Expanded phase II trial of gemcitabine and capecitabine for advanced biliary cancer

BACKGROUND: A phase 2 trial of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer led to an objective response in approximately 30% of patients and a median survival of 14 months. In the current study, the authors report further efficacy data of a larger cohort of such patients treated with the GemCap regimen. METHODS: Patients aged >18 years and who had a diagnosis of locally advanced biliary cancer received first-line treatment with capecitabine at a dose of 650 mg/m(2) twice daily for 14 days and gemcitabine at a dose of 1,000 mg/m(2) on Day 1 and Day 8, every 3 weeks until disease progression. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. RESULTS: Between July 2001 and January 2005, 75 patients were enrolled in the study. At a median follow-up of 9.5 months, the overall response rate was 29% (95% confidence interval [95% CI], 19.4-41%), with a median duration of 9.7 months (range, 3-36 months). Three patients achieved complete responses, with a median duration of 17 months (range, 9-27 months). The median progression-free survival and overall survivals were 6.2 months (95% CI, 4.4-8.3 months) and 12.7 months (95% CI, 9.5-31 months), respectively. CONCLUSIONS: The GemCap regimen is active in patients with biliary cancer. Randomized trials are warranted to define the impact of such a regimen on patient survival and quality of life.     

Capecitabine combined with gemcitabine (CapGem) as first-line treatment in patients with advanced/metastatic biliary tract carcinoma

BACKGROUND: Biliary tract carcinoma is an aggressive cancer, with median survival rarely exceeding 6 months. There is currently no established palliative standard of care. A Phase II trial was conducted to study a combination of oral capecitabine and gemcitabine (CapGem) as first-line therapy in patients with advanced and/or metastatic biliary carcinoma. METHODS: Patients with unresectable or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder carcinoma were enrolled. Eligible patients had histologically or cytologically confirmed, measurable adenocarcinoma and had not received prior therapy with capecitabine or gemcitabine. Treatment consisted of intravenous (i.v.) gemcitabine (1000 mg/m(2) on Days 1 and 8) plus oral capecitabine (650 mg/m(2) twice daily on Days 1-14) every 3 weeks for up to 6 cycles. Tumor response, survival, and safety were determined. RESULTS: A total of 44 patients were evaluable. Primary tumor sites were: intrahepatic (n = 14) and extrahepatic biliary duct (n = 16); gallbladder (n = 7); and ampulla (n = 7). Fourteen (32%) patients had a partial response and 15 (34%) patients had stable disease. Median time to disease progression and overall survival were 6.0 (range, 3.8-8.1) and 14 (range, 11.4-16.6) months, respectively. The 1-year survival rate was 58%. No Grade 4 adverse events were seen. Transient Grade 3 neutropenia/thrombocytopenia and manageable (almost invariably Grade 2) nausea, diarrhea, and hand-foot syndrome were the most common adverse events. CONCLUSIONS: CapGem is an active and well tolerated first-line combination chemotherapy regimen for patients with advanced/metastatic biliary tract carcinoma that offers a convenient home-based therapy.     

Single-agent gemcitabine in the treatment of advanced biliary tract cancers: a phase II study

