应、生活质量及治疗前后的血清癌胚抗原(CEA)和鳞状上皮细胞癌抗原(SCC-Ag)水平进行比较。结果观察组患者的总有效率为81.40%,高于对照组的65.12%,差异有统计学意义(P<0.05)。治疗后观察组患者的生活质量改善率为88.37%,高于对照组的65.12%(P<0.05)。观察组患者静脉炎、骨髓抑制、恶心呕吐的发生率均低于对照组(P<0.05)。治疗后两组患者的CEA、SCC-Ag水平均低于本组治疗前,且观察组患者的CEA、SCC-Ag水平均低于对照组,差异均有统计学意义(P<0.05)。结论与顺铂联合氟尿嘧啶方案相比,顺铂联合多西他赛治疗局部晚期食管鳞状细胞癌的临床疗效较好,不良反应发生率较低,患者耐受性较高,并可在一定程度上提高患者的生活质量,是治疗局部晚期食管鳞状细胞癌的可选方案。     

多西他赛、氟脲嘧啶分别联合奥沙利铂或顺铂治疗进展期胃癌的临床对照观察

目的评价多西他赛联合奥沙利铂、氟脲嘧啶（DOF方案）与多西他赛联合顺铂、氟脲嘧啶（DCF方案）组成的5d联合方案一线治疗进展期胃癌的有效性和安全性。方法75例病人分为A,B两组。A组38例,接受DOF方案治疗。DOF方案：多西他赛75mg／m^2,d2,奥沙利铂130mg／m^2,d1,氟脲嘧啶500mg／m2,d1-d5;B组37例,接受DCF方案治疗。DCF方案：多西他赛75mg／m^2,d2,顺铂25mg／m^2,dl-d3,氟脲嘧啶500mg／m^2,dl-d5。均每3wk重复,至少应用2周期。结果A组病人临床控制率、完全缓解率、部分缓解、中位治疗至进展时间、中位生存期以及1a生存率和2a的生存率分别为65．78％、5．26％、42．10％、5．9mo、11．2mo、52．63％、18．42％。B组分别为54．06％、2．70％、35．14％、5．8mo、10．8mo、48．64％、13．51％。治疗前两组生活质量（QOL）分值相当,但是治疗后1mo、2mo的QOL分值似有差异,但两组有效率与生存期比较差异并无显著性（P〉0．05）。两组主要毒副反应为骨髓抑制、恶心呕吐,但不严重。结论多西他赛联合奥沙利铂、氟脲嘧啶和多西他赛联合顺铂、氟脲嘧啶一线治疗进展期胃癌疗效均确切、毒副反应均可以接受。与最好的支持治疗相比联合化疗可延长病人生存期,提高生活质量。特别是前者对生活质量的影响比后者轻。     

Weekly docetaxel and cisplatin plus fluorouracil as a preoperative treatment for gastric cancer patients with synchronous multiple hepatic metastases: a pilot study

This pilot study was undertaken to assess the effect of weekly docetaxel, cisplatin and fluorouracil (DCF) as a preoperative treatment for gastric cancer with multiple synchronous hepatic metastases. Gastric cancer patients with synchronous multiple liver metastasis were first given preoperative chemotherapy consisting of two courses (each course consisted of 6-week administration and 2-week withdrawal) of weekly DCF regimen. Following the operation, postoperative chemotherapy and hepatic arterial infusion (HAI) treatment were performed as required. Eight patients completed two courses of preoperative chemotherapy with weekly DCF regimen. No toxicity of grade 3 or more was observed during the course of chemotherapy. The response rate was 100% according to the RECIST criteria. Seven of the patients have survived for over 1 year, and six of them are still alive after more than 1 year. Because of the unexpected high response to weekly DCF, we consider that it should be verified through phase II and III trials as an important part of the comprehensive treatment for gastric cancer with liver metastasis.     

A propensity score-matched analysis of oncological outcome after systemic therapy for stage IV colorectal cancer: Impact of synchronous ovarian metastases

The reported incidence of synchronous and metachronous ovarian metastases (OM) from colorectal cancer (CRC) is ~3.4%. OM from CRC are often considered sanctuary sites due to their lower sensitivity to systemic treatment. It has thus been hypothesized that the presence of OM decreases overall survival. Therefore, the purpose of our study was to evaluate the impact of synchronous OM on overall survival in female patients with stage IV CRC treated with systemic therapy alone with palliative intent. The present study used data from the Netherlands Cancer Registry and included female CRC patients with synchronous systemic metastases who were treated with systemic therapy between 2008 and 2018. A subsample was created using propensity score matching to create comparable groups. Propensity scores were determined using a logistic regression model in which the dependent variable was the presence of OM and the independent variables were the variables that differed significantly between both groups. Our study included 5253 patients with stage IV CRC that received systemic therapy. Among these patients, 161 (3%) had OM while 5092 (97%) had extra-ovarian metastases only. Three-year overall survival rates did not show a significant difference between patients with OM compared to patients without ovarian metastases. Moreover, the propensity score-matched analysis showed that the presence of OM in patients treated with systemic therapy for stage IV CRC disease was not associated with decreased 3-year overall survival. However, the results of the present study should be interpreted with caution, due to its observational character and used selection criteria.     

