Split-dose docetaxel, cisplatin and leucovorin/fluorouracil as first-line therapy in advanced gastric cancer and adenocarcinoma of the gastroesophageal junction: results of a phase II trial.

BACKGROUND: Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but high rates of hematologic toxicity in advanced gastric cancer. To reduce toxicity while maintaining the efficacy of DCF, we investigated split doses of docetaxel (T), cisplatin (P), leucovorin (L) and fluorouracil (F). PATIENTS AND METHODS: Chemotherapy-naive patients with advanced gastric-/esophageal adenocarcinomas received T 50 mg/m(2) and P 50 mg/m(2) on days 1, 15 and 29 and L 500 mg/m(2) plus F 2000 mg/m(2) weekly, every 8 weeks. Because significant dose reductions to <80% became necessary in 80% of patients, the regimen was amended after the first 15 patients to T 40 mg/m(2), P 40 mg/m(2), L 200 mg/m(2) and F 2000 mg/m(2). The primary endpoint was response rate. RESULTS: Sixty patients were enrolled: 24 had locally advanced (LA) tumors and 36 had metastatic disease. Grade 3/4 toxicities included neutropenia (22%), febrile neutropenia (5%), diarrhea (20%) and lethargy (18%). The overall response rate was 47%. Twenty-three LA patients underwent secondary surgical resection (96%); complete resection was achieved in 87%. Overall, median time to progression and overall survival were 9.4 and 17.9 months, respectively (8.1 and 15.1 months, respectively, for patients with metastatic disease). CONCLUSION: T-PLF regimen is highly active and has a favorable toxicity profile.     

Sequential chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil in patients with locally advanced head and neck cancer

The purpose of this phase II trial was to evaluate the toxicity of a sequential chemoradiotherapy approach using docetaxel, cisplatin, and 5-fluorouracil (5-FU) (DCF) with granulocyte colony-stimulating factor support in previously untreated patients with locally advanced head and neck cancer (HNC). Secondary endpoints included preliminary assessment of response. Patients with locally advanced HNC, a World Health Organization performance status 0 to 2, and no prior history of chemotherapy or radiotherapy were included. Treatment consisted of docetaxel 80 mg/m2 (1-hour infusion) on day 1, cisplatin 40 mg/m2 (1-hour infusion) on days 2 and 3, and 5-fluorouracil 1,000 mg/m2 (24-hour continuous infusion), on days 1 to 3, repeated every 28 days for a maximum of 4 cycles per patient. All patients received granulocyte colony stimulating factors subcutaneously between days 4 and 9. Radiation therapy (RT) to the primary tumor site and neck lymph nodes was planned within 5 weeks of the last cycle of chemotherapy. The primary tumor site received 60 to 70 Gy. Twenty patients (median age 56 years, range: 40-72 years) received a total of 60 cycles of DCF. The median number of cycles was 3 (range: 1-4 cycles). All patients were evaluable for toxicity and response. The most common acute nonhematologic toxicities from DCF induction chemotherapy included alopecia, mucositis, peripheral sensory neuropathy, onycholysis, and asthenia. Febrile neutropenia developed in two patients and grade IV diarrhea in one patient. There were no treatment-related deaths. The overall response rate (RR) after DCF induction chemotherapy was 90% (95% confidence interval [CI]: 76.8-103.1%). After the completion of RT, the overall RR was 95% with a complete response rate of 73% (95% CI: 49.9-90.1%). Organ preservation was achieved in eight patients with laryngeal cancer and one patient with base of tongue involvement. After a median follow-up of 36 months (range: 5-43 months) the median disease-free and overall survival have not been reached yet. The 1- and 2-year survival rates were 85% and 60%, respectively. Sequential chemoradiotherapy with DCF and growth factor support is feasible and very active, with durable responses in patients with locally advanced head and neck cancer. Further evaluation of this modality is justified in the context of a clinical trial.     