OBJECTIVE: Patients with advanced biliary tract cancers have a dismal prognosis. The aim of this study was to evaluate the efficacy and safety of gemcitabine as a single agent in the treatment of patients with unresectable biliary tract cancers. METHODS: From May 2002 to April 2004, 23 chemotherapy-na?ve patients with locally advanced or metastatic biliary tract adenocarcinomas were enrolled. The median age was 59 years (range 37-76). Fifteen patients (65.2%) had cholangiocarcinomas and eight (34.8%) had gallbladder adenocarcinomas. Patients received gemcitabine 1000 mg/m(2) over 60 min once a week for 2 weeks followed by a week off therapy. Treatment was discontinued when unacceptable toxicities occurred or there was evidence of disease progression. RESULTS: A total of 110 cycles of chemotherapy were performed with a median of four cycles (range 1-10). The median follow-up was 13.4 months. Among the 23 patients, six (26.1%) had a partial response, eight (34.8%) had stable disease and nine (39.1%) had disease progression despite treatment. The overall response rate was 26.1% [95% confidence interval (CI) 22.08-30.12]. The median time to disease progression was 8.1 months (95% CI 3.33-12.87) and the median overall survival was 13.1 months (95% CI 1.64-24.56). Toxicities were generally mild and treatment was well tolerated. Of the 23 patients, one patient experienced a grade 3-4 neutropenia and one a grade 3-4 thrombocytopenia; however, no cases of febrile neutropenia or treatment-related deaths were noted. CONCLUSION: In this phase II trial, therapy with gemcitabine was well tolerated and clinically active in patients with locally advanced or metastatic biliary tract cancers.     

Phase II trial of gemcitabine combined with cisplatin in patients with inoperable biliary tract carcinomas

Objectives The aim of this phase II study was to evaluate the response rate to gemcitabine combined with cisplatin in patients with locally advanced, metastatic or recurrent biliary tract cancer who had received no prior chemotherapy. Methods The treatment consisted of cisplatin 70 mg/m² in intravenous infusion followed by gemcitabine 1,250 mg/m² in 30-min intravenous infusion on days 1 and 8, repeated every 3 weeks until disease progression, unacceptable toxicity, patient’s refusal or up to 8 cycles. Results Thirty-nine patients with advanced biliary cancer were enrolled between March 2003 and August 2003. Fourteen patients (40%) had gall bladder cancer and 20 patients (57%) had cholangiocarcinoma. Thirty-two patients (91%) had metastatic disease at study entry with liver being the most commonly involved site of metastasis. About 84.5 and 94.2% of the initially planned dose were administered for gemcitabine and cisplatin, respectively. In the ITT population (n = 35), six partial responses were observed for an objective response rate of 17.1% (95% CI; 4.7–29.6%). Ten patients (28.6%) had stable disease, 16 (45.7%) progressed, and three (8.6%) were not evaluable. For the 35 patients in the ITT population, the median overall survival time was 8.6 months (95% CI; 6.1–10.4 months). The median time to disease progression was 3.2 months (95% CI; 2.3–4.9 months) and the median time to treatment failure was 3.1 months (95% CI; 1.9–4.1 months). Among the six tumor responders, the median duration of tumor response was 7.3 months (95% CI; 5.6–11.0 months). The most common grade 3/4 maximum toxicities were nausea (3.4%) and vomiting (2.7%). Conclusion The combination chemotherapy with gemcitabine and cisplatin in this trial demonstrated moderate antitumor activity with favorable toxicity profile. Supported by Korean Cancer Study Group.     

吉西他滨联合卡培他滨治疗41例复发或转移性胆管细胞癌的临床疗效和安全性观察

目的 观察吉西他滨联合卡培他滨治疗复发或转移性胆管细胞癌的临床疗效和安全性.方法 收集2000年3月至2004年12月间在南京军区福州总医院经病理确诊并符合入组条件的41例复发或转移性胆管细胞癌患者,给予吉西他滨联合卡培他滨方案化疗,观察近期疗效、远期疗效和安全性.结果 36例患者可评价疗效,其中完全缓解(CR)0例,部分缓解(PR)11例,病情稳定(SD)11例、病情进展(PD)14例;临床有效率为30.1%,临床受益率为61.1%.患者的中位生存时间和中位疾病进展时间分别为10个月和6个月.化疗后常见的毒副反应为胃肠道反应、乏力和手足综合征等,且以Ⅰ、Ⅱ级毒副反应居多.结论 卡培他滨联合吉西他滨治疗复发或转移性胆管细胞癌是安全和有效的,值得开展多中心临床协作研究来进一步探讨.     

