吉西他滨/卡铂和吉西他滨/顺铂方案治疗晚期非小细胞肺癌的疗效比较

目的 观察吉西他滨／卡铂（GCarb）和吉西他滨／顺铂（GCis）治疗晚期非小细胞肺癌（NSCLC）的疗效和毒副反应。方法 经病理和细胞学证实的40例晚期NSCLC患者随机分为两组。GCarb组给予吉西他滨1000mg/m^2静脉滴注，第1、8天；卡铂AUC4－6静脉滴注，第1天。GCis组给予吉西他滨1000mg/m^2静脉滴注，第1、8天，顺铂30－40mg/m^2静脉滴注，第1－3天。两组均21天为一周期，连续使用2－3周期评价疗效和毒副反应。结果 GCarb组有效率为65％，GCis组为60％，两组疗效无显著性差异（P＞0.5）。两组毒副反应依次为骨髓抑制、胃肠道反应、脱发和皮疹。GCarb组胃肠道反应低于GCis组（P＜0.05）。结论 GCarb和GCis均可作为NSCLC的一线治疗方案。     

多西紫杉醇联合吉西他滨治疗晚期非小细胞肺癌的临床观察

目的:观察非铂类药物多西紫杉醇(艾素)和吉西他滨(泽菲)联合治疗晚期非小细胞肺癌(NSCLC)的临床疗效及不良反应。方法:37例NSCLC给予泽菲1 000mg/m2,第1天和第8天静脉滴注30min,艾素75mg/m2,第8天静脉滴注1h,21d为一个周期,至少治疗2个周期。结果:全组33例可评价疗效,CR 1例,PR 11例,总有效率为39.4%(CR+PR),SD45.5%(15/33),PD18.2%(6/33),中位生存期为11个月,疾病进展时间为6.5个月;1年生存率为48.5%(16/33)。不良反应主要是骨髓抑制,其中Ⅲ~Ⅳ度白细胞下降有31.4%,Ⅲ~Ⅳ度血小板下降有23.5%;非血液学毒性表现为恶心及呕吐,Ⅰ~Ⅱ度有23.1%,无Ⅲ~Ⅳ度恶心及呕吐。结论:多西紫杉醇联合吉西他滨对于晚期NSCLC疗效较理想,不良反应较低,对于提高生活质量有意义,是可以替代铂类药物的有效方案。     

吉西他滨对非小细胞肺癌细胞株A-549放疗增敏的机制

目的:研究吉西他滨(GEM)对体外培养非小细胞肺癌细胞的细胞周期改变和凋亡影响,及其放疗增敏的作用及机制。方法:体外培养非小细胞肺癌细胞株A-549,分单纯培养细胞组、单纯照射组、单纯吉西他滨组及吉西他滨联合放疗组(联合放疗组);单纯照射组采用源皮距(SSD)为100 cm,剂量2 Gy,6 MV光子线照射;吉西他滨组采用MTT法选择对细胞生长抑制率≤10%的药物浓度(IC10)即为GEM的最佳实验浓度;联合放疗组采用最佳实验浓度的GEM加上述同等条件的照射剂量和方法;流式细胞仪分析上述各组细胞的细胞周期和凋亡率。结果:经MTT法检测显示,GEM在0.020-0.030μmol/L之间时为最佳实验浓度。流式细胞仪分析各处理组细胞的细胞周期和凋亡率结果表明,各处理组之间细胞在S期时的比例有显著差异(P<0.05),G2/M、S期比值变化最为明显;细胞凋亡率亦有统计学差异(P<0.05);单纯采用GEM浓度为0.02,0.03μmol/L时没有明显差别(P>0.05)。结论:吉西他滨可以具有放射增敏和协同作用,其机制可能与吉西他滨能改变A-549细胞生长周期并诱导其凋亡有关。     

吉西他滨联合顺铂治疗鼻咽癌远处转移的临床研究

目的观察吉西他滨联合顺铂治疗鼻咽癌远处转移的临床疗效和不良反应。方法吉西他滨1000mg/m2,分别于第1天和第8天静脉点滴,顺铂30mg/m2,第1～3天,21天为1个周期,所有病例接受至少2个周期的化疗。结果32例患者入组,完全缓解7例,部分缓解21例,总有效率为87.5%(28/32)。主要不良反应为骨髓抑制、恶心、呕吐、脱发及皮疹,有4例(12.5%,4/32)发生了Ⅲ～Ⅳ度骨髓毒性。结论吉西他滨联合顺铂方案治疗鼻咽癌远处转移有较好的疗效,患者耐受性良好,值得临床进一步研究。     