Low-Dose Docetaxel/Cisplatin - Leucovorin and 46 Hour Infusional Fluorouracil in Metastatic Gastric Carcinoma

Background: Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superiorefficacy versus cisplatin and fluorouracil alone but with high rates of hematologic toxicity in metastatic gastriccancer cases. To reduce toxicity while maintaining the efficacy of DCF, we investigated low dose docetaxel (D),cispatin (C) - leucovorin and fluorouracil (De Gramont regimen). Patient and methods: Chemotherapy-naïvepatients with metastatic gastric cancer (MGC) received D 60 mg/m2 on day 1 and cisplatin 30 mg/m2 on day 1-2and the De Gramont regimen (Folinic acid 400 mg/m2 on day 1 and 5-FU 2400 mg/m2/46h continuous infusion)every 3 weeks. The primary endpoint was response rate. Results: One hundred twenty patients with a medianage of 52.5 years (range, 32-78) received a median of 6 cycles (range, 2-12 cycles). Of the 120 evaluable patients,4 showed complete remission and 36 achieved a partial response. The overall response rate was 56.6%. Twentyeight patients (23.3%) showed stable disease and 52 (43.3%) progression. The median time to progression was7 months (95%CI 6-7.9). The median overall survival was 15 months (95%CI 13.7-16.2). The most frequenthematological toxicity was leucopenia, which occurred at grade ¾ intensity in 24 patients (20%). Conclusions:Low-dose DC- De Gramont regimen is active in MGC with a tolerable toxicity profile.     

Modified Docetaxel and Cisplatin in Combination with Capecitabine (DCX) as a First-Line Treatment in HER2-Negative Advanced Gastric Cancer

Background: Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be oneof the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limitedits use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabinehas been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimenwith a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated inuntreated patients with HER2-negative advanced gastric cancer. Materials and Methods: Fifty-four patientswith HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients receiveddocetaxel 60 mg/m2 plus cisplatin 60 mg/m2 (day 1) combined with capecitabine 1650 mg/m2 (days 1–14) every3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. Results: The median age was54 years (range: 24–76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) hadrecurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD).The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with anoverall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. Atthe median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of theentire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients dueto toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia,which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only intwo cases. Conclusions: DCX regimen offers prominent anti-tumor activity and considered to be effective firstlinetreatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.     

A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas.

BACKGROUND AND PURPOSE: This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. MATERIAL AND METHODS: A total of 94 patients (median age, 58 years) with UICC stage III (n = 19) and IV (n = 75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m(2) weekly, for the first 4 weeks. RESULTS: Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. CONCLUSIONS: Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data.     

Epirubicin, cisplatin, and raltitrexed in patients with advanced gastric and hepatobiliary carcinoma: a phase II study

The combination of epirubicin, cisplatin, and protracted venous-infusion 5-fluorouracil is the standard treatment of advanced gastric carcinoma in many European countries, and it is also an active regimen in hepatobiliary tumors. Raltitrexed is a specific inhibitor of thymidylate synthase with clinical activity in gastrointestinal malignancies. The aim of the study was to evaluate the clinical activity and toxicity of the combination of epirubicin, cisplatin, and raltitrexed in patients with advanced gastric and hepatobiliary tumors. Twenty consecutive patients with gastric carcinoma, 7 with biliary-tract carcinoma, and 5 patients with hepatocarcinoma were treated with epirubicin (60 mg/m2), cisplatin (60 mg/m2) on day 1, and raltitrexed (1 mg/m2) on days 1 and 8, every 3 weeks. The median age was 63 years (range, 28-76). Eight patients had locally advanced disease and 24 had metastatic tumors. Seven of the 18 evaluable patients (39%) with gastric carcinoma and 2 of the 5 patients with hepatocarcinoma have a partial response; 1 minimal response and 4 stabilization of disease were documented in the 7 patients with biliary-tract carcinoma. The median time to progression of the entire group was 6.8 months, and the median survival was 9.0 months. The toxicity was mild and no toxic death occurred. The combination of epirubicin, cisplatin, and raltitrexed, using this schedule, is tolerable and has clinical activity in gastric and hepatobiliary tumors.     