A phase II study of capecitabine plus gemcitabine in patients with locally advanced or metastatic pancreatic cancer

PURPOSE: This open-label, multicenter phase II study was conducted to investigate the efficacy and safety of capecitabine plus gemcitabine combination chemotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: We enrolled 63 patients who received capecitabine 830 mg/m(2) orally twice daily on days 1-21 plus gemcitabine 1000 mg/m(2) as a 30-min infusion on days 1, 8 and 15 every 4 weeks for up to six cycles. RESULTS: A total of 14 patients had partial responses giving an overall response rate of 22% (95% confidence interval [CI] 13-34%) in the intent-to-treat population. The median time to progression and overall survival were 3.9 months (95% CI 3.5-5.7) and 7.5 months (95% CI 5.0-10.0), respectively, and 1-year survival rate was 27.1% in the intent-to-treat population. Capecitabine plus gemcitabine was well tolerated. Grade 3 hematological adverse events were neutropenia (21%) and thrombocytopenia (2%); the only grade 4 hematological events were anemia (2%) and neutropenia (6%). Non-hematological adverse events were mainly gastrointestinal events and hand-foot syndrome, which affected 16% of patients. Grade 3/4 non-hematological events were infrequent. CONCLUSION: The combination of capecitabine plus gemcitabine appears to be active and well tolerated as first-line treatment in patients with advanced/metastatic pancreatic cancer.     

S-1 and Gemcitabine as an Outpatient-based Regimen in Patients with Advanced or Metastatic Pancreatic Cancer

Objective: The standard beneficial chemotherapy proved for patients withpancreatic cancer is a regimen containing gemcitabine. Noveloral fluoropyrimidine, S-1, can be added to gemcitabine to improvethe efficacy of chemotherapy and to provide better conveniencefor patients. We aimed to evaluate the efficacy and safety ofS-1 plus gemcitabine combination chemotherapy as a first-linetreatment in patients with locally advanced or metastatic pancreaticcancer. Methods: Patients with histologically confirmed, bidimensionally measurableadvanced/metastatic pancreatic cancer were eligible for thestudy. Chemotherapy consisted of S-1 (30 mg/m² p.o. bid fromDay 1 to 14) and gemcitabine (1000 mg/m² on Days 8 and 15) every3 weeks based on the results of a previously reported PhaseI trial. Treatment was repeated until disease progression orunacceptable toxicity occurred. Results: From January 2005 to August 2007, 22 patients were enrolled.Median age was 62 years (range, 50–73). Nineteen patients(86.3%) had metastases and of these, 11 patients (57.9%) hadmultiple liver metastases. The overall response rate was 27.3%(95% CI, 8.7–45.9), with a partial response in six patients,stable disease in nine (40.9%) and progressive disease in seven(31.8%). With a median follow-up of 25.4 months, the mediantime to progression and overall survival were 4.6 (95% CI, 2–7.2months) and 8.5 months (95% CI, 6.8–10.1 months), respectively,and 1-year survival rate was 27.3%. S-1 plus gemcitabine waswell tolerated. Grade 3/4 hematological adverse events wereneutropenia (9.1/9.1%) and anemia (4.5/0%). Non-hematologicaladverse events were mainly gastrointestinal events. Twenty patients(91%) received chemotherapy on an outpatient basis. Conclusions: Combination chemotherapy of S-1 plus gemcitabine appears tobe active and well tolerated as first-line treatment in patientswith advanced/metastatic pancreatic cancer.     

