Phase II study of gemcitabine and cisplatin in chemonaive patients with advanced epithelial ovarian cancer

This phase II study evaluated the activity of gemcitabine (Gemzar) plus cisplatin (Platinol) as first-line treatment of advanced epithelial ovarian cancer. Forty-two chemonaive patients with advanced (stage III and IV) epithelial ovarian cancer received gemcitabine 1,250 mg/m(2) on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, up to eight cycles. The median number of cycles completed was 5 (range 2-8). Of the 41 patients evaluable for tumor response, 20 had a partial response and nine had a complete response, for an overall clinical and pathologic response rate of 70.7% (95% CI 56.8-84.6%). Median overall survival for all 42 patients was 23.4 months (95% CI 15.9-29.9 months) and the median progression-free survival time was 10.4 months (95% CI 9.4-13.5 months). The combination was generally manageable. Hematologic toxicity (grade 3/4 neutropenia: 31.0/21.4%; grade 3/4 thrombocytopenia: 9.5/4.8%; grade 3/4 anemia: 11.9/0%) and nausea and vomiting (grade 3/4: 35.7/31.0%) were the most common toxicities. There was one toxic death (septic shock due to hematologic toxicity-induced infection). We conclude that gemcitabine plus cisplatin is active and feasible as first-line treatment of advanced epithelial ovarian cancer. Further clinical trials with the addition of gemcitabine to first-line treatment appear warranted.     

Phase II study of a 4-week capecitabine regimen in advanced or recurrent gastric cancer

Our objective was to evaluate the efficacy and safety of capecitabine in chemotherapy-naive patients with unresectable advanced or metastatic gastric cancer. An open-label multicenter phase II study was conducted for previously untreated patients with advanced or metastatic gastric cancer. Oral capecitabine 828 mg/m2 twice daily was given on days 1-21 every 4 weeks. Baseline characteristics of 60 enrolled patients were: male/female 49/11, median age 64 years (range 28-74), good performance status (ECOG 0-1) in 98% of patients and 27 patients had prior gastrectomy (45%). A median of 4 treatment cycles were administered (range 1-37). Five patients were excluded from the efficacy analysis because they did not meet eligibility criteria. The overall response rate (RR) in the evaluable patient population (n=55) was 26% [95% confidence interval (95% CI) 15-39%] and a further 29% of patients had stable disease. The overall RR in the intent-to-treat population (n=60) was 23% (95% CI 13-36.0%). Median time to progression in the evaluable patient population was 3.4 months (95% CI 1.8-6.1) and overall survival time in the intent-to-treat population was 10.0 months (95% CI 6.4-13.6). The most frequent grade 3/4 drug-related adverse event was hand-foot syndrome (13%), but this was readily managed by treatment interruption and dose reduction. No patients developed grade 3/4 drug-related diarrhea, vomiting, leukopenia or thrombocytopenia. We conclude that this 4-week regimen of capecitabine showed promising activity and was well tolerated as first-line therapy for advanced/metastatic gastric cancer. Further investigation of this regimen is warranted.     

Scheduled administration of low dose irinotecan before gemcitabine in the second line therapy of non-small cell lung cancer: a phase II study

We had previously demonstrated that low dose irinotecan (CPT-11) leads to increased accumulation of cells in S-phase and shows a therapeutic synergy with S-phase specific chemotherapy such as gemcitabine and 5-fluorouracil. In this phase II study, our objectives were to evaluate the tolerability and activity of low dose CPT-11 followed 24 h later by gemcitabine as second line therapy in patients with metastatic non-small cell lung cancer (NSCLC). CPT-11 (60 mg/m) was administered 24 h before gemcitabine (1000 mg/m) on days 1, 2, 8, and 9 every 3 weeks. Twenty-nine patients were evaluable for response. The median follow-up was 7.4 months. Partial response (PR) was seen in two (6.9, 95% confidence interval (CI): 0.009-0.228). PR and stable disease were seen in 22 patients (75.9, 95% CI: 0.564-0.897). The median survival time was 13.8 months (95% CI: 8.1-19.3). The median time to progression was 4.6 months (95% CI: 2.6-6.2). Thirty-eight patients were evaluable for toxicity. Neutropenia (grade 3 or 4) was observed in 27 patients (71%). Eight patients did not receive cycle 2 of therapy owing to prolonged neutropenia. No treatment-related deaths occurred. Scheduled administration of low dose CPT-11, 24 h before gemcitabine in the second line therapy of NSCLC yielded comparable disease control rates (PR and stable disease) when compared with other studies using the two chemotherapy drugs in the traditional sequence. However, this approach was associated with higher grade 3/4 neutropenia and is not recommended for further study in metastatic NSCLC.     

