吉西他滨联合替吉奥胶囊治疗晚期胰腺癌的疗效观察

目的探讨吉西他滨联合替吉奥胶囊化疗方案与吉西他滨单药治疗进展期胰腺癌的疗效。方法对2008年1月至2011年1月收治的52例晚期胰腺癌患者的临床资料进行回顾性分析,其中28例采用吉西他滨联合替吉奥胶囊方案治疗(A组);24例采用吉西他滨单药治疗(B组)。采用Kaplan-Meier法分析患者的生存时间,并比较两组患者的客观缓解率、临床受益反应(CBR)、中位疾病进展时间、中位生存时间和不良反应。结果 A组有效率明显高于B组(32.1%vs.20.8%),差异有统计学意义(P=0.039)。A组疾病控制率(DCR)高于B组(67.9%vs.45.8%),但差异无统计学意义(P=0.230)。A组患者CBR缓解率高于B组(72.1%vs.46.9%),差异无统计学意义(P=0.41)。A组的中位生存时间为10.2个月(95%CI:8.0～11.8个月),高于B组的8.03个月(95%CI:3.8～10.9个月),差异有统计学意义(P=0.045);A、B两组的中位疾病进展时间分别为3.6个月和3.0个月(P=0.721)。A组的6个月生存率(72.7%)略高于B组(66.8%),但差异无统计学意义(P>0.05)。两组不良反应的发生率也相似(P>0.05)。结论吉西他滨联合替吉奥胶囊治疗方案与单药治疗晚期胰腺癌相比,在客观疗效、中位生存时间表现出一定优势,疾病控制率及临床受益反应也有所提高,且不良反应可耐受,是晚期胰腺癌的有效治疗方案。     

Combination of low-dose cisplatin and gemcitabine for treatment of elderly patients with advanced non-small-cell lung cancer

PURPOSE: To evaluate the feasibility, toxicity and efficacy of the combination of low-dose cisplatin (CDDP) and gemcitabine (GEM) in elderly patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This phase II trial included 46 patients aged 70 years or older with previously untreated advanced NSCLC. All patients were evaluable for response and toxicity. Treatment consisted of CDDP 50 mg/m(2) on day 1 plus GEM 1000 mg/m(2) on days 1 and 8. The regimen was repeated every 21 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: A total of 190 GEM-CDDP courses were administered (median 4.1 courses per patient). The chemotherapy regimen was well tolerated. No patients developed grade 4 toxicity. Grade 3 toxicities were as follows: neutropenia in six patients (13%), and anemia, thrombopenia and nausea/vomiting in one (2%) each. Two patients (4%) had mild nephrotoxicity. Of the 46 patients, 16 had a partial response (35%, 95% confidence interval, CI, 28-52%), 17 (37%) remained stable and 13 (28%) had disease progression. Eastern Cooperative Oncology Group performance status improved in 17 patients (37%), whereas 25 (54%, 95% CI 44-74%) showed a clinical benefit. Median time to progression was 20 weeks. Overall median survival was 44 weeks, with a 1-year actuarial survival rate of 35%. CONCLUSIONS: The combination of low-dose CDDP and GEM for elderly patients with advanced NSCLC is an effective and well-tolerated chemotherapeutic approach.     

Refractory non-small-cell lung cancer responding to combination chemotherapy with docetaxel, gemcitabine and cisplatin

The combination of docetaxel (TXT), gemcitabine (GEM), and cisplatin (CDDP) produced a regression in a squamous cell carcinoma of the lung that had recurred after radiation therapy plus chemotherapy, and was resistant to the combination of carboplatin (CBDCA) with etoposide (ETP) or paclitaxel (TXL). The patient was a 62-year-old man with squamous cell lung cancer, which was first successfully treated by a combination of radiation therapy and chemotherapy, but showed local recurrence after 8 months. Although the recurrence was treated with CBDCA plus ETP and then TXL, the tumor continued to grow with symptomatic progression of airway stenosis. The tumor began to regress after the regimen of TXT, GEM and CDDP was started. This therapy achieved PR with symptomatic improvement. The combination of TXT, GEM and CDDP may be effective for recurrent non-small-cell lung carcinoma, even in patients that have failed to respond to more than one chemotherapy regimen.     