Gemcitabine, 5-fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma: a North Central Cancer Treatment Group phase II trial

BACKGROUND: Gemcitabine has broad activity in a variety of solid tumors including biliary tract carcinomas. The authors evaluated 6-month survival, response, and toxicity associated with a combination of gemcitabine, 5-fluorouracil (5-FU), and leucovorin (LV) in patients with unresectable or metastatic biliary tract or gallbladder adenocarcinoma (ACA). METHODS: A 4-week course included 1000 mg/m2 gemcitabine by intravenous infusion over 30 minutes on Days 1, 8, and 15, 25 mg/m2 LV by intravenous push, and 600 mg/m2 5-FU by intravenous push after LV. RESULTS: Forty-two patients were enrolled in 6 months, 35 of whom had metastatic disease. Patients with biliary tract ACA included 24 with hepatic disease (19 patients had intrahepatic disease and 5 patients had extrahepatic disease) and 4 with disease in the ampulla of Vater. All patients were evaluable and received a median of 4 courses of treatment (range, 1-21 courses). Commonly occurring severe toxicity (NCI CTC Grade 3 or worse) included: dyspnea (four patients), nausea (four patients), fatigue (seven patients), thrombocytopenia (six patients), emesis (four patients), and diarrhea (four patients). Five partial responses (9.5%) occurred, 3 of which were sustained for > or = 8 weeks. No treatment-related deaths occurred. Thirty-two patients had disease progression and 38 died after a median follow-up of 20 months (range, 1.4-24 months). The median time to disease progression was 4.6 months (95% confidence interval [95% CI], 2.4-6.6%). The median survival period was 9.7 months (95% CI, 7-12%). CONCLUSIONS: This combination regimen was manageable in patients with advanced biliary tract and gallbladder ACA. Of 42 patients, 24 (57%) survived > or = 6 months, satisfying the primary end point of the trial. The length of survival suggested that gemcitabine, 5-FU, and LV had benefit equivalent to gemcitabine alone.     

伊立替康联合卡培他滨治疗晚期结直肠癌的临床观察

目的：观察伊立替康（CPT-11）联合卡培他滨（Capecitabine，希罗达）治疗晚期结直肠癌的疗效及毒性反应。方法：从2004年2月-2006年5月对晚期结直肠癌采用CPT-11联合卡培他滨方案化疗。入组患者均经病理组织学证实，且有可测量病灶。具体方案为：CPT-11250mg／m^2 iv，d1；希罗达1250mg／m^2 po，bid，d1-d14。21天为1个周期，化疗2个周期后评价疗效及毒性反应。结果：可评价疗效者60例，其中完全缓解（CR）4例，部分缓解（PR）22例，有效率（RR）为43．3％，稳定（SD）28例（46．7％），进展（PD）6例（10．0％）。临床受益率为83．3％，疼痛缓解率83．3％。肿瘤中位进展时间7．2个月，中位生存期13．8个月。主要毒副反应为迟发性腹泻和中性粒细胞减少，未出现治疗相关性死亡。结论：CPT-11联合卡培他滨方案治疗晚期结直肠癌患者有较好疗效，毒副反应可以接受。     

吉西他滨联合卡培他滨治疗难治性乳腺癌的临床观察

目的观察吉西他滨联合卡培他滨（GX方案）治疗术后复发的乳腺癌患者的疗效和不良反应。方法50例患者分别接受GX方案化疗3～6个周期,按世界卫生组织（WHO）标准评价疗效及不良反应。结果50例患者均可评价,其中完全缓解（CR）4例（8．0％）,部分缓解（PR）22例（44．0％）,稳定（SD）18例（36．0％）,进展（PD）6例（12．0％）。中位肿瘤进展时间（mTTP）为8．3个月（95％CI：6．55—10．89）,中位总生存时间（mOS）为18．0个月（95％CI：14．34～21．98）。主要不良反应为骨髓抑制和皮疹。结论GX方案治疗晚期乳腺癌安全有效,不良反应较轻,值得临床推广应用。     

Phase II clinical trial of capecitabine and gemcitabine chemotherapy in patients with metastatic renal carcinoma