多西他赛联合氟尿嘧啶、顺铂方案与多西他赛联合氟尿嘧啶、洛铂方案治疗胃癌的疗效比较

目的:比较多西他赛联合氟尿嘧啶、顺铂方案与多西他赛联合氟尿嘧啶、洛铂方案治疗晚期不可手术胃癌患者的疗效和不良反应。方法:回顾性分析2015年2月至2018年6月126例晚期不可手术的胃癌患者。洛铂组55例:多西他赛+氟尿嘧啶+洛铂,顺铂组71例:多西他赛+氟尿嘧啶+顺铂。洛铂组和顺铂组均21天为一个疗程,连续治疗四个疗程。结果:洛铂组患者客观有效率为50.91%,顺铂组为35.21%,差异无统计学意义（P＞0.05）。洛铂组患者疾病控制率达到83.64%,顺铂组为67.61%,差异有统计学意义（P＜0.05）。洛铂组患者在恶心、呕吐、白细胞减少和四肢麻木方面发生率明显低于顺铂组,差异有统计学意义（P＜0.05）。洛铂组患者血小板减少发生率高于顺铂组,差异有统计学意义（P＜0.05）。洛铂组患者严重不良反应的发生率为21.82%,顺铂组为39.44%,差异具有统计学意义（P＜0.05）。结论:将多西他赛联合氟尿嘧啶、顺铂方案中的顺铂以洛铂替代,取得了更好的疾病控制率,而患者的不良反应更轻,严重不良反应的发生率也更低,值得临床进一步研究。     

Early administration of pegfilgrastim for esophageal cancer treated with docetaxel,cisplatin, and fluorouracil: A phase II study

Preoperative or induction chemotherapy with docetaxel, cisplatin, plus 5‐fluorouracil (DCF) is a promising regimen for advanced esophageal cancer. However, the DCF regimen is associated with a high risk of severe neutropenia or febrile neutropenia (FN). However, the current guidelines fail to recommend an optimal dosing schedule of pegfilgrastim along with the DCF regimen to prevent FN. In the present study, we assessed the efficacy and safety of giving pegfilgrastim early on day 3 during DCF therapy for esophageal cancer. In this single‐arm phase II study, patients with squamous cell carcinoma of the esophagus were recruited. They were treated with the DCF therapy on days 1‐5, with pegfilgrastim given on day 3. Primary endpoint was the occurrence of grade 4 neutropenia. Secondary endpoints included the incidence of FN, grade 3 neutropenia, dose delays/reductions, antitumor effect, and safety. Between July 2016 and December 2018, 23 patients were enrolled. The incidence of grade 4 neutropenia was 8.7% (95% confidence interval 1.1%‐28.0%). No patient experienced FN. Of the 19 patients who received two cycles of DCF, one required a dose reduction/treatment delay due to hematological toxicity in the second treatment cycle. No serious adverse events, considered relevant to pegfilgrastim, were observed. This is the first prospective study that showed an efficacious dosing schedule of pegfilgrastim for preventing hematological toxicity during DCF therapy. The results might be generalized to other similar regimens where continuous infusions of 5‐fluorouracil are used.     

Multicenter randomized phase II study of cisplatin and fluorouracil plus docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as preoperative chemotherapy for resectable esophageal squamous cell carcinoma (OGSG1003)

BackgroundThis phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC.Patients and methodsPatients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35 mg/m², cisplatin 70 mg/m² i.v. on day 1, fluorouracil 700 mg/m² continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m², cisplatin 70 mg/m² i.v. on day 1, fluorouracil 700 mg/m² continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat.ResultsBetween October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33–0.83, P = 0.0057) and 78.6% versus 65.4% (P = 0.08), respectively.ConclusionCompared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC.Clinical Trial RegistrationUniversity Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).     

TPLF方案在局部进展期胃癌新辅助化疗中的应用

目的:研究泰索帝(多西紫杉醇,TAT)联合顺铂(CDDP)及氟尿嘧啶/亚叶酸钙(5-FU/CF)方案新辅助化疗(NCT)治疗局部进展期胃癌(LAGC)的疗效和毒副作用。方法:自2003年10月~2005年10月,有28例LAGC入组临床研究。入组病例术前接受TPLF化疗方案为:TAT(T)75mg/m2,第1天静滴;CDDP(P)30mg/m2,第1~3天静滴;5-FU(F)500mg/m2,第1~5天静滴;CF(L)100mg于5-FU前30分钟静脉冲入,每3周为1周期,共3个周期。观察新辅助化疗后肿瘤原发病灶的缓解情况、手术后病理缓解情况以及新辅助化疗的毒副反应。结果:新辅助化疗后所有患者进行了根治性手术治疗,临床有效率RR(CR PR)为57·1%(16/28),其中CR17·9%(5例),PR39·3%(11例),SD21·4%(6例),PD21·4%(6例),术后4例病理水平达到完全缓解(pCR),缓解率为14·3%(4/28)。毒副反应主要为白细胞减少、恶心、脱发、呕吐及粘膜炎,其中Ⅲ~Ⅳ级的白细胞减少共6例(21·4%),未发生严重感染和死亡病例。结论:TPLF方案新辅助化疗在LAGC的治疗中近期疗效显著,耐受性良好。     