Lack of effectiveness of radiotherapy combined with cisplatin in patients with locally advanced pancreatic carcinoma

BACKGROUND: Cisplatin has been reported to enhance the cell-killing effect of radiation. The current study was conducted to evaluate the efficacy and toxicity of radiotherapy combined with cisplatin in patients with locally advanced pancreatic carcinoma. METHODS: Forty-one patients with pancreatic carcinoma that was unresectable but confined to the pancreatic region were treated with external beam radiation (50.4 grays [Gy] in 28 fractions over 5.5 weeks) and daily cisplatin (5 mg/m(2)/day as a 30-minute infusion just before each radiation fraction). Maintenance 5-fluorouracil (5-FU) (500 mg/m(2)) given once weekly was initiated 1 week after the completion of the chemoradiotherapy and continued until disease progression or unacceptable toxicity. RESULTS: Of the 41 patients, 31 (76%) completed the scheduled course of chemoradiotherapy. The median survival time was 7.7 months, and the 1-year survival rate was 36%. The median progression free survival time was 5.8 months. The first site of failure was distant metastases in 25 patients, locoregional recurrence in 6 patients, and both sites in 1 patient. The major toxicity was leukocytopenia and nausea/emesis. CONCLUSIONS: Radiotherapy with daily cisplatin appears to be inferior to conventional chemoradiotherapy using 5-FU in patients with locally advanced pancreatic carcinoma.     

A phase II study of mitomycin C, cisplatin and protracted infusional 5-fluorouracil in advanced pancreatic carcinoma: efficacy and low toxicity.

BACKGROUND: The effective treatment of unresectable pancreatic carcinoma represents a formidable challenge. There is a need to develop systemic therapies which combine efficacy with acceptable toxicity. The current 'gold standard' gemcitabine gives an objective response rate of the order of 20% and median survival up to 6 months. Here we have evaluated the efficacy and toxicity of mitomycin C, cisplatin and protracted infusional 5-fluorouracil (MCF). PATIENTS AND METHODS: Forty-five patients with locally advanced (13 patients) or metastatic (32 patients) pancreatic carcinoma were treated with mitomycin C 7 mg/m(2) 6 weekly, cisplatin 60 mg/m(2) 3 weekly and protracted venous infusion 5-FU 300 mg/m(2)/day. Patients were evaluated for response after three cycles and received six cycles in total in the absence of progressive disease or poor tolerance. Median age was 62 (45-75) years; 41 patients were World Health Organization performance status 0-1. RESULTS: Treatment was well tolerated with 36 (84%) patients completing three or more cycles. Grade 3 or 4 toxicities were uncommon: anaemia in three patients (7%), mucositis in two (5%), nausea and vomiting in three (7%) and diarrhoea in one (1%). An objective response was seen in 21 (46%) patients. There was one complete response. The median survival overall was 7.1 months and 10.5 months in responders. The median duration of response was 4.3 months. One-year survival was 29%, 2-year survival was 18%. CONCLUSIONS: MCF combines efficacy with low toxicity in the treatment of advanced pancreatic carcinoma. The efficacy is at least comparable and may be superior to single-agent gemcitabine and MCF may therefore provide a cost-effective alternative.     

Outpatient therapy with irinotecan and low-dose cisplatin for metastatic colorectal cancer resistant to 5-fluorouracil

Chemotherapy with irinotecan hydrochloride and low-dose cisplatin was tested for the treatment of metastatic colorectal cancer showing resistance to 5-fluorouracil. Eleven consecutive patients with advanced metastatic colorectal cancer (performance status: 0 to 2), who had shown tumor progression on chemotherapy with 5-fluorouracil/leucovorin, were treated with irinotecan (60 mg/m2) plus cisplatin (6 mg/m2) by 90-min intravenous infusion. Treatment was repeated weekly for 3 weeks during admission and then fortnightly on an outpatient basis. Objective responses were observed in four patients (36%; 95% confidence interval: 11%-69%). The median duration of response was 5.5 months and six patients are still alive. The time to disease progression was longer in the no change group (7.0+/-3.6 months: mean +/- SD) than in the responder group (5.5+/-1.9 months), and there was no difference of median survival between the two groups (10.0 versus 10.3 months). The overall median survival was 8.2 months (range: 4 to 12+ months). This treatment was well tolerated. Six patients experienced grade 1 or 2 leucopenia, while grade I diarrhea and nausea occurred in three and five patients, respectively. Based on the good response, excellent quality of life, and convenience, the present regimen seems to be reasonable second-line outpatient chemotherapy for patients with metastatic colorectal cancer showing resistance to 5-fluorouracil.     