We report a single institution phase II study of gemcitabine 1200 mg m(-2) i.v. on days 1 and 8 and capecitabine 1300 mg m(-2) twice daily on days 1-14 of each 3-week cycle in patients with metastatic renal carcinoma. Patients had a WHO performance status of 0, 1 or 2. Of the 21 enrolled patients, 19 had received prior immunotherapy or chemoimmunotherapy. All had progressive disease at study entry. In all,19 patients had multiple sites of disease. The median duration of metastatic disease was 12.3 months (range 1.2-78.1 months). Three of the 19 evaluable patients achieved a partial response to treatment, with no complete responses, producing an objective overall response rate of 15.8% (95% CI, 3.4-39.6%). The median time to disease progression was 7.6 months, and median overall survival was 14.2 months. Treatment was reasonably well-tolerated, neutropenia being the most frequently observed grade 3 or 4 toxicity, occurring in 57% of patients. Other side effects were consistent with the established toxicity profile of the two drugs, including diarrhoea, palmar-plantar erythema, fatigue, nausea, vomiting and infection. This combination of gemcitabine and capecitabine has modest activity in immunotherapy-refractory metastatic renal carcinoma with manageable toxicity.     

The combination of a chemotherapy doublet (gemcitabine and capecitabine) with a biological doublet (bevacizumab and erlotinib) in patients with advanced pancreatic adenocarcinoma. The results of a phase I/II study

BackgroundPreclinical data support the combined inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways in the treatment of pancreatic cancer. Following a dose finding phase I study the efficacy and toxicity of a four-drug regimen utilising the cytotoxic doublet of gemcitabine and capecitabine (GemCap), with the biological doublet of erlotinib and bevacizumab were further assessed in patients with advanced pancreatic cancer.Patients and methodsIn a phase II expansion cohort, patients with chemonaive locally advanced or metastatic pancreatic cancer received gemcitabine (1000 mg/m² D1, 8, 15), capecitabine (1400 mg/m² D1–21), erlotinib (100 mg daily) and bevacizumab (5 mg/kg D1, 15) every 28 days. The primary endpoint was radiological response rate by response evaluation criteria in solid tumours (RECIST). Computed tomography (CT) assessment was performed every 8 weeks. Consolidation radiotherapy was considered in locally advanced patients following six cycles of treatment.ResultsIn total 44 patients (phases I & II) were recruited. The median cycles delivered were 6 (range 1–16). Confirmed radiological responses were seen in 23% (95% confidence interval (CI): 11–38%) of patients. The median progression-free and overall survival for the entire cohort was 8.4 and 12.6 months, respectively. In patients with metastatic disease the median overall survival was 10.1 months. Common grade 3/4 toxicities were; neutropenia 52%, lethargy 32%, diarrhoea 18% and hand-foot syndrome 18%.ConclusionThe combination of gemcitabine, capecitabine, erlotinib and bevacizumab was feasible with a manageable toxicity profile and demonstrated encouraging efficacy data in a good performance status population.     

Evaluation of two modified ECF regimens in the treatment of advanced gallbladder cancer

Gallbladder cancer is a rare disease and it is associated with a poor clinical outcome and survival. A standard therapy for it has not been established yet. The aim of this study is to evaluate efficacy and safety of two modified ECF regimens in advanced gallbladder cancer patients. Clinical data of 38 patients with advanced gallbladder cancer treated with modified ECF regimen were reviewed retrospectively. Of them, 21 patients received an epirubicin, cisplatin, and 5-FU/LV combination therapy. Seventeen patients received a chemotherapy of epirubicin, cisplatin, and capecitabine. Partial response was achieved in fourteen (36.84%) patients with a median duration of 5 months (range, 3-13 months), while stable disease was achieved in eight patients (21.05%). The median time to progression was 4.0 months (95% CI, 3.62-4.58 months). And the median overall survival was 9.8 months (95% CI, 7.26-12.34 months). Responders demonstrated better survival than non-responders (median survival time: 16 vs. 6.9 months, P = 0.008). The median survival time for epirubicin-, cisplatin- and capecitabine-treated patients was 9.2 versus 8.9 months for epirubicin-, cisplatin- and 5-FU/LV-treated patients. There was no statistical difference between both treatment groups in terms of survival time (P = 0.769). Regimen-related toxicity resulted in at least one treatment delay or dosage reduction in 63.2 and 34.2% patients, respectively. There were no chemotherapy-related deaths during the study. Modified ECF regimen with epirubicin, cisplatin and 5-FU/LV or substituting capecitabine for 5-FU/LV is still a potentially effective therapeutic chemotherapy for patients with advanced gallbladder cancer, and toxicity was manageable. There was no remarkable difference in efficacy between the two regimens.     