Taxane-based chemotherapy enhances response to neoadjuvant treatment for stage II and III breast cancer

Reducing primary tumor volume is the main role of neoadjuvant chemotherapy for breast cancer. We evaluated the benefit of adding docetaxel to anthracyclin as neoadjuvant therapy. This study is a retrospective cohort analysis comparing the efficacy of neoadjuvant chemotherapy in patients subjected to docetaxel and epirubicin or 5-fluoruracil, epirubicin and cyclophosphamide combinations (DE and FEC group, respectively). The mean number of chemotherapy delivered was similar in both groups (P = 0.8). A total of 316 patients were treated (151 in FEC group and 165 in DE group). Primary endpoint was the clinical and pathological response to therapy. Breast conserving surgery rate was compared. In T1/2 staged patients, the complete clinical response rate was 7.5% in FEC group and 32% in DE group (P = 0.002), and the breast conserving surgery rate was 72 and 73% in FEC and DE groups, respectively (P = 0.9). In the subset of patients staged as T3 and T4a-c, objective response was higher in DE group (P < 0.0001 and P = 0.008, respectively). Breast conserving surgery rate was 38 and 63% in FEC and DE groups, respectively, in T3 staged patients and, 20.5 and 37% in T4a-c staged patients (P = 0.003 and 0.08). Despite the similar number of chemotherapy cycles delivered in both groups, the presence of microscopic axillary lymph node involvement after chemotherapy was less frequent in DE group. Neoadjuvant chemotherapy with DE combination is more effective in terms of clinical and pathological response propitiating higher breast conserving surgery rate than FEC combination in stage II and III breast cancer.     

Taxane-based chemotherapy enhances response to neoadjuvant treatment for stage II and III breast cancer

The feasibility, safety, and efficacy of planned sequential administration of docetaxel and irinotecan with 5-fluorouracil (5-FU)/leucovorin in advanced upper gastrointestinal adenocarcinoma (UGIA) are unknown. Seventy-three patients with gastric (GC; n = 22), pancreatic (PC; n = 28) or biliary cancer (BC; n = 23) were randomised to start with 45 mg/m² docetaxel or 180 mg/m² irinotecan combined with 5-FU/leucovorin every 2nd week. After every 2nd course, the patients were crossed over to the other combination. Treatment was given for a maximum of 12 courses. Quality-of-life (QoL) was evaluated during the first two months using the EORTC QLQ-C30. Eighteen patients (25%; GC 32%, PC 21%, BC 22%) demonstrated partial response (PR) and 21 (29%) had prolonged stable disease. Mean QoL scores were low at baseline. Twenty-three (32%) patients had improved QoL using a summary measure and 13 were stable. Median time to progression was 4.4 months and overall survival 8.2 months. The treatments were reasonably well tolerated. Grade 3–4 toxicities were slightly more common for the docetaxel combination. There were two treatment-related deaths. Planned sequential treatment with docetaxel or irinotecan with 5-FU/leucovorin is feasible, reasonably tolerable and appears active in advanced UGIA.     

Taxane-based chemotherapy enhances response to neoadjuvant treatment for stage II and III breast cancer

Reducing primary tumor volume is the main role of neoadjuvant chemotherapy for breast cancer. We evaluated the benefit of adding docetaxel to anthracyclin as neoadjuvant therapy. This study is a retrospective cohort analysis comparing the efficacy of neoadjuvant chemotherapy in patients subjected to docetaxel and epirubicin or 5-fluoruracil, epirubicin and cyclophosphamide combinations (DE and FEC group, respectively). The mean number of chemotherapy delivered was similar in both groups (P = 0.8). A total of 316 patients were treated (151 in FEC group and 165 in DE group). Primary endpoint was the clinical and pathological response to therapy. Breast conserving surgery rate was compared. In T1/2 staged patients, the complete clinical response rate was 7.5% in FEC group and 32% in DE group (P = 0.002), and the breast conserving surgery rate was 72 and 73% in FEC and DE groups, respectively (P = 0.9). In the subset of patients staged as T3 and T4a-c, objective response was higher in DE group (P < 0.0001 and P = 0.008, respectively). Breast conserving surgery rate was 38 and 63% in FEC and DE groups, respectively, in T3 staged patients and, 20.5 and 37% in T4a-c staged patients (P = 0.003 and 0.08). Despite the similar number of chemotherapy cycles delivered in both groups, the presence of microscopic axillary lymph node involvement after chemotherapy was less frequent in DE group. Neoadjuvant chemotherapy with DE combination is more effective in terms of clinical and pathological response propitiating higher breast conserving surgery rate than FEC combination in stage II and III breast cancer.