Gemcitabine plus docetaxel as first-line biweekly therapy in locally advanced and/or metastatic urothelial carcinoma: a phase II study

The purpose of the study was to evaluate objective response rate, survival and toxicity of the combination of gemcitabine-docetaxel administered on a biweekly schedule as first-line treatment in advanced/relapsed or metastatic urothelial carcinoma. Treatment consisted of the sequenced administration of gemcitabine 1500 mg/m(2) and docetaxel 60 mg/m(2) (2 h intravenous infusion) on days 1, 14 of a 28-day cycle for 6 months. A total of 33 patients, 22 men and 11 women, were enrolled, aged 41-75 years (median 64 years). The majority of patients had a good performance status (94%; status<2). Thirteen patients had locally advanced disease (39%) and 20 metastasic disease (41%). A total of 178 treatment cycles were administered with a median number of 5.4 cycles for a patients (range 2-8). Toxicity was primarily hematologic with the most frequent grade >2 being neutropenia (11%), with three episodes of febrile neutropenia. Anemia and thrombocytopenia were milder and had a lower incidence. The most frequent nonhematological toxicities were alopecia, followed by asthenia. Cardiac and pulmonary toxicity was minimal. No toxic deaths were recorded during study and follow-up. Overall response rate was 53.1%, including four complete responses (12.5%) and 13 partial responses (40.6%), whereas six patients (18.8%) had disease stabilization. Median time to progression was 10.2 months (95% confidence interval: 5.1-13.7), with a median survival of 14.8 months (95% confidence interval: 9.4-20.2) after an observation of 30 months (range 4-30+). The results of this study suggested that combination therapy with gemcitabine and docetaxel administered twice a week is particularly active and well tolerated as first-line treatment in advanced and/or metastatic urothelial carcinoma. Once data are confirmed in a larger study and longer follow-up, the favorable toxicity profile of this regimen may offer an interesting alternative to the cisplatin-based regimen.     

A randomized phase II study of recombinant human endostatin plus gemcitabine/cisplatin compared with gemcitabine/cisplatin alone as first-line therapy in advanced non-small-cell lung cancer

Purpose Studies indicate that recombinant human endostatin (rh-endostatin) can inhibit tumor endothelial cell proliferation, angiogenesis, and tumor growth. This study assessed the efficacy of the combination of standard gemcitabine plus cisplatin chemotherapy with rh-endostatin in patients with non-small-cell lung cancer (NSCLC). Patients and Methods Chemotherapy-naive patients with stage IIIB to IV NSCLC were randomly (1:1) assigned to receive gemcitabine/cisplatin chemotherapy alone or with 7.5 mg/ m² of intravenously rh-endostatin on days 1 to 14 of each 3-week cycle. The primary end point was objective response rate (ORR). Results Baseline characteristics were similar between treatment arms. The best ORRs for rh-endostatin arm (n = 33) and chemotherapy-alone arm were 37.5% (95% CI: 21.3 to 47.2%) and 28.6% (95% CI: 19.8 to 37.6%), respectively. Median survival was 12.4 months in the rh-endostatin arm and 9.8 months in the chemotherapy-alone arm, and 1-year survival was 51.6% and 38.7%, respectively. Mild palpitions, diarrhea, and liver dysfunction were the most common rh-endostatin-related adverse events. Grade 3/4 hematological toxicities were all reported similar for patients in the two arms. Conclusion The addition of rh-endostatin to gemcitabine plus cisplatin chemotherapy for first-line treatment of NSCLC improves objective response and may improve survival.     