Capecitabine and radiation therapy preceded and followed by combination chemotherapy in advanced pancreatic cancer

PURPOSE: The primary objective of this study was to evaluate the tolerance and toxicity of radiation therapy (RT) and capecitabine in patients with advanced, unresectable pancreatic carcinoma. To control micrometastatic disease, combination chemotherapy (gemcitabine and cisplatin) before and after combined modality therapy (CMT) was planned. METHODS AND MATERIALS: Patients with unresectable or metastatic pancreatic cancer were eligible. Gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 were administered on Days 1 and 8 of a 21-day cycle for two cycles. RT was then given to a dose of 50.4 Gy in 1.8 Gy fractions. Patients were treated with capecitabine 1330 mg/m2 daily during RT. After CMT, two additional cycles of gemcitabine and cisplatin completed the treatment. RESULTS: Twenty-three patients were treated. Eighteen patients completed CMT. One patient was removed from study during CMT for toxicity issues. Treatment delays and dose reductions were common during the final two cycles of gemcitabine and cisplatin as a result of myelosuppression. Median survival was 10.1 months (95% confidence interval [CI] = 7.6, 13.7) for all 23 patients and 12.8 months (95% CI = 8.2, 18.9) for 18 patients without metastasis. CONCLUSION: Combined modality therapy with RT and capecitabine was well tolerated. Chemotherapy after CMT was difficult to complete owing to cumulative myelosuppression. Survival, response, and toxicity were comparable to infusional 5-fluorouracil and RT.     

白蛋白紫杉醇二线治疗晚期胰腺癌的临床观察

目的:探讨白蛋白紫杉醇二线治疗一线含吉西他滨方案化疗失败的晚期胰腺癌患者的疗效和安全性。方法:6例一线含吉西他滨方案化疗失败的晚期胰腺癌患者,给予白蛋白紫杉醇100mg/m2 静脉滴注,d1、d8、d15,28天为1周期。治疗至疾病进展或出现不可耐受的不良反应。根据实体瘤疗效反应评价标准(RECIST)评价疗效,常规毒性判定标准(NCI-CTC 3.0)评价不良反应。结果:6例患者中位治疗时间为2周期（1~8周期）,无CR病例,PR 1例,SD 3例,PD 2例。总有效率为16.7%,疾病控制率为66.7%,中位无疾病进展时间（PFS）为5.3个月,中位总生存时间（OS）为7个月,有2例患者仍存活,随访至今,生存时间分别为54个月和58个月。不良反应主要为骨髓抑制和神经毒性,多为Ⅰ-Ⅱ级,其中1例患者出现Ⅲ级白细胞下降,4例Ⅱ级下降;2例出现Ⅱ级肌肉酸痛,无Ⅳ级不良反应。结论:对于一线含吉西他滨方案化疗失败的晚期胰腺癌患者,白蛋白紫杉醇单药方案化疗可取得一定疗效,患者耐受性好,值得扩大样本量进一步研究。     

Gemcitabine and vinorelbine as first-line chemotherapy for advanced non-small cell lung cancer: a phase II trial