Phase I-II study of gemcitabine and paclitaxel in pretreated patients with stage IIIB-IV non-small cell lung cancer

Gemcitabine and paclitaxel are among the most active new agents in non-small cell lung cancer (NSCLC) and are worth considering for second-line chemotherapy. In this phase I–II study, we combined gemcitabine and paclitaxel for second-line treatment of advanced NSCLC. Gemcitabine doses were kept fixed at 1000 mg/m² on day 1 and 8, and paclitaxel doses were escalated from 90 mg/m² on day 1 of the 21-day cycle. Thirty-seven patients were treated at six different dose levels. Grade 4 neutropenia was dose-limiting toxicity (DLT), since it occurred in two out of six patients treated at paclitaxel 240 mg/m²; the paclitaxel dose level just below (210 mg/m²) was selected for phase II evaluation. Non-hematologic toxicity was mild. One complete response (CR) (3%) and 13 partial responses (PR) (36%) were observed in 36 evaluable patients for an overall response rate of 39% (95% C.I., 23–57%). Median duration of response was 35 weeks (range, 8–102). All of the observed objective responses occurred in the 19 patients who had previously responded to the first-line therapy. Median survival was 40 weeks (range, 8–108 weeks). The combination of gemcitabine and paclitaxel is a feasible, well-tolerated, and active scheme for second-line treatment of advanced NSCLC; further evaluation, at least in selected patients, such as those previously responding to first-line chemotherapy, is definitely warranted.     

Effects of gemcitabine on cell proliferation and apoptosis in non-small-cell lung cancer (NSCLC) cell lines

We evaluated the antiproliferative and the proapoptotic ability of gemcitabine in three non-small-cell lung cancer (NSCLC) cell lines. NCI-H292 (mucoepidermoid carcinoma), NCI-CorL23 (large-cell carcinoma) and NCI-Colo699 (adenocarcinoma) cells were cultured with and without 0.5, 0.05 and 0.005 μM gemcitabine for 24, 48 and 72 h, respectively. Gemcitabine exerted a stronger and earlier antiproliferative and proapoptotic effect on H292 cells than on CorL23 or Colo699 cells. Fas receptor expression was increased in all three cell lines and was higher in Colo699 than in CorL23 cells. The incubation of NSCLC with anti-Fas agonistic monoclonal antibody (CH11) induced cell apoptosis in H292 cells, demonstrating that the Fas receptor was functionally active. Finally, gemcitabine and CH-11 exerted a synergistic effect on cell apoptosis in H292 cells. This study demonstrates that gemcitabine induces apoptosis in NSCLC and that this effect might be exerted by modulating functionally active Fas expression, and these effects of gemcitabine were stronger in H292 cells than in either CorL23 or Colo699 cells. Received: 24 March 1999 / Accepted: 25 July 2000     

Gemcitabine and cisplatin in advanced nasopharyngeal carcinoma: a pilot study

A pilot study was performed to evaluate the efficacy and safety of gemcitabine and cisplatin combination in the treatment of patients with metastatic nasopharyngeal carcinoma (NPC). Eligible patients were those with metastatic NPC who had been treated with radiotherapy and cisplatin plus 5-fluorouracil chemotherapy. Cisplatin was given intravenously at the fixed dose of 30 mg/m² on days 1-3. Gemcitabine was intravenously administered over 30 min infusion with the dose escalated from 800 to 1200 mg/m² on days 1 and 8. The 3-week schedule defined a cycle of treatment. Fifteen patients were enrolled and assessed for the worst toxicities. For a total of 83 cycles, Grade 3-4 toxicity was 46.7% for neutropenia, 40.0% for thrombocytopenia, and 20.0% for anemia. Grade 3 nonhematologic toxicity was 13.3%. Fourteen patients were assessable for response. The overall response rate was 92.9%, with complete response in three patients (21.4%). Median survival was 10.2 months. Seven patients had lived more than one year, and two patients had lived more than 2 years. The recommended dose of gemcitabine was 1000 mg/m² on days 1 and 8 in each cycle. In conclusion, the present combination is well tolerated and highly active in the treatment of advanced NPC patients.     