吉西他滨为基础的化疗方案治疗进展期胰腺癌的临床研究

背景与目的:进展期胰腺癌预后差.吉西他滨可以改善胰腺癌患者的生存质量,但吉西他滨联合方案疗效是否优于单药,还存在争议,国内更缺乏相关的临床研究.本研究目的是比较吉西他滨为基础的联合化疗方案与吉西他滨单药治疗进展期胰腺癌的疗效.方法:回顾性分析2000～2005年收治的40例经临床或病理确诊的进展期胰腺癌临床资料,其中吉西他滨单药组15例,吉西他滨剂量为1 000 mg/m2,每周1次,连用7周,休息2周,之后每周1次,连用3周,4周重复;吉西他滨联合治疗组25例,联合化疗方案包括吉西他滨1 000 mg/m2,每周1次,连用2周,分别联合:(1)氟尿嘧啶425～600 mg/m2,静脉滴注或持续静脉泵入,d1-5,3周重复;(2)顺铂60～75 mg/m2,分第1、2天,3周重复;(3)奥沙利铂85～130 mg/m2,d1,3周重复;(4)卡培他滨l000 mg/m2,2次/天,d1-14,3周重复.采用Kaplan-Meier生存曲线分析患者的生存期,并比较两组间的临床受益反应、中位疾病进展时间、中位生存时间和不良反应.结果:吉西他滨联合组与单药组患者的临床受益反应均得到改善(56.0% vs.46.7%),但疾病控制率、中位生存时间、临床受益反应在两组之间差异无统计学意义(P＞0.05),不良反应的发生率也相似(P＞0.05).对Ⅲ～Ⅳ期患者进行分层分析,发现吉西他滨联合组疾病控制率高于单药组(75.0% vs.45.5%),但无统计学意义(P=0.13).结论:吉西他滨联合方案与单药治疗进展期胰腺癌相比,疗效、临床受益反应、中位生存时间两组相似.     

Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell'Italia Meridionale

BACKGROUND: A prospective, randomized Phase III trial was performed to determine whether, compared with gemcitabine (GEM) alone, the addition of cisplatin (CDDP) to GEM was able to improve the time to disease progression and the clinical benefit rate in patients with advanced pancreatic adenocarcinoma. The objective response rate, overall survival rate, and toxicity patterns of patients in the two treatment arms were evaluated as secondary end points. METHODS: Patients with measurable, locally advanced and/or metastatic pancreatic adenocarcinoma were randomized to receive GEM (Arm A) or a combination of GEM and CDDP (Arm B). In Arm A, a dose of 1000 mg/m(2) GEM per week was administered for 7 consecutive weeks, and, after a 2-week rest, treatment was resumed on Days 1, 8, and 15 of a 28-day cycle for 2 cycles. In Arm B, CDDP was given at a dose of 25 mg/m(2) per week 1 hour before GEM at the same dose that was used in Arm A. On Day 22, only GEM was administered. Patients were restaged after the first 7 weeks of therapy and then again after the other 2 cycles. RESULTS: A total of 107 patients entered the trial: Fifty-four patients were randomized to Arm A, and 53 patients were randomized to Arm B. The median time to disease progression was 8 weeks in Arm A and 20 weeks in Arm B; this difference was statistically significant (P = 0.048). In Arm A, one complete response and four partial responses were recorded on the basis of an intent-to-treat analysis, with an overall response rate of 9.2% (95% confidence interval [95%CI], 3-20%). In Arm B, there were no complete responses, whereas 14 partial responses were achieved, with an overall response rate of 26.4% (95%CI, 15-40%). This difference in the overall response rates was statistically significant (P = 0.02). The tumor growth control rate (i.e., total number of patients who achieved complete responses, partial responses, and stable disease) was 42.6% (95%CI, 29-57%) in Arm A and 56.6% (95%CI, 42-70%) in Arm B. A clinical benefit was observed in 21 of 43 patients (49%) in Arm A and in 20 of 38 patients (52.6%) in Arm B without any significant difference. The median overall survival was 20 weeks for patients in Arm A and 30 weeks for patients in Arm B (P = 0.43). Toxicity was mild in both treatment arms, with no significant differences between the two groups except for the statistically higher incidence of Grade 1-2 asthenia in Arm B (P = 0.046). CONCLUSIONS: The addition of CDDP to GEM significantly improved the median time to disease progression and the overall response rate compared with GEM alone. The clinical benefit rate was similar in both arms, whereas the median overall survival rate was more favorable for Arm B, although the difference did not attain statistical significance. The authors conclude that the combination of CDDP and GEM currently may be considered as an optimal treatment for patients with locally advanced and/or metastatic adenocarcinoma of the pancreas.     