Combination chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in previously treated patients with advanced/recurrent head and neck cancer: a phase II feasibility study

The purpose of this phase II feasibility trial was to determine the efficacy and toxicity of docetaxel combined with cisplatin and 5-fluorouracil in patients with locally advanced and/or recurrent squamous cell carcinoma of the head and neck. Nineteen patients entered the study. The majority had received prior radiotherapy but were chemotherapy naive. Treatment consisted of docetaxel 80 mg/m2 day 1, cisplatin 40 mg/m2 days 2 and 3, and 5-fluorouracil 1,000 mg/m2 by continuous infusion days 1 to 3. The cycle was repeated every 28 days. Most patients received granulocyte colony-stimulating factor, 150 microg/m2/day subcutaneously between days 4 and 8. The median number of chemotherapy cycles per patient was four. Dose reduction was done in three patients with no treatment delays. Of the 16 evaluable for response, seven patients (44%) demonstrated an objective response, including two complete and five partial ones; eight patients (50%) had stable disease; and one patient had progressive disease. The median time to progression was 7.5 months (range: 4-17.5 months). The median survival was 11 months (range: 1-18 months) and 1-year survival was 49%. Febrile neutropenia was recorded in 15% of courses. There were no toxic deaths. In conclusion, the combination of docetaxel, cisplatin, and 5-fluorouracil is an active regimen against previously treated squamous cell carcinoma of the head and neck with acceptable toxicity.     

TCF方案与PF方案治疗晚期食管癌的临床研究

目的:观察比较紫杉醇联合顺铂、氟尿嘧啶(TCF方案)与顺铂加氟尿嘧啶(PF方案)两个方案治疗晚期食管癌的临床疗效和毒性反应。方法:共69例患者,分别用TCF、PF方案化疗,28天为1个周期。2个周期以后按照WHO标准进行疗效评价。结果:TCF方案可评价疗效者32例,CR2例,PR15例,有效率53.1%。中位疾病进展时间为5.4个月,中位生存时间10.1个月。可评价毒副反应33例。主要不良反应为脱发、中性粒细胞降低,恶心、呕吐也较常见。PF方案可评价疗效者29例,PR14例,有效率48.3%。中位疾病进展时间3.9个月,中位生存期8.7个月。主要不良反应为恶心、呕吐。结论:TCF方案对晚期食管癌疗效好,毒副反应可耐受,可以考虑作为治疗晚期食管癌的主要治疗方案。     

A phase II trial of continuous infusion of 5-fluorouracil, mitoxantrone, and cisplatin for metastatic hepatocellular carcinoma

BACKGROUND: The aim of the current study was to evaluate the antitumor activity and toxicity of continuous infusion of 5-fluorouracil, mitoxantrone, and cisplatin (FMP therapy) in chemotherapy-naive patients with metastatic hepatocellular carcinoma (HCC). METHODS: Fifty-one patients with metastatic HCC who had not undergone previous systemic chemotherapy were enrolled. The therapy consisted of intravenous administration of 80 mg/m2 cisplatin and 6 mg/m2 mitoxantrone on Day 1 and continuous intravenous infusion of 450 mg/m2 5-fluorouracil per day on Days 1-5. The treatment was repeated every 4 weeks for a maximum of 6 courses with dose adjustments based on the observed toxic effects if there was no evidence of tumor progression or unacceptable toxicity. RESULTS: Of the 51 enrolled patients, 14 (27%) achieved a partial response (95% confidence interval, 16-42%) with a median duration of 7.6 months (range, 2.3-18.4 months). Twenty-seven patients (53%) showed no change and 9 (18%) had progressive disease. The median survival time, 1-year survival rate, and median progression-free survival time for all patients were 11.6 months, 44.3%, and 4.0 months, respectively. The main Grade 3 and 4 toxicities were leukocytopenia (67%), neutropenia (71%), thrombocytopenia (27%), and elevated levels of aspartate aminotransferase (37%) and alanine aminotransferase (41%). These symptoms were generally brief and reversible, with the exception of one treatment-related death due to acute hepatic failure. CONCLUSIONS: FMP therapy had significant antitumor activity with acceptable toxicity in patients with metastatic HCC.     