Phase II study of gemcitabine plus paclitaxel in metastatic breast cancer patients with prior anthracycline exposure

Chemotherapy provides palliation and modest prolongation of symptom-free survival in metastatic breast cancer. Taxane containing regimens are commonly considered to be among the initials in metastatic setting due to earlier use of anthracyclines in the course of breast cancer. Therefore, we conducted this Phase II study to assess efficacy and safety of gemcitabine plus paclitaxel (GT) combination therapy in anthracycline pretreated metastatic first-line setting. Patients and Methods: The study enrolled 26 women with pathologically confirmed and measurable metastatic breast cancer who were previously treated with anthracycline but no prior chemotherapy for metastatic disease. Twenty six and twenty four patients were eligible for toxicity and efficacy evaluations respectively. Mean age was 47.3 years and median ECOG performance status was 0. Twenty patients (76.9 percent) had visceral metastases, most commonly located in liver and lung. Treatment schedule was as follows: paclitaxel 175 mg/m² was administered intravenously in 3 hours on Day 1 and gemcitabine 1000 mg/m² was administered intravenously in 30 minutes on Day 1 after paclitaxel application, and on Day 8 every 21 days. Results: Objective response rate was 41.7 percent (95 percent CI: 21.9-61.4) with 16.7 percent (95 percent CI: 1.7-31.6 percent) CR, and 25.0 percent (95 percent CI: 7.6-42.3 percent) PR. Median time to progression and overall survival were 9.6 and 14.5 months, respectively. Grade 3-4 toxicity was observed in 34.6 percent (9) patients. Treatment of two patients was discontinued due to toxicity, consisting of Grade 3 hypersensitivity reactions and Grade 4 infections in one patient each. Dose reductions due to myelotoxicity were performed in 4 (15.3 percent) patients. Hematologic toxicities were generally manageable with appropriate dose modifications and supportive care. Conclusion: Gemcitabine and paclitaxel combination regimen is effective and has manageable toxicity profile as first line metastatic setting.     

Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver

AIM: In nonresectable cholangiocellular carcinoma (CCC) therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%. Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver. METHODS: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m2) and additional transarterial chemoembolization procedures (50 mg/m2 cisplatin, 50 mg/m2 doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity. RESULTS: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO Ⅲ/Ⅳ) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered. Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases, stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo. CONCLUSION: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.     

Response of combination platinum and gemcitabine chemotherapy for recurrent epithelial ovarian carcinoma

OBJECTIVE: It has been postulated that gemcitabine inhibits DNA repair, and platinum resistance is due to increased DNA repair activity. The addition of gemcitabine to platinum-based agents may have synergistic tumoricidal activity. METHODS: Retrospective chart review of all patients with recurrent, persistent, or progressive fallopian tube or ovarian carcinoma treated with a platinum-based compound and gemcitabine from 2001 to present was performed. RESULTS: Twenty-nine patients on second to eight line chemotherapy met inclusion criteria. The median age was 53 years. Twenty-two patients received cisplatin and gemcitabine, and 7 patients received carboplatin and gemcitabine based on results of chemoresistance assays or prior chemorelated toxicities. The intent to treat was with six cycles of gemcitabine (1000 mg/m(2)) and either cisplatin (75 mg/m(2)) or carboplatin (AUC 5) day 1 and gemcitabine only on day 8 of a 21-day cycle. The median number of cycles administered was six. There were 20 grade 3 and 4 toxicities and 63% of patients by cycle 6 needed erythropoietin marrow support and 19% needed GCSF support by cycle 4. Twenty-one patients required discontinuation of day 8 that most commonly occurred at cycle 4. Eleven (38%) had CR, 5 (17%) had PR, 6 (21%) had SD, and 7 (24%) had PD, which is a 55% overall response. Nineteen of 29 patients (66%) showed platinum resistance to initial therapy. Of those, four (21%) had CR, four (21%) had PR, six (32%) had SD, and five (26%) with PD, which demonstrates a 42% overall response rate for this particular subset of patients. CONCLUSIONS: Adjuvant combination platinum-based agent with gemcitabine is a very effective and well-tolerated treatment for recurrent fallopian tube or ovarian carcinoma; even in those who exhibit initial platinum resistance.