低分子肝素联合化疗治疗非小细胞肺癌的随机研究

目的:观察低分子肝素联合MVP方案治疗晚期非小细胞肺癌的短期疗效,毒副反应及对生存期的影响。方法:46例非小细胞肺癌随机分为两组,A组(治疗组)为MVP+肝素;B组(对照组)为单纯MVP。两组均接受MVP方案两周期。化疗方案:MMC 6 mg/m2,VDS 3 mg/m2×2,DDP 90 mg/m2。治疗组加用低分子肝素5 000u皮下注射,化疗前三天起,每日二次,共7天。结果:治疗组有效率56.5％(13/23),中位生存期12.1月(95％CI:8.52～14.64月),一年生存率52.2％。对照组有效率39.1％(9/23),中位生存期8.4月(95％CI:6.15-10.85月),一年生存率34.8％。治疗组中位生存期及一年生存率明显大于对照组(P<0.05)。主要毒副反应为Ⅱ-Ⅲ度血液毒性,消化道反应均为Ⅰ-Ⅱ度。两组间毒副反应比较无显著差异(P>0.05)。结论:低分子肝素联合MVP方案能提高NSCLC的化疗疗效,延长生存,不增加毒副反应。     

A randomized study of cisplatin versus cisplatin plus vindesine for non-small cell lung carcinoma.

Between August 1983 and March 1985, a randomized study was conducted that compared cisplatin (CDDP) (80 mg/m2 on day 1) alone with CDDP plus vindesine (VDS) (3 mg/m2 on days 1, 8, and 15) in 160 consecutive patients with inoperable non-small cell lung cancer (NSCLC). There were no complete responses. The response rate for CDDP plus VDS (22 of 77 patients, 29%) was significantly higher than that for CDDP alone (9 of 78 patients, 12%) (P less than 0.05). However, no difference existed in the median duration of response (20 weeks for CDDP plus VDS versus 20 weeks for CDDP alone) or the median survival time (45 weeks for CDDP plus VDS versus 39 weeks for CDDP alone). No significant differences in toxicity were detected between the two arms; myelosuppression, alopecia, and peripheral neuropathy occurred more frequently with CDDP plus VDS and there was one lethal episode of hepatorenal syndrome in the CDDP plus VDS arm. Among the variables Eastern Cooperative Oncology Group (ECOG) performance status (PS), age, sex, stage, weight loss, serum lactate dehydrogenase (LDH) level, albumin level, histologic cell type, and chemotherapy arm, only chemotherapy arm was a significant factor leading to a major response (P = 0.019, multiple logistic regression analysis). The significant predictors of survival were PS (P = 0.000), sex (P = 0.000), and stage (P = 0.002) (Cox's proportional hazards model), with a PS of 0 or 1, female sex, and lower stage yielding the best survival. Although a significantly higher response rate was obtained in the combination arm than in the single agent arm, the survival benefit to patients receiving such combination chemotherapy was not determined and more effective chemotherapy regimens are required.     

Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

BACKGROUND: This phase II study was initiated to determine the activity and toxicity of a combination of gemcitabine (GEM) and cisplatin (CDDP) in patients with pancreatic cancer. PATIENTS AND METHODS: CDDP 35 mg/m(2) was given as a 30-min infusion and GEM 1000 mg/m(2) as a 30-min infusion. Both drugs were administered once weekly for 2 consecutive weeks out of every 3 weeks to chemonaive patients with locally advanced or metastatic pancreatic cancer. RESULTS: Forty-five advanced pancreatic cancer patients received this regimen for a total of 180 cycles of chemotherapy. One complete and four partial responses have been observed for an overall response rate of 9% (95% confidence interval 10% to 11%). Twenty-one patients (46%) had stable disease and 19 progressed on therapy. The median time to progression was 3.6 months, with a median survival of 5.6 months. A clinical benefit was obtained in nine of 37 patients (24%). Side-effects were mainly represented by hematological toxicity. Grade 3/4 WHO toxicities included neutropenia (6% of the patients) and thrombocytopenia (11%). The dose of GEM and CDDP was reduced in 14 patients (31%) and treatment was delayed in 10 patients (22%). CONCLUSIONS: Our results in terms of response rate, clinical benefit and survival do not support an advantage for the combination of GEM and CDDP given by this schedule.     