DCF方案与OLF方案治疗晚期胃癌的临床观察

目的观察DCF方案和OLF方案治疗晚期胃癌的临床疗效和不良反应。方法 92例晚期胃癌患者随机分为2组,其中DCF组43例,OLF组49例。DCF方案:多烯紫杉醇35 mg/m2,静脉滴注,第1天及第8天;顺铂25 mg/m2,静脉滴注第2～4天;5-氟尿嘧啶500 mg/m2,持续静脉泵入,第1～5天,3周为1个周期。OLF方案:奥沙利铂130mg/m2,静脉滴注3 h,第1天;亚叶酸钙200 mg/m2,静脉滴注第1～5天;5-氟尿嘧啶500 mg/m2在亚叶酸钙后静脉滴注3 h,第1～5天,3周为1个周期。2组均治疗2个周期以上,按WHO标准评价客观疗效和不良反应。结果入组的92例患者均可评价疗效,DCF组有效率46.5%,中位进展时间为6.8个月,中位生存时间11.4个月;OLF组有效率32.7%,中位进展时间为5.1个月,中位生存时间10.1个月。不良反应中外周神经炎的发生率以OLF组显著(P<0.05),其余不良反应发生率差异无统计学意义。结论 DCF方案与OLF方案治疗晚期胃癌疗效确切,其中以DCF方案疗效略高,不良反应均能耐受。     

Preoperative docetaxel/cisplatin/5-fluorouracil chemotherapy in patients with locally advanced gastro-esophageal adenocarcinoma

Perioperative chemotherapy plus surgery improves survival compared to surgery alone in GE junctional (GEJ) and gastric adenocarcinomas. The docetaxel/cisplatin/5-fluorouracil (DCF) combination is superior to CF in patients with metastatic gastric cancer. We retrospectively evaluated the safety and efficacy of preoperative DCF chemotherapy in patients with locally advanced gastric and GEJ cancer. Twenty-one gastric and 10 gastroesophageal junctional (GEJ) cancer patients received 2-3 cycles of preoperative docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, 5-FU 750 mg/m(2) (continuous infusion) on days 1-5 every 3 weeks. Clinical response was evaluated by comparing pre- and postchemotherapy CT scans. Overall survival (OS) and progression-free survival (PFS) were calculated from the initiation of chemotherapy. None of the patients achieved complete clinical remission while 11 (35%) patients achieved partial clinical remission. Ten patients with GEJ cancer (100%) and 13 with gastric cancer (62%) underwent curative surgery (P = 0.023). Seventeen (55%) patients experienced grade 3-4 chemotherapy-related adverse events. The most common adverse events were anemia, nausea/vomiting, diarrhea, and febrile neutropenia. At a median follow-up of 17.0 months, median OS and PFS were 26.1 months (95% CI: 22.7-29.5) and 18.8 months (95% CI: 9.9-27.7), respectively. The DCF regimen is active in patients with gastric and GEJ adenocarcinoma in the preoperative setting.     

周剂量多西紫杉醇联合顺铂、氟尿嘧啶二线治疗晚期胃癌32例

[目的]研究周剂量多西紫杉醇（TXT）联合顺铂（DDP）、氟尿嘧啶（5-Fu）持续滴注二线治疗晚期胃癌的疗效和不良反应。[方法]32例晚期胃癌患者接受DCF方案二线化疗：TXT30mg/m2,d1,8,15,DDP25mg/m2,d1～3,5-Fu500mg/m2持续静脉滴注,d1～5,28d为1个周期。至少完成2个周期后评价有效率、不良反应、疾病进展时间（TTP）和总生存时间（OS）。[结果]32例患者均可评价疗效,客观缓解率21.9%（7/32）,中位TTP及OS分别为2.7个月和7.6个月。主要不良反应为骨髓抑制、胃肠道反应和脱发。[结论]周剂量TXT联合DDP、5-Fu持续滴注二线治疗晚期胃癌疗效显著,不良反应可以耐受。     

Phase II study of continuous infusional 5-fluorouracil with epirubicin and carboplatin (instead of cisplatin) in patients with metastatic/locally advanced breast cancer (infusional ECarboF): a very active and well-tolerated outpatient regimen.