紫杉醇联合顺铂治疗晚期食管鳞癌临床观察

目的 观察紫杉醇联合顺铂治疗晚期食管鳞癌的疗效及不良反应.方法 用紫杉醇注射液175mg/m2静脉滴注3h,第1天;顺铂25mg/m2,静脉滴注,第1-3天.该方案治疗25例晚期食管鳞癌,3周为1个周期.结果 25例患者共完成化疗周期数为104个,其中完全缓解1例(4.1％),部分缓解10例(41.7％),稳定9例(37.5％),进展4例(16.7％),总有效率为45.8％(11/24).至末次随访,死亡20例,全组中位生存期11.0个月(95％CI:8.35～13.65个月),1年生存率37.3％.12例治疗有效病例的中位生存期为12.5个月(95％CI:9.11～ 15.90个月),治疗无效病例的中位生存期为8.0个月(95％CI:5.50～9.50个月),获治疗有效病例的中位生存期显著好于无效病例(P =0.022).主要毒副反应有:白细胞减少(Ⅲ度7例,Ⅳ度1例)、中性粒细胞减少(Ⅲ度5例,Ⅳ度1例)、血小板下降(Ⅲ度1例)和脱发(Ⅱ度19例).结论 紫杉醇联合顺铂方案治疗晚期食管癌有效安全,可作为晚期食管鳞癌首选化疗方案.     

Docetaxel plus fractionated cisplatin is a safe and active schedule as first-line treatment of patients with advanced non-small cell lung cancer: Results of a phase II study

This phase II trial evaluated the efficacy and safety of docetaxel 85 mg/m(2) (day 1) and cisplatin 80 mg/m(2) (administered as 40 mg/m(2) doses each on days 1 and 2) every 3 weeks as first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Forty-two NSCLC patients were enrolled, most of them with stage IV disease (74%). A total of 195 chemotherapy cycles were administered (median 6, range 1-6). All patients were considered evaluable for efficacy and toxicity in an intention-to-treat (ITT) analysis. The overall response rate was 48% (95% CI, 33-64), including one CR (3%) and 19 PRs (45%). Stable disease was found in 6 patients (14%). The median time to disease progression was 4.9 months (95% CI, 4.0-5.7) and the median overall survival was 10.5 months (95% CI, 5.1-16.0). The survival rates at 1 and 2 years were 36.0% (95% CI, 19.9-52.0) and 18.0% (95% CI, 3.9-32.1), respectively. Overall, the combination showed an excellent safety profile. Severe hematological toxicities were uncommon: neutropenia (5% of patients, 1% of cycles) and febrile neutropenia (2% of patients, 0.5% of cycles). Asthenia (12%) was the only grade 3/4 non-hematological toxicity that affected more than 10% of patients. There were no toxic deaths. In conclusion, docetaxel plus fractionated cisplatin as first-line treatment of advanced NSCLC patients showed similar efficacy as the same combination with higher doses of docetaxel but where cisplatin was administered in a single dose. This new schedule shows promise in its excellent hematological and non-hematological toxicity profile. A randomized phase III trial is needed to confirm these results.     

Pooled efficacy analysis from a phase I-II study of biweekly irinotecan in combination with gemcitabine, 5-fluorouracil, leucovorin and cisplatin in patients with metastatic pancreatic cancer