The chemotherapy of peritoneal malignant mesothelioma

Peritoneal malignant mesothelioma is a rare disorder with a poor prognosis, and a standard treatment for it has not yet been established. Therefore, treatment of this disorder tends to be selected according to pleura malignant mesothelioma. We analyzed case reports in Japan. The median survival time(MST)with this disease was 12 months and the 1-year survival rate was 47. 3% in the chemotherapy group. It was found through a case-series study that platinum pharmaceutical plus antimetabolite are effective against peritoneal malignant mesothelioma. A gemcitabine(GEM)plus cisplatin(CDDP)regimen had been selected as a conventional treatment, but subsequently, pemetrexed(MTA)was covered by health insurance for pleural malignant mesothelioma in 2007, and the MTA plus CDDP regimen became the standard treatment. However, a phase III trial of GEM plus CDDP regimen and MTA plus CDDP regimen was not performed. There is a need to perform these phase III trials in the future. In our institution, the MTA plus CDDP regimen was the first-line treatment, and the GEM plus CDDP regimen was the second-line treatment against peritoneal malignant mesothelioma. Palonosetron hydrochloride and aprepitant should be used actively in treatment. Also, carboplatin(CBDCA)is effective as an alternative therapy of the CDDP against renal disorder case, but hematotoxicity requires attention.     

GP方案与吉西他滨单药治疗老年人晚期非小细胞肺癌的疗效比较

 目的　比较GP方案与吉西他滨（GEM）单药治疗老年人晚期非小细胞肺癌（NSCLC）的近期疗效、生存状况及不良反应。方法　85例老年Ⅲ～Ⅳ期NSCLC患者按照起始治疗方案的不同分为GP组（43例）及GEM组（42例）。GP组接受GEM 1.0 g／m2第1、8天＋顺铂（DDP）75 mg/m2第2天至第4天治疗, GEM组接受GEM 1.25 g／m2第1、8天化疗。两组均治疗3周为1个周期，至少2个周期后按实体瘤疗效评价标准（RECIST）评价近期疗效及生存状况，评价不良反应。结果　GP组和GEM组治疗有效率分别为48.84 %（21／43）和35.71 %（15／42），差异无统计学意义（χ2＝1.708，P＝0.424）。GP组1年生存率39.53 %（17／43），2年生存率9.30 %（4／43），中位生存时间（MST）为11个月；GEM组1年生存率26.19 %（11／42），2年生存率7.14 %（3／42），MST为9个月， 两组中位生存时间比较差异无统计学意义（t＝1.377，P＝0.172）。GP组恶心、呕吐发生率（34.88 %）较GEM组（7.14 %）高，差异有统计学意义（χ2＝9.796，P＝0.002），其他不良反应两组接近，患者可耐受。结论　对于老年晚期NSCLC患者，GP方案和GEM单药化疗疗效相当，不良反应接近，GEM单药的胃肠道反应更轻。     

右肩关节疼痛活动受限

患者右肩关节隐痛5个月.活动受限2个半月入院,术前影像学检查见右肩胂颈部膨胀性骨质破坏,实验室检查：Hb：88g/L,球蛋白59.9g/L,尿蛋白（＋）;β2-微球蛋白和尿素均高于正常值.术中冰冻病理报告：恶性肿瘤,考虑为转移性低分化腺癌.术后行PET-CT检查,未找到明确原发灶.术后石蜡病理报告：桨细胞瘤,骨髓瘤临床表现多样,易发生误诊,应增加对比病的认识,提高警惕性,培养对临床资料的综合分析能力,拓宽诊断思路,达到对疾病的早期诊治,及时缓解临床症状,延长恶性肿瘤患者的生存期.     

Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial

PURPOSE: The primary objective of this randomized phase III study was to show significant difference in median time to progression (TTP) in patients with advanced NSCLC treated with single-agent gemcitabine maintenance therapy versus best supportive care following gemcitabine plus cisplatin initial first-line therapy. PATIENTS AND METHODS: Chemonaive patients with stage IIIB/IV NSCLC received gemcitabine 1,250 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day 1) every 21 days. Patients achieving objective response or disease stabilization following initial gemcitabine plus cisplatin therapy were randomized (2:1 fashion) to receive maintenance gemcitabine (1,250 mg/m(2) on days 1 and 8 every 21 days) plus best supportive care (GEM arm), or best supportive care only (BSC arm). RESULTS: Between November 1999 and November 2002, we enrolled 352 patients (median age: 57 years; stage IV disease: 74%; Karnofsky performance status (KPS) >80: 41%). Following initial therapy, 206 patients were randomized and treated with gemcitabine (138) or best supportive care (68). TTP throughout the study period was 6.6 and 5 months for GEM and BSC arms, respectively, while values for the maintenance period were 3.6 and 2.0 months (for p < 0.001 for both). Median overall survival (OS) throughout study was 13.0 months for GEM and 11.0 months for BSC arms (p = 0.195). The toxicity profile was mild, with neutropenia being most common grade 3/4 toxicities. CONCLUSION: Maintenance therapy with gemcitabine, following initial therapy with gemcitabine plus cisplatin, was feasible, and produced significantly longer TTP compared to best supportive care alone. Further studies are warranted to establish the place of maintenance chemotherapy in patients with advanced NSCLC.     

Relationship between expression of vascular endothelial growth factor in tumor tissue from gastric cancers and chemotherapy effects: comparison between S-1 alone and the combination of S-1 plus CDDP

BACKGROUND: We have reported that vascular endothelial growth factor (VEGF) expression in gastric cancers might be a selective marker between 5-fluorouracil (5-FU) and a combination of 5-FU plus cisplatin (CDDP). In this study, the relationship between VEGF expression and effects of S-1 with and without CDDP is investigated. METHODS: The subjects were 44 patients treated with S-1 (40 mg/m2, twice daily, days 1-28, repeated every 6 weeks) and 24 patients treated with S-1 plus CDDP (S-1 40 mg/m2, twice daily, days 1-21, CDDP, 60 or 70 mg/m2, day 8, repeated every 5 weeks). VEGF expression in pretreatment endoscopic biopsy samples was assessed immunohistochemically. RESULTS: Median survival times (MST) of the patients treated with S-1 and S-1 plus CDDP were 344 and 388 days. Among evaluable patients, the response rates of patients with VEGF (+) and (-) tumors to S-1 were 40% (6/15) and 54% (13/24), and to S-1 plus CDDP, 79% (15/19) and 80% (4/5). While the survival of patients with VEGF (-) tumors was slightly longer than those with VEGF (+) tumors in the S-1 group (MST, 425 versus 308 days, P = 0.42), patients with VEGF (+) tumors survived remarkably longer than those with VEGF (-) tumors in the S-1 plus CDDP group (MST, 570 versus 333 days, P = 0.19). CONCLUSION: Similarly to our previous study, it is suggested that the effects of adding CDDP to S-1 might be more remarkable in gastric cancer patients with VEGF (+) tumors than in those with VEGF (-) tumors. These results should be confirmed in a large phase III study.     

白蛋白结合型紫杉醇联合铂类药物对比吉西他滨联合铂类药物一线治疗中晚期肺鳞癌的临床疗效观察#br# #br#

目的观察白蛋白结合型紫杉醇联合铂类化疗药物对比吉西他滨联合铂类化疗药物一线治疗中晚期肺鳞癌患者的安全性和有效性。方法选择2016年6月至2021年3月徐州医科大学附属医院收治的68例存在手术禁忌证的中晚期肺鳞癌患者作为研究对象，根据化疗方案不同，分为白蛋白结合型紫杉醇联合铂类组（NAB P组）和吉西他滨联合铂类组（GEM组），分析两组患者的临床疗效及不良反应。结果NAB P组的客观缓解率为3056%，GEM组的客观缓解率为2813%，两组比较差异无统计学意义（P＞005）；NAB P组的疾病控制率为8611%，GEM组的疾病控制率为6563%，两组比较差异有统计学意义（P＜005）；不良反应方面， NAB P组的周围神经毒性、脱发、黏膜炎发生率高于GEM组（P＜005）；GEM组血小板降低的发生率高于NAB P组（P＜005）；NAB P组的无进展生存时间较GEM组长（P＜005），但1年生存率两组差异无统计学意义（P＞005）。结论白蛋白结合型紫杉醇联合铂类药物一线治疗中晚期肺鳞癌比吉西他滨联合铂类药物在疗效上更有优势，且NAB P组的不良反应轻，值得临床进一步推广。     

Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate.