The purpose of this phase II study was to investigate the efficacy and safety of gemcitabine plus vinorelbine as first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Eligibility criteria included cytologically or histologically confirmed NSCLC (stage IIIB or IV), no previous chemotherapy, and bidimensionally measurable disease. Patients received 1000 mg/m(2) gemcitabine and 30 mg/m(2) vinorelbine on days 1, 8 and 15 every 4 weeks up to eight courses. From December 1997 to November 1998, 70 patients (59 stage IV and 11 stage IIIB disease), with a median age of 59 years (range 38-74 years) were enrolled. The intent-to-treat response rate was 41% (95% confidence interval (CI) 30-54%) with 1 complete responder (CR) and 28 partial responders (PRs), 15 patients had stable disease (SD) and 26 progressed (PD). Median survival was 8.3 months (95% CI 6.0-9.9 months), median progression-free survival (PFS) was 4.8 months (95% CI 3.9-5.5 months), and 1-year survival rate was 33.5% (95% CI 24.0-46.8%). Patients received a total of 229 cycles. Haematological and non-haematological toxicities were moderate. Transient World Health Organization (WHO)-grade IV leucopenia and thrombocytopenia occurred in 13 (6%) and two (1%) cycles, respectively. The predominant non-haematological toxicity was local reactions of the veins in 19 (27%) patients (WHO-grade II and III). Neurotoxicity was infrequent, non-cumulative, and reversible. The combination of gemcitabine and vinorelbine has demonstrated activity in metastatic NSCLC, with response and survival rates similar to those of cisplatin-based regimens and a more favourable toxicity profile that is well tolerated in an outpatient setting.     

Gemcitabine, vinorelbine and cisplatin combination chemotherapy in advanced non-small cell lung cancer: a phase II trial

The purpose of this phase II trial was to investigate the efficacy and safety of a combination chemotherapy with gemcitabine, vinorelbine and cisplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Patients with NSCLC stage IIIB or IV disease received 1000 mg/m(2) gemcitabine and 25 mg/m(2) vinorelbine on days 1 and 8 and 75 mg/m(2) cisplatin on day 2, every 3 weeks. From December 1998 to May 1999, 31 patients (21 stage IV and 10 stage IIIB disease), with a median age of 59 years (range 40-72 years) were enrolled. The overall intent-to-treat response rate was 45% (95% confidence interval (CI): 27-64%) with 2 complete responders (CR) and 12 partial responders (PR), 7 patients had stable disease and 10 progressed. Median survival was 12.8 months (95% CI: 6.5-12.8+ months), median time to progression was 5.1 months (95% CI: 3.5-7.7 months), and the 1-year survival rate was 52.9% (95% CI: 36.7-76.2%). Patients with stage IIIB disease had a significantly longer overall survival than patients with stage IV disease (P=0.05). Transient World Health Organization (WHO) grade IV leucopenia, anaemia and thrombocytopenia occurred in 3 (10%), 2 (6%) and 3 (10%) patients, respectively. The predominant non-haematological toxicities were alopecia and nausea/vomiting. 15 patients (48%) had WHO grade II and III alopecia and 14 patients (45%) nausea/vomiting. The combination of gemcitabine, vinorelbine and cisplatin has demonstrated major antitumour efficacy in advanced NSCLC with a manageable toxicity profile.     

Gemcitabine and Cisplatin is a highly effective combination chemotherapy in patients with advanced cancer of the gallbladder

We evaluated the efficacy and toxicity of gemcitabine with or without cisplatin in 11 chemonaive patients with histologically confirmed advanced gallbladder cancer. All were symptomatic and had stage IV disease. Eight patients received gemcitabine 1 g/m2 on days 1 and 8 along with cisplatin 70 mg/m2 on day 1. Three received gemcitabine alone. Treatment cycles were repeated every 21 days. One patient (9%) had complete remission of disease and 6 (55%) achieved a partial response to chemotherapy with an overall response rate of 64%. Median time to progression was 28 weeks and median overall survival was 42 weeks. Toxicity was easily manageable, and no treatment-related deaths occurred. We conclude that gemcitabine in combination with cisplatin may be one of the most effective therapies for patients with advanced gallbladder cancer. If confirmed by others, it may provide an important therapeutic option in managing these patients who otherwise have a dismal prognosis.     