Development of treatments to improve the outcomes achieved with single-agent gemcitabine therapy for metastatic pancreatic cancer remains a research priority. G-FLIP (gemcitabine, 5-fluorouracil, leucovorin and cisplatin) is a four-drug regimen designed to maximize sequence-dependent synergy, while attempting to minimize toxicity among the four drugs. The dose-limiting toxicities and maximum tolerated dose of irinotecan as part of the G-FLIP regimen have been published. For phase II testing, G-FLIP consisted of sequential gemcitabine 500 mg/m2 at a fixed rate of 10 mg/m2/min, irinotecan 120 mg/m2, bolus 5-fluorouracil 400 mg/m2 and leucovorin 300 mg, followed by a 24-h 5-fluorouracil infusion of 1500 mg/m2 on day 1 and cisplatin 35 mg/m2 on day 2. Cycles were repeated every 14 days. Thirty-three patients with metastatic pancreatic cancer (22 men and 11 women) were treated and 31 were evaluable. Median patient age was 63 years (range 44-78 years) and median Karnofsky performance status score was 70-80. Estimated median time to disease progression was 171 days (6.1 months) and Kaplan-Meir-estimated median overall survival was 229 days (8.1 months). Twelve- and 18-month survivals were 33 and 21%, respectively. As per Response Evaluation Criteria in Solid Tumors criteria, 13 patients had stable disease, seven (22%) attained a partial response, and 10 (32%) had disease progression. One patient attained a complete response and two were not evaluable (one withdrew consent and one died suddenly, each after cycle 1). Treatment generally was well tolerated. Grade 3-4 toxicities/patient were thrombocytopenia (3.1%), leukopenia (15%), neutropenia (21%), neutropenic fever (3%), fatigue (18%) and thrombosis (12.5%). Common grade 1-2 toxicities per patient included nausea/vomiting (69%), diarrhea (45%), constipation (21%) and fatigue (39%). In conclusion, G-FLIP is a feasible outpatient regimen with acceptable toxicity for metastatic pancreatic cancer patients. Disease control rate (stable disease rate plus partial or complete responses) and 1-year survival outcomes are encouraging.     

GS方案一线化疗后序贯替吉奥治疗晚期胰腺癌的临床观察

目的 比较晚期胰腺癌一线GS方案化疗后疾病得到控制者序贯替吉奥（S-1）单药治疗的疗效和对生存期的影响。方法 32例患者经一线GS（吉西他滨＋替吉奥）方案化疗4周期后,获得疾病控制的晚期胰腺癌患者,随机（1∶1）分为序贯S-1组（S-1组）和随访观察组（观察组）。每治疗2周期后评价疗效,观察无进展生存时间（PFS）、总生存时间（OS）及不良反应。结果 32例患者均可评价疗效。S-1组共接受93周期单药S-1化疗,S-1组和观察组中位PFS分别为7.0个月和5.2个月,中位OS分别为10.7个月和7.5个月,2组PFS和OS比较差异均有统计学意义（P〈0.05）。S-1组不良反应大多数表现为1～2级,3～4级仅有1例粒细胞减少及1例腹泻,2组之间差异无统计学意义（P〉0.05）。结论 晚期胰腺癌一线GS方案化疗后疾病得到控制者序贯S-1单药治疗安全有效,能显著延长患者的PFS及OS,且不良反应轻。     

Phase II study of docetaxel alternating with cisplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer

The objective of this study was to evaluate a regimen of full doses of docetaxel and cisplatin, using an alternating schedule, as first-line therapy for patients with inoperable non-small cell lung cancer (NSCLC). The standard concomitant schedule does not allow full doses of both drugs to be administered. We wanted to see if there was an advantage to be gained by administering full doses of both docetaxel and cisplatin, using a different schedule. Docetaxel 100 mg/m2 was given once every 6 weeks from week 1 and cisplatin (120 mg/m2 for two doses and 100 mg/m2 thereafter) once every 6 weeks from week 4, for six cycles (three docetaxel and three cisplatin). Thirty-six of the 44 patients enrolled were evaluable for efficacy. Forty-eight percent of the patients had good (KPS 90-100%) performance status. A median of five cycles was administered, for which no dose reductions were necessary. There were 13 of 36 partial responses (36%; 95% CI 21-54%) and 15 of 36 patients achieved stable disease (42%). The median duration of response was 10.5 months, the median time to progression was 4.5 months and the median survival was 9 months. The 1 and 2 year survival rates were 39 and 16%, respectively. The most frequent grade 3-4 toxicities were nausea (23% of patients), vomiting (18%) and neutropenia (77%). Infections were also common, but not severe. The alternating schedule produced response, toxicity and survival figures that compared favorable with those using the concomitant schedule. This study could serve as a model for future studies of non-cisplatin-containing regimens, in which full doses of docetaxel could alternate with full doses of other new agents active against NSCLC.     