Infusional 5-fluorouracil (F) with cisplatin (C) and epirubicin (E), so-called infusional ECF, is a highly active new schedule against locally advanced or metastatic breast cancer. Cisplatin, however, is a major contributor to toxicity and usually requires inpatient treatment. In an attempt to overcome this, we have investigated the effect of substituting carboplatin for cisplatin in our original infusional ECF regimen. Fifty-two patients with metastatic (n = 36) or locally advanced/inflammatory (n = 16) breast cancer were treated with 5-fluorouracil 200 mg m-2 day-1 via a Hickman line using an ambulatory pump for for 6 months, with epirubicin 50 mg m-2 intravenously (i.v.) and carboplatin AUC5 i.v. every 4 weeks, for six courses (infusional ECarboF). The overall response rate (complete plus partial) was 81% (95% CI 67%-90%), with a complete response rate of 17% (95% CI 6-33%) in patients with metastatic disease and 56% (95% CI 30-80%) in patients with locally advanced disease. Median response duration and survival for metastatic disease was 8 and 14 months respectively, and two patients with locally advanced disease have relapsed. These results are very similar to those previously achieved with infusional ECF. Severe grade 3/4 toxicity was low. Infusional ECarboF is a highly active, well-tolerated, outpatient regimen effective against advanced/metastatic breast cancer and now warrants evaluation against conventional chemotherapy in high-risk early breast cancer.     

晚期胃癌DCF方案与ECF方案治疗的Meta分析

目的 比较DCF方案（多西他赛、顺铂和5-Fu）与ECF（表阿霉素、顺铂和5-Fu）方案治疗晚期胃癌的有效性与安全性。方法 计算机检索PubMed、CNKI、CBM 、Medalink和万方数据库以及Google学术搜索、手工检索,查找所有比较DCF方案与ECF方案治疗晚期胃癌疗效的随机对照实验(RCT),依据 Cochrane Handbook 5.0.1 的质量评价标准进行RCT筛选、资料提取和质量评价后,按Cochrane 协作网推荐的方法使用RevMan 5.0 软件对相关病例对照研究进行Meta分析。结果 纳入7项合格研究,共 463例患者,Meta分析结果显示：DCF方案治疗晚期胃癌的有效率明显高于ECF方案[OR=1.72, 95%CI(1.18~2.52), P=0.005],差异具有统计学意义;两方案治疗晚期胃癌的周围神经毒性发生率差异具有统计学意义[OR=39.43, 95%CI(12.33~126.13), P<0.00001]。而在3~4度白细胞减少发生率以及3~4度恶心、呕吐发生率方面差异无统计学意义,大多在预防处理后可耐受。结论 DCF方案治疗晚期胃癌的有效率、周围神经毒性发生率均高于ECF方案,不良反应可耐受。     

Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer

To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m(-2) 2-h intravenous infusion, and 5-FU 2600 mg m(-2) plus FA 300 mg m(-2) 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22-75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8-70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median follow-up time of 24.0 months. Major grades 3-4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.     