Phase II study of single-agent gemcitabine in patients with advanced biliary tract cancer

Purpose: This phase II study was conducted to evaluate the efficacy and toxicity of single-agent gemcitabine in patients with advanced or metastatic biliary tract cancer. Patients and methods: Gemcitabine 1,000 mg/m² was administered as an intravenous 30-min infusion on days 1, 8, and 15 for every 28 days. Results: Forty chemonaive patients with a median age of 61 (range 33–73) were enrolled, and all 40 patients were involved in efficacy and safety analyses. Seven (17.5%) achieved partial response; 15 (37.5%) had stable disease; 17 (42.5%) had progressive disease; and 1 (2.5%) was not evaluated. The median survival time was 7.6 months, and the 1-year survival rate was 25.0%. Grade 3/4 neutropenia occurred in 12 patients (30.0%), leukopenia in five patients (12.5%), and anemia in four patients (10.0%). The most common grade 3/4 nonhematologic toxicities were elevated ALT (15.0%) and elevated γ-GTP (12.5%). One patient had grade 4 hemolytic uremic syndrome and recovered after discontinuation of gemcitabine. Conclusions: In single-agent therapy, gemcitabine demonstrated moderate efficacy with manageable toxicity in patients with advanced or metastatic biliary tract cancer. Further evaluations are warranted, including the exact impact of gemcitabine on the management of advanced or metastatic biliary tract cancer.     

晚期十二指肠癌患者一线化疗的临床疗效及预后因素分析

目的 探讨晚期十二指肠癌患者一线化疗方案的疗效与安全性以及影响预后的因素。方法 回顾分析本院2008年6月至2016年1月收治的晚期十二指肠癌患者40例,9例未接受化疗,31例接受化疗,其中GEMOX方案13例、FOLFOX方案13例、卡培他滨单药2例和吉西他滨单药3例。采用RECIST 1.1版与NCI CTC 4.0版标准评价化疗的近期疗效和不良反应。生存分析采用Kaplan Meier法并行Log rank检验,多因素分析采用Cox比例风险回归模型。结果 31例化疗患者均可评价疗效和不良反应,共完成化疗146个周期,中位化疗4个周期（2～12个周期）。GEMOX方案组获PR 1例、SD 10例、PD 2例,疾病控制率（DCR）为84.6％;FOLFOX方案组获SD 6例、PD 7例,DCR为46.2％;单药组：卡培他滨获SD 2例,吉西他滨获SD 1例、PD 2例,DCR为60.0％。31例化疗患者的中位生存期（OS）为15.7个月,9例未化疗患者的中位OS为4.4个月,差异有统计学意义（P＜0.001）。GEMOX方案组的中位OS为279个月,FOLFOX方案组为152个月,单药组为152个月,差异无统计学意义（P=0.656）。GEMOX方案组的中位无进展生存期（PFS）为7.8个月,FOLFOX方案组为4.0个月,单药组为5.1个月,差异无统计学意义（P=0.053）。常见不良反应多为1～2级,主要为白细胞减少、中性粒细胞减少、贫血、乏力及恶心等。单因素分析显示,浸润深度、分化程度、是否肝转移及是否化疗与晚期十二指肠癌的预后有关（P＜0.05）。Cox多因素分析显示,分化程度、是否肝转移及是否化疗是影响晚期十二指肠癌患者预后的独立因素。结论 GEMOX方案、FOLFOX方案、卡培他滨单药及吉西他滨单药一线化疗均对晚期十二指肠癌有效,且耐受性良好;其中GEMOX方案可能有更好的生存获益。分化程度、是否肝转移及是否化疗可能是影响晚期十二指肠癌患者的预后因素,临床上可作参考。