Prospective multicenter phase II study of irinotecan as third-line therapy in metastatic colorectal cancer and progression after bolus and infusional 5-fluorouracil

Irinotecan has proven anti-tumor activity as induction treatment in combination with 5-fluorouracil (5-FU) or as second-line treatment after 5-FU in patients with metastatic colorectal cancer. The aim of the present phase II study was to evaluate irinotecan as third-line chemotherapy in patients with colorectal cancer after sequential treatment with bolus 5-FU followed by an infusional 5-FU regimen. Patients pretreated with bolus 5-FU/folinic acid and the infusional 5-FU/folinic acid regimen were treated with 350 mg/m irinotecan i.v. once every 3 weeks in a multicenter phase II study. Tumor size was measured every cycle and treatment with irinotecan was continued until the occurrence of progressive disease or unacceptable toxicity. A total of 50 pretreated patients were included. Of the 45 evaluable patients, 13.3% [n=6, 95% confidence interval (CI) 5.1-26.8] attained a response (complete/partial response) to treatment lasting 5.6 months (95% CI 4.2-6.3) and in four patients response has been confirmed (8.9%, 95% CI 2.5-21.2). Disease stabilization was noted in 51.1% of the patients (n=23, 95% CI 35.8-66.3). The median duration of response/disease stabilization was 4.2 months (95% CI 3.2-6.0). Median overall survival was 7.9 months (95% CI 6.1-11.1), corresponding to a calculated 1-year survival of 28.3% (95% CI 15.2-41.3). Severe neutropenia occurred in 14% (n=7) and anemia grade III in 6% of the patients (n=3). The most frequent non-hematological toxicity grade III/IV related to treatment was diarrhea in 24% of the patients (n=12), followed by vomiting in 8% (n=4) and constipation as well as infection in two patients each (4%) (evaluable n=50). We conclude single-agent irinotecan is an effective and well-tolerable treatment in pretreated patients with metastatic colorectal cancer after failure of bolus and infusional 5-FU/folinic acid regimens. Elderly patients had the same probability to respond.     

Mitomycin C continuous infusion as salvage chemotherapy in pretreated patients with advanced gastric cancer

Our purpose was to evaluate the safety and therapeutic activity of continuously infused mitomycin C in patients with recurring or progressive metastatic gastric cancer following first-line chemotherapy. Patients were treated with mitomycin C 20 mg/m2 i.v. over a time period of 120 h followed by a 3-week rest period. All patients received prednisone 50 mg p.o. prophylactically for 5 days to prevent hemolytic uremic syndrome and pulmonary side effects. Twenty-two consecutively enrolled patients were assessable for toxicity and 20 for response evaluation completing at least one full course of chemotherapy (two patients evaluable but not measurable). Patient characteristics: median age: 63 years (39-76); Sex (M/ F): 13/9; median Karnofsky status: 70% (50-100%); resection of primary tumor n = 12 (55%); sites of metastases: liver n = 17 (77%), locally advanced n = 10 (45%), peritoneum n = 13 (59%), lungs n=5 (23%), bone n=3 (14%) and lymph nodes n=14 (64%). Previous chemotherapy regimens: bolus 5-FU/folinic acid n=6 (27%), ELF n=4 (18%), EAP n=3 (14%) and continuous 5-FU/folinic acid/cisplatin/paclitaxel n=9 (41%). In 20 evaluable patients one complete and five partial remissions were observed; overall response rate 30.0% [95% confidence interval (CI): 9.1-50.9%] with a median response duration of 2.1 months (range: 2-6). The median survival was 3.6 months (95% CI: 2.1-6.0) resulting in a 6-month survival rate of 30% since start of mitomycin C. WHO grade III/IV mucositis, diarrhea and fever/infection occurred in 9% of patients each. Cumulative thrombo- and leukocytopenia (WHO grade II/IV) were observed in four and two patients, respectively. Treatment had to be stopped early in two patients. No severe renal dysfunction, pulmonary toxicity or evidence of hemolytic uremic syndrome was observed. Fatigue during the 120 h infusion of mitomycin C was common (11 of 22 patients). We conclude that continuous infusion of mitomycin C is feasible on an outpatient basis, revealing an acceptable toxicity. Mitomycin C demonstrates single-agent activity in pretreated gastric cancer, but has only limited efficacy following cisplatin/paclitaxel-based first-line chemotherapy.     