Phase II study of gemcitabine and cisplatin in the treatment of patients with advanced pancreatic carcinoma

BACKGROUND: Pancreatic carcinoma is considered among the most chemoresistant of human malignancies. The most commonly used cytotoxic single agents, 5-fluorouracil and 2'-deoxy-2',2'-difluorocytidine (gemcitabine), have objective response rates of less than 10% in large studies. Hypothesizing noncross resistance and a synergistic interaction between gemcitabine and cisplatin, early clinical studies have demonstrated significant activity with this combination in patients with several types of malignant disease. A Phase II study was undertaken to determine the efficacy of gemcitabine in combination with cisplatin in patients with locally advanced and metastatic pancreatic carcinoma based on these considerations. METHODS: The eligibility criteria included histologically confirmed, locally advanced, unresectable or metastatic exocrine carcinoma of the pancreas with no prior gemcitabine therapy; prior adjuvant therapy was allowed provided the last day of therapy was at least 6 months prior to starting treatment; clinically measurable or evaluable disease; a Southwest Oncology Group scale performance status of 0-2; a life expectancy of > 12 weeks; and adequate bone marrow, hepatic, and renal function. A total of 42 patients, 4 patients with locally advanced, unresectable disease and 38 patients with metastatic disease, were treated and received a total of 211 cycles of therapy between May 1997 to March 1999. The median age of patients was 61.5 years. The patients were treated in the outpatient setting with a combination of gemcitabine 1,000 mg/M(2) intravenously over 30 minutes administered on Days 1, 8, and 15 of each cycle and cisplatin 50 mg/M(2) intravenously administered after gemcitabine infusion on Days 1 and 15 with adequate prehydration accompanied by adequate urinary output. Cycles were repeated every 28 days. Response and toxicity were assessed according to World Health Organization and standard criteria. RESULTS: The complete and partial response rate among all 42 registered patients was 11 of 42 patients (26%; 95% confidence interval, 0.14-0.42). Stabilization of disease was seen in 15 patients (38%). Two additional patients with metastatic disease who achieved major responses to chemotherapy were rendered free of disease surgically, achieving a complete response status. The median overall survival was 7.1 months (95% confidence interval [CI], 6.3-9.1 months), with 64% of patients alive at 6 months and 19% of patients alive at 12 months. The median time to disease progression was 5.4 months (range, 0.9-20.8 months). Major toxicities were neutropenia and thrombocytopenia, with one episode of neutropenic fever. CONCLUSIONS: The combination of gemcitabine and cisplatin appeared to have significantly greater activity than single-agent gemcitabine in this Phase II study, with tolerable toxicity. The antitumor activity of this combination needs to be confirmed in multi-institutional or comparative trials.     

Phase II trial of cisplatin, etoposide, and 5-fluorouracil in advanced non-small-cell lung cancer: an Eastern Cooperative Oncology Group Study (PB586)

Advanced non-small-cell lung cancer (NSCLC) remains an incurable disease despite significant progress in chemotherapy. We conducted a phase II clinical trial to investigate the efficacy and toxicity of a cisplatin, etoposide, and 5-fluorouracil (5-FU) combination in advanced metastatic and/or recurrent NSCLC. Forty patients with advanced, recurrent, or metastatic, measurable NSCLC were treated with cisplatin, 60 mg/m2 intravenously (i.v.) on day 1; etoposide, 120 mg/m2/day i.v. on days 1, 2, and 3; and 5-FU. 1,000 mg/m2/day i.v. continuous infusion on days 1 through 5. Treatment was administered in 4-week cycles. Thirty patients had distant metastases and were previously untreated, and 10 patients had recurrent disease after prior treatment with either surgery (1 patient), radiation therapy (5 patients), or both treatments (4 patients). Twenty-nine patients were evaluable for response. Seven (24%) patients achieved a partial remission (PR), 18 (62%) had stable disease (SD), and 8 (14%) had progressive disease (PD). Overall median survival was 7.9 months (range, 0.4-27.4 months). Patients who achieved a PR had a median survival of 23.5 months (9.3-27.4 months). In contrast, patients with SD had a median survival of 9.9 months (2.5-25.3 months), and patients with PD had a median survival of 2.1 months (1-9.3 months). Median duration of response of 27.1 weeks (4.9-76.5 weeks) for patients with PR, and time to progression was 13.4 weeks (3.7-54.5 weeks) for patients with SD. Toxicity was primarily hematologic and gastrointestinal, and there were three deaths due to infection. The combination of cisplatin, 5-FU, and etoposide as administered in this study appears to have considerable toxicity and does not appear to be superior to other cisplatin-containing regimens used for the treatment of advanced NSCLC.