PURPOSE: This phase III, randomized, open-label, multicenter study compared the overall survival associated with irinotecan plus gemcitabine (IRINOGEM) versus gemcitabine monotherapy (GEM) in patients with chemotherapy-naive, locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: IRINOGEM patients received starting doses of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 given weekly for 2 weeks every 3-week cycle. GEM patients received gemcitabine 1,000 mg/m2 weekly for 7 of 8 weeks (induction) and then weekly for 3 of 4 weeks. The primary end point of the trial was survival. Secondary end points included tumor response, time to tumor progression (TTP), changes in CA 19-9, and safety. RESULTS: In each arm, 180 randomly assigned patients comprised the intent-to-treat population evaluated for efficacy; 173 IRINOGEM and 169 GEM patients were treated. Median survival times were 6.3 months for IRINOGEM (95% CI, 4.7 to 7.5 months) and 6.6 months for GEM (95% CI, 5.2 to 7.8 months; log-rank P =.789). Tumor response rates were 16.1% (95% CI, 11.1% to 22.3%) for IRINOGEM and 4.4% (95% CI, 1.9% to 8.6%) for GEM (chi2 P <.001). Median TTP was 3.5 months for IRINOGEM versus 3.0 months for GEM (log-rank P =.352). However, subset analyses in patients with locally advanced disease suggested a TTP advantage with IRINOGEM versus GEM (median, 7.7 v 3.9 months). CA 19-9 progression was positively correlated with tumor progression. The incidence of grade 3 diarrhea was higher in the IRINOGEM group but grade 3 to 4 hematologic toxicities and quality-of-life outcomes were similar. CONCLUSION: IRINOGEM safely improved the tumor response rate compared with GEM but did not alter overall survival.     

Prognostic factors in patients with gemcitabine-refractory pancreatic cancer

OBJECTIVE: The purpose of this study was to identify prognostic factors in patients with gemcitabine-refractory pancreatic cancer and to determine criteria for selecting candidates for second-line treatment. METHODS: The records of 74 patients who were treated with gemcitabine (GEM) and followed up until disease progression were reviewed retrospectively. Sixteen clinical variables at the time of disease progression after GEM chemotherapy were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. RESULTS: At the time of analysis, 71 patients had died because of tumor progression. The overall median survival time was 5.1 months after first-line chemotherapy with GEM was initiated. Median survival time after disease progression was 2.0 months. Three factors, performance status, peritoneal dissemination and C-reactive protein level, were identified as independent prognostic factors in multivariate analysis. Median survival time in the good prognosis group (patients with performance status 0 or 1, no peritoneal dissemination and C-reactive protein <5.0 mg/dl) was 3.4 months. CONCLUSIONS: Performance status, serum level of C-reactive protein and peritoneal dissemination were identified as important prognostic factors in patients with GEM-refractory pancreatic cancer. These factors should be considered in determining the treatment following first-line chemotherapy in patients with advanced pancreatic cancer.     

Pilot study of combination 5-fluorouracil, cisdiamminedichloroplatinum II, and radiation therapy for grade III and IV astrocytomas

Nineteen patients with biopsy-proven high-grade astrocytomas received as initial treatment whole-brain radiation and combination chemotherapy with 5-fluorouracil (5-FU), 1,000 mg/m2/24 h as a continuous infusion for 96 h, and bolus cisdiamminedichloroplatinum II (CDDP), 100 mg/m2. Chemotherapy cycles were repeated on day 21, then every 28 days until progression or completion of six cycles. All 19 patients completed one cycle of chemotherapy. Toxicity was moderate, with cytopenias, nausea, vomiting, diarrhea, stomatitis, and reversible azotemia. Survival ranged from 2 to 160+ weeks, with a median of 35 weeks. The survival of the pilot group was compared with historical controls treated with radiation plus 1,3,-bis(2-chloroethyl)-1-nitrosourea (BCNU). Controls were similar in histology, age, performance score, and survival, without statistically significant differences. The combination of radiation therapy, continuous-infusion 5-FU, and bolus CDDP as described here for high-grade astrocytomas is moderately toxic and appears to offer no survival advantage compared with radiation therapy plus BCNU.     