Docetaxel and gemcitabine combination therapy in advanced transitional cell carcinoma of the urothelium: results of a phase II and pharmacologic study

Our objective was to determine the response to gemcitabine plus docetaxel in advanced urothelial transitional cell carcinoma in a phase II trial, and gemcitabine distribution between plasma and erythrocytes, following docetaxel administration. Patients with locally advanced or metastatic transitional cell carcinoma, following a maximum of one prior chemotherapy regimen, were given gemcitabine 800 mg/m on days 1 and 8 plus docetaxel 85 mg/m on day 8, every 21 days. Gemcitabine was measured in the plasma and erythrocytes of nine patients before and after docetaxel administration. Thirty-four patients (median 63 years; range 49-79 years), of whom seven had prior chemotherapy and 27 were chemotherapy-naive, received a median of six cycles (range 1-6). Complete and partial remissions were observed in two and 16 (including three pretreated) patients, respectively, for an overall response rate of 53%. Median response duration was 5 months (range 1-39+). Haematoxicity was manageable, despite grade 3 infections in 24% of patients, but other toxicities were mostly mild. An apparent shift of gemcitabine from plasma to erythrocytes occurred after docetaxel in five of six patients evaluable for this analysis. We conclude gemcitabine plus docetaxel is tolerable and highly active in treated and untreated patients with advanced transitional cell carcinoma.     

替吉奥和吉西他滨分别联合顺铂一线治疗EGFR野生型的晚期非小细胞肺癌的临床观察

目的:比较替吉奥联合顺铂方案和吉西他滨联合顺铂方案一线治疗表皮生长因子受体(EGFR)基因野生型的晚期非小细胞肺癌的疗效和安全性。方法:选取2010年7月-2011年12月收治的68例符合入组标准的EGFR基因野生型的晚期非小细胞肺癌患者,将其随机分为2组,观察组采用替吉奥联合顺铂方案进行一线化疗;对照组采用吉西他滨联合顺铂方案进行一线化疗。比较2组患者的近期疗效、无进展生存期和不良反应。结果:替吉奥联合顺铂组(观察组)和吉西他滨联合顺铂组(对照组)的总有效率分别为41.2%和38.2%,差异无统计学意义(P>0.05);中位无进展生存期分别为5.4个月和5.1个月,差异无统计学意义(P=0.088);不良反应中替吉奥组的血小板降低发生率(11.8%)低于吉西他滨组,差异有统计学意义(P<0.05)。结论:替吉奥联合顺铂方案一线治疗EGFR基因野生型的晚期非小细胞肺癌具有较好疗效,且不良反应较轻。     

Single-agent capecitabine maintenance therapy after response to capecitabine-based combination chemotherapy in patients with metastatic breast cancer

We performed an analysis of the efficacy of capecitabine monotherapy as maintenance treatment for metastatic breast cancer (MBC) after response to capecitabine-based chemotherapy [capecitabine plus docetaxel (XT) or vinorelbine (XN)] as a first-line or a second-line treatment. Sixty-four Chinese patients with histologically confirmed MBC received capecitabine maintenance therapy after disease stabilization or maximal response to capecitabine-based combination chemotherapy. Single-agent capecitabine was administered at a dose of 1000 mg/m(2) twice daily for 14 days, followed by a 7-day rest period, every 3 weeks. The median time to progression, the primary endpoint of the study, was 4.4 months (95% confidence interval, 3.4-5.4 months). Fifty-nine patients were evaluable for response. Capecitabine maintenance therapy produced an objective response rate of 5.1% (95% confidence interval, 3.9-6.3%). The incidence of grade 3/4 leukopenia (3.1%) and neutropenia (4.7%) was significantly lower (P<0.001) with capecitabine monotherapy than with combination chemotherapy (46.9 and 54.7%, respectively). Conversely, the incidence of grade 3 hand-foot syndrome was higher with capecitabine maintenance therapy than with combination therapy (14.1 vs. 0%, respectively; P=0.003). Capecitabine monotherapy is an effective maintenance treatment after response to capecitabine-based combination chemotherapy in MBC with a favorable safety profile.     

Salvage chemotherapy with mitomycin C,ifosfamide, and cisplatin (MIC) for previously treated metastatic or recurrent esophageal squamous cell carcinoma

The patients with metastatic or recurrent esophageal cancer are incurable. A number of patients who progress after first-line chemotherapy may still be fit for second-line treatment. However, there is no currently established effective and tolerable salvage chemotherapy. We investigated the activity and tolerability of MIC in patients who had failed to prior chemotherapy for metastatic or recurrent esophageal squamous cell carcinoma. MIC (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) was given in day 1 as an outpatient regimen and repeated every 3 weeks. All 32 enrolled patients were male with median age of 57 years. Prior esophagectomy had been performed in 21 patients (65.6%) and 11 patients (34.4%) were metastatic disease at initial diagnosis. Nineteen patients (59.4%) were treated with MIC as second-line chemotherapy. Prior first-line chemotherapy regimens consisted of 5-FU/cisplatin and capecitabine/cisplatin combinations. Overall response rate was 12.5% with no CR, and disease control rate was 37.5%. Grade 3/4 neutropenia was observed in 21 % of patients and grade 3/4 febrile neutropenia was seen in only one patient. There was no treatment-related mortality. Median PFS was 2.0 months (95%CI = 1.4-2.5) and the median OS was 5.2 months (95%CI = 3.3-7.0) with no significant difference between numbers of prior chemotherapy regimen. MIC chemotherapy has modest activity as a salvage regimen with tolerable toxicity, and could be one of the chemotherapy treatment options for patients with advanced or recurrent esophageal squamous cell carcinoma for whom previous chemotherapy has failed.     

Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine

Gemcitabine is widely used for the treatment of advanced biliary tract cancer (BTC) as first-line chemotherapy. However, there is no standard chemotherapy for patient with advanced BTC refractory to gemcitabine. We conducted a multicenter phase II study of S-1 monotherapy as second-line chemotherapy for patients with advanced BTC that were refractory to gemcitabine. S-1 was administered orally at a dose of 80 mg/m(2) for 28 days, followed by 14 days of rest. This regimen was repeated every 6 weeks. Tumor response was assessed every two cycles using the Response Evaluation Criteria in Solid Tumors version 1.0. Twenty-two patients were enrolled between March 2007 and January 2010, with 14 patients (64%) representing cases of recurrence after surgery. The overall response rate was 22.7%, and the overall disease control rate was 50.0%. The median overall survival time was 13.5 months (95% CI, 7.1-23.1 months) and the median time-to-progression was 5.4 months (95% CI, 2.6-17.2 months). Grade 3/4 toxicities included neutropenia (5%) and anemia (5%). The most common non-hematological toxicities were nausea (27%), anorexia (55%), and pigmentation (32%). In conclusion, S-1 monotherapy is feasible and moderately efficacious second-line chemotherapy for advanced BTC.     

Modified docetaxel,cisplatin and fluorouracil therapy as the first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck cancer: a retrospective study

Aim: Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) therapy has been shown to be a well tolerated and highly effective regimen for metastatic gastric carcinoma. Herein we investigated the effectiveness of the mDCF combination as the first-line treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC).

Methods: A total of 80 patients with recurrent/metastatic HNSCC who were treated with mDCF between 2009 and 2015 were enrolled into this study. All patients were treated in the first-line with 2–6 cycles of mDCF chemotherapy which consisted of docetaxel 60?mg/m² intravenously (IV) on day 1, cisplatin 60?mg/m² IV on day 1, and 5-fluorouracil 600?mg/m² IV for 5 days of continuous infusion, with cycles repeated every 21 days.

Results: The most common grade 3–4 toxicities were neutropenia (22.5%), anemia (10%), thrombocytopenia (7.5%), nephrotoxicity (1.3%), hepatotoxicity (1.3%), and diarrhea (2.5%). Twelve patients (15%) experienced a febrile neutropenic episode. Dose modification was required in 22 (27.5%) of the patients due to drug toxicity. Complete response was achieved in 2.5% of all patients, while partial and stable responses were reported to be 43.8% and 25%, respectively, with a disease control rate of 71.3%. The median progression-free and overall survival was 7 (95% CI: 5.3–8.6) and 11.5 (95% CI: 9.4–13.7) months, respectively.

Conclusions: The efficiency of the mDCF combination for induction chemotherapy has been well established previously. To our knowledge, this is one of the largest studies evaluating the survival and safety significance of mDCF chemotherapy as a first-line treatment in patients with recurrent/metastatic HNSCC.     

Epirubicin/docetaxel regimen in progressive breast cancer-a phase II study

The purpose of this investigation was to evaluate the efficacy and toxicity of 6 months' treatment with the combination of epirubicin and docetaxel in metastatic breast cancer. Thirty-eight women (mean age 51 years, range 35-72) with metastatic breast cancer were treated with a regimen of epirubicin 75 mg/m and docetaxel 75 mg/m every 3 weeks, given 4 times if progression was seen upon evaluation after 4 courses or 8 times in responding/stable patients. The patients received 285 cycles of combination treatment and two treatments with docetaxel or epirubicin alone. When neutropenia with fever was observed, further cycles were given with dose reduction. The median cumulative docetaxel dose was 462 mg/m (range 199-600) and that of epirubicin 476 mg/m (range 199-740). The overall response rate was 54% (95% CI 37-71), with a median duration of response of 14.8 months (95% CI 8.8-27.8). Median time to progression was 12 months, median survival 26 months. Neutropenia below 0.5 x 10 /l occurred following 113 (39%) of the total of 285 cycles given; 21 patients (55%) were hospitalized for febrile neutropenia. We conclude that dose tailoring is required in treatment with an epirubicin and docetaxel regimen to avoid grade 3/4 adverse effects in a significant number of patients treated for metastatic breast cancer.     

A multicenter phase II study of the stop-and-go modified FOLFOX6 with bevacizumab for first-line treatment of patients with metastatic colorectal cancer

Currently, no prospective data exists to support a "stop-and-go" modified FOLFOX6 regimen with bevacizumab in metastatic colorectal cancer (mCRC) patients. This study aimed to evaluate the efficacy and safety of this regimen in first-line mCRC patients. Eligible patients (age ≥20 years) had previously untreated mCRC; Eastern Cooperative Oncology Group performance status of 0-2; and adequate hematologic, hepatic, and renal function. The modified FOLFOX6 regimen and bevacizumab (5 mg/kg) was administered intravenously every 2 weeks. After 8 cycles, patients received maintenance therapy with simplified LV5FU2 and bevacizumab until completion of 8 cycles or disease progression. After maintenance therapy, patients received another 8 cycles of modified FOLFOX6 with bevacizumab until completion of 8 cycles or disease progression. We recruited 50 patients between August 2007 and January 2009. The overall response rate was 48% (80% confidence interval [CI]; 38.2-58) with outcomes as follows: complete response, n?=?1; partial response, n?=?23; stable disease, n?=?21; progression, n?=?1; and not evaluated, n?=?4. Median time to treatment failure was 7.7 months (80% CI: 6.2-8.0), and median progression-free survival was 12.8 months (80% CI: 10.8-14). Grade 3/4 toxicities included neutropenia (40%), nausea (4%), diarrhea (14%), thrombosis (4%), and hypertension (4%) et al. Grade 1, 2, or 3 peripheral neuropathy was reported in 38%, 40%, and 10% of patients, respectively. The stop-and-go modified FOLFOX6 and bevacizumab regimen is effective and well tolerated as first-line chemotherapy for mCRC patients.