体外化疗药物敏感实验对指导原发性肝癌个体化疗的临床意义

背景与目的:肝细胞癌(肝癌)化学治疗效果差。为了提高化疗效果,本研究采用体外化疗敏感实验——三磷酸腺苷肿瘤化疗药物敏感实验(adenosinetriphosphatetumorchemosensitivityassay,ATP鄄TCA)系统评估化疗药物,并利用该系统指导肝癌患者临床个体化疗。方法:获取50个原发性肝癌手术标本,采用ATP鄄TCA系统评估5鄄氟尿嘧啶(5鄄fluorouracil,5鄄FU)、丝裂霉素(mitomycin,MMC)、顺铂(cisplatin,DDP)、草酸铂(oxaliplatin,OXA)、表阿霉素(epirubicin,EPI)、健择(gemcitabine,GEM)、伊立替康(irinotecan,CPT鄄11)、足叶乙甙(etoposide,VP鄄16)和泰素(paclitaxel,PTX)等化疗药物;23例肝癌患者术后接受ATP鄄TCA系统指导临床化疗,同时以20例接受手术及常规治疗的肝癌患者作为对照,观察162周临床疗效。结果:ATP鄄TCA系统结果可评估率为90.8%。肝癌细胞对各种化疗药物中鄄高度敏感率分别为:泰素46%、伊立替康44%、健择36%、丝裂霉素14%、表阿霉素12%、顺铂8%、足叶乙甙6%、草酸铂6%以及5鄄氟尿嘧啶4%;临床结果:临床研究观察终点ATP鄄TCA组与对照组比较,PR、CR、SD及观察期内患者死亡率两组之间无显著性差异;然而对照组有较高病情进展发生率(60.00%vs.13.04%,P=0.003);ATP鄄TCA组较对照组在总病情缓解率(60.86%vs.30.00%,P=0.043)、平均手术后总生存期(78.91周vs.27.21周,P=0.006)及手术后无疾病进展生存期(30.52周vs.4.78周,P=0.005)方面表现出明显优势。结论:ATP鄄TCA系统可以成功用于评估肝癌标本。泰素、伊立替康和健择有较高的体外抗肝癌活性。ATP鄄TCA系统指导肝癌个体化疗有可能提高患者无疾病进展生存期和总生存期。     

Phase II study of cisplatin and 120-hour continuous infusion of 5-fluorouracil in patients with advanced pancreatic adenocarcinoma

BACKGROUND:: Advanced pancreatic carcinoma (APC) is a rapidly fatal diseaseand an active chemotherapy with palliative effects and impacton patient survival is needed. 5 fluorouracil (5-FU) combinedwith cisplatin (CDDP) has a recognized synergjstic activity,but its activity in APC has never been well established. METHODS:: Forty eligible patients (pts) with measurable APC were treatedin a phase II trial with 5-FU 1000 mg/m²/ day from day 1 today 5 by continuous intravenous infusion and CDDP 100 mg/m²on day 2. Eighty percent of the pts (36/40) had metastatic disease,32.5% (13/40) were previously treated and 65% (26/40) had performancestates of 2 or 3. RESULTS:: Of 38 evaluable pts, one had a complete response and 9 achievedpartial responses; the overall response rate (RR) was 26.5%(95% CI: 12% to 40%). The median duration of responses was 10months (range 4-18). The RR in non-pretreated pts was 32% Apalliative effect was seen in 45% of pts (17/38). The mediansurvival was 7 months and 12 pts (29%) were alive at 1 year.Leukopenia was the most important toxicity; 11 pts (27%) hada grade 4 leukopenia and 3 had neutropenic fever. CONCLUSIONS:: The combination of CDDP and 5-FU in continuous infusion seemsan active and well tolerated treatment in APC and will be comparedto standard therapy in a multicentric randomized trial. pancreatic cancer, chemotherapy, 5-fluorouracilcisplatin combination     

Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101).

BACKGROUND: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations. PATIENTS AND METHODS: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m(2) on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m(2) on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles. RESULTS: A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens. CONCLUSIONS: Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile.