吉西他滨联合顺铂与去甲长春碱联合顺铂治疗晚期非小细胞肺癌的临床研究

目的 观察比较吉西他滨联合顺铂(GC方案)与去甲长春碱联合顺铂(VC方案)治疗晚期非小细胞肺癌的疗效、生存率及毒副反应。方法 对67例经病理或细胞学证实的晚期非小细胞肺癌患者给予联合化疗，GC方案32例，VC方案35例，两组病例具有可比性。吉西他滨1000～1250mg／m^2，静脉滴注第1、8天，顺铂80～100mg／m^2，静脉滴注第1～3天，去甲长春碱25mg／m^2，静脉滴注第1、8天，21天为一个周期，每例患者治疗2周期以上。结果 GC组总有效率37．5％，1年生存率38．7％，中位生存期9．5个月；VC组总有效率34．3％，1年生存率34．3％，中位生存期8．6个月。两组间有效率、1年生存率比较差异均无显著性(P=0．59，P=0．48)。最常见的毒副反应为骨髓抑制，GC组Ⅲ～Ⅳ度血小板减少发生率显著高于VC组(P=0．015)，而VC组Ⅲ～Ⅳ度白细胞减少发生率显著高于GC组(P=0．01)。结论 吉西他滨联合顺铂和去甲长春碱联合顺铂治疗NSCLC，疗效肯定，毒性均可耐受。两方案疗效无显著性差异。     

吉西他滨联合顺铂治疗复发或转移性鼻咽癌的临床研究

目的 观察吉西他滨联合顺铂治疗复发或转移性鼻咽癌的临床疗效和不良反应。方法 吉西他滨1000mg／m^2，分别于第1天和第8天静脉点滴；顺铂80mg／m^2,第1天，或顺铂每天20mg／m^2,第1-4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 28例患者入组，完全缓解6例，部分缓解18例，总有效率为85．7％（24／28）。中位随访时间15个月（6～23个月），1年生存率为86％，中位疾病进展时间为8．6个月（2．5～18个月）。主要不良反应为骨髓抑制及恶心、呕吐，有4例（14％，4／28）发生了Ⅲ～Ⅳ度骨髓毒性。结论 吉西他滨联合顺铂方案治疗复发或转移性鼻咽癌有较好的疗效，患者耐受性好，值得临床进一步研究。     

Gemcitabine and cisplatin for advanced urothelial carcinomas: the Ehime University Hospital experience

Background The aim of this study was to evaluate the efficacy and safety of a combined chemotherapy regimen, gemcitabine and cisplatin (GC), in the treatment of advanced urothelial carcinomas. Methods Fifty-five patients with advanced urothelial cancer were treated with GC (gemcitabine 1000 mg/m² on days 1, 8, and 15; cisplatin 70 mg/m² on day 2) every 28 days. The median follow-up was 30 months (range, 3 to 57 months). Results With the GC therapy, 35 of the 55 patients (63.6%) showed an objective response, with 7 (12.7%) achieving a clinical complete response (CR) and 28 (50.9%), a partial response (PR). GC therapy had a better impact on metastases in the lung and lymph nodes than on metastases in the liver and bone. Lung and lymph nodes showed objective responses of 64.7% and 65.8%, respectively. Eight of the 20 patients (40.0%) who had previously been treated with other regimens showed an objective response, with 1 achieving a CR and 7 achieving a PR. In the 47 patients with metastasis, the median time to progression was 7.0 months (range, 2 to 49 months), and the median overall survival was 12.0 months (range, 3 to 49 months). The 2-year survival rate was 80.0% in the CR group, while it was 55.1% in the PR group and 10.0% in the progressive disease (PD) group. The toxicities associated with GC, particularly mucositis, anorexia, and alopecia, were quite mild. Grade 3–4 toxicity was primarily hematological, including anemia (27.3%), neutropenia (32.7%), and thrombocytopenia (43.6%). Conclusion GC is considered to be a highly effective and well-tolerated regimen for the treatment of advanced urothelial carcinomas, with moderate toxicity.     

国产吉西他滨联合顺铂治疗晚期卵巢癌的临床研究

目的:探讨国产吉西他滨(泽菲)联合顺铂治疗晚期卵巢癌的疗效及毒性反应。方法:泽菲1000mg/m2静脉滴注超过30分钟,第1、8天,顺铂30mg/m2静脉滴注超过3小时,第1~3天,化疗前30分钟推注康泉预防消化道反应,每2天重复1次,至少2疗程,治疗至疾病进展或出现不能接受的毒性反应,最多6疗程,每2疗程后评价疗效,复查包括妇科检查、胸腹CT、血CA125。随访30个月。结果:31例转移性卵巢癌共完成疗程数为123个,每个患者接受治疗2~6个疗程,平均4个疗程,随访率100%,获得CR2例,PR13例,有效率48·39%,生存质量明显提高。结论:泽菲联合顺铂对于晚期卵巢癌患者是有效的,毒性反应可以耐受,值得临床进一步研究。     

Induction chemotherapy with cisplatin and epirubicin followed by radiotherapy and concurrent cisplatin in locally advanced nasopharyngeal carcinoma observed in a non-endemic population

Background and purpose

Chemoradiotherapy (CRT) represents the main therapy choice in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). The aim of this study was the clinical evaluation of neoadjuvant chemotherapy (NACT) followed by CRT in a non-endemic population affected by advanced NPC.

Materials and methods

Patients with locoregionally advanced NPC were treated with three cycles of induction chemotherapy (CHT) with cisplatin (100 mg/m²) plus epirubicin (90 mg/m²), followed by cisplatin (100 mg/m²) and concomitant radiotherapy (70 Gy).

Results

In 40 patients treated with such protocol, after the completion of induction CHT and CRT we observed the objective response rates of 90% and 100%, respectively. Treatment tolerability and toxicity were easily controllable. With a median follow-up time of 54 months, 3- and 5-year disease-free survival was 75% and 65% and 3- and 5-year overall survival was 84% and 77%.Three- and 5-year locoregional control was 82% and 70%, and 5-year distant metastases free survival was 75%.

Conclusions

NACT with cisplatin and epirubicin followed by concomitant CRT represents a feasible, efficient treatment for patients with advanced NPC. This regimen ensures an excellent locoregional disease control and overall survival with a low incidence of distant metastases.     

顺铂加阿霉素同期化疗治疗晚期鼻咽癌的临床研究

目的：观察顺铂、阿霉素同期化放疗治疗局部晚期鼻咽癌的疗效及毒副反应,探讨该方案的临床可行性。方法：３２例Ｔ３－４Ｎ２－３Ｍ０局部晚期鼻咽癌患者进入综合治疗组,分别在放疗第１、２２、４３ｄ接受顺铂７０ｍｇ／ｍ＾２＋阿霉素３０ｍｇ／ｍ＾２同期化疗,化疗当天及第二天水化利尿。另配对选取３２例单纯放疗者为对照组。结果：所有病例如期完成治疗。放疗４０Ｇｙ时,综合组颈淋巴结有效率较高（Ｐ〈０．０５）;放疗结束     

Fixed dose-rate infusion of gemcitabine in combination with cisplatin and UFT in advanced carcinoma of the pancreas

Background: Gemcitabine is currently considered the standard treatment for advanced pancreatic cancer (APC). Cisplatin and a fluoropyrimidine have some activity in the treatment of this cancer. The aim of this trial is to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with cisplatin and UFT in patients with APC. Patients and methods: Forty-six chemotherapy-naïve patients with APC that was either unresectable or metastatic were included in this phase II study. All of them had Karnofsky performance status ≥50 and unidimensionally measurable disease. Treatment consisted of gemcitabine 1,200 mg/m² given as a 120-min infusion weekly for three consecutive weeks, cisplatin 50 mg/m² on day 1 and oral UFT 400 mg/m²/day (in two to three daily doses) on days 1 to 21; cycles of treatment were given every 28 days. Results: A total of 208 cycles of chemotherapy were given with a median of 4 per patient. Fourteen patients (30%) achieved partial responses (95% CI 19–48%) and 17 (37%) had stable disease. The median time to progression was 5 months, and the median overall survival 9 months. Nineteen patients (49%; 95% CI 32–64%) had a clinical benefit response. Grade 3–4 WHO toxicities were as follows: neutropaenia in 26 patients (57%), with 5 cases of febrile neutropaenia (11%), thrombocytopaenia in 15 (33%), anaemia in six (13%), diarrhoea in 5 (11%), asthenia in 2 (4%) and mucositis in 1 (2%). Seven patients required hospitalisation for treatment-related complications. Conclusion: A fixed dose-rate infusion of gemcitabine associated with cisplatin and UFT is active in patients with APC, though at the cost of considerable toxicity.     

Gemcitabine improves survival in patients with recurrent or metastatic nasopharyngeal carcinoma

For decades, the selection of chemotherapeutic regimens for the treatment of recurrent or metastatic nasopharyn-geal carcinoma has been mainly empirical. To our knowledge, there is no phase 3 trial that has been conducted to determine the optimal treatment for these patients before our publication. Recently, we published an article inThe Lancet entitled “Gemcitabine plus cisplatin versus lfuorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial.” The results of our study indicate that gemcitabine plus cisplatin could improve the survival of patients with recurrent or metastatic nasopharyngeal carcinoma com-pared with conventional lfuorouracil plus cisplatin.     

Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy

Purpose This study was designed to evaluate the anti-tumor activity and toxicity profile of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma (NPC) who had been pretreated with platinum-based chemotherapy. Method This is an open label, single arm phase II trial. All patients were treated with single agent of gemcitabine. Gemcitabine was given in the dosage of 1.0 g/m² on days 1, 8, 15, each cycle repeated every 4 weeks. Gemcitabine was added to 100 ml normal saline infused over 30 min. Result About 32 patients were enrolled in this trial. Thirty patients were assessable for response to treatment. Fourteen patients had a partial response (PR), giving an overall response rate of 43.8% (14/32); 9 patients had stable disease (28.1%) and 7 progressed disease (21.9%). The median time to progression was 5.1 months and median survival time was 16 months, 1 year survival rate was 67%, 2 year overall survival rate was 12%. A total of 11 patients (34.4%) experienced grade 3 and 4 toxicity and the main toxicity was myelosuppression. the non-hematology toxicity was minimal. Conclusion The effectiveness of gemcitabine was higher and side effects were minimal in advanced NPC patients after platinum-based chemotherapy failed. This paper was presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, 2004.     

Locally advanced nasopharyngeal carcinoma: Current and emerging treatment strategies

Although nasopharyngeal carcinoma (NPC) is a widespread malignant tumor, it is particularly frequent in Southeast Asia. Although T1 tumors can be effectively controlled with exclusive radiotherapy, this treatment modality is insufficient for most NPC patients, who present with locally advanced disease at diagnosis. In fact, for stages ranging from T2b N0 to T4 N3, definitive scientific evidence supports the use of concurrent platinum-based chemotherapy with standard external beam radiotherapy. This treatment approach has shown a statistically significant advantage in terms of overall survival, with respect to radiotherapy alone. Several trials have also investigated the use of neoadjuvant and adjuvant chemotherapy in combination with radiotherapy or chemo-radiotherapy. Platinum compounds, anthracyclines and taxanes are among the chemotherapy agents employed. This review focuses on the clinical results obtained in the field of adjuvant/concurrent/neoadjuvant chemotherapy for locally advanced NPC, for which exclusive concurrent chemo-radiotherapy currently represents the standard treatment approach.     

吉西他滨联合顺铂治疗晚期原发性肝癌的临床观察

目的观察吉西他滨（商品名健择）联合顺铂化疗治疗晚期原发性肝癌的疗效及毒副反应。方法34例失去手术机会的晚期肝癌患者,给予GP方案化疗四个周期,观察其疗效及毒副反应。结果CR 1例、PR 9例,MR10例,SD8例,PD6例,RR 29．4%（10/34）。45．8%（11/24）的病人AFP较治疗前基线下降超过50%。21例疗前有肝区疼痛的患者,疼痛全部于化疗两个周期后消失。不良反应主要为骨髓抑制,Ⅲ-Ⅳ度白细胞减少为17．6%（6/34）,Ⅲ-Ⅳ度血小板减少为14．7%（5/34）;非血液学毒性方面,除少数病人有轻度恶心外,胆红素、转氨酶升高均不超过正常值上限1．5倍,尿素氮、肌酐未发现有明显升高。临床获益患者中位TTP4．5个月,MST12．8个月,一年生存率60．7%。结论GP方案化疗治疗晚期肝癌具有较好的客观疗效,副反应轻,能明显减轻病人的痛苦,延长病人的生命,值得进—步探讨、研究。     

GC方案治疗晚期尿路上皮癌近期疗效评价

目的观察吉西他滨联合顺铂（Gemcitabine＋Cisplatin,GC）方案治疗晚期尿路上皮癌的近期疗效和不良反应。方法21例尿路上皮癌患者均经病理证实,其中膀胱癌17例,输尿管癌3例,肾盂癌1例。化疗前肝肾功能和血常规检测均正常。全身化疗方案：吉西他滨1000mg／m。,静脉滴注30rain,第1、8天各1次;顺铂70mg／m^2,充分水化,静脉滴注30～60min,第1天。21d为一个疗程。每个疗程结束评价疗效及毒副反应。结果完成1个周期11例,2个周期4例,3个周期4例,4个周期2例。近期疗效：完全缓解（CR）0例,部分缓解（PR）10例,稳定（SD）6例,进展（PD）5例,总有效率47．6％。主要不良反应为骨髓抑制和消化道反应,多为轻中度。无治疗相关性死亡病例。结论吉西他滨联合顺铂（GC）方案是治疗晚期尿路上皮癌的有效方法,患者耐受性好。     

A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients

To evaluate the role of adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma (NPC) patients, we conducted a randomized Phase III trial comparing radiotherapy (RT) followed by adjuvant chemotherapy to RT alone in patients with advanced NPC.

Between November 1994 and March 1999, 157 patients with Stage IV, M₀ (UICC/AJCC, 1992) advanced NPC disease were randomized to receive standard radiotherapy, as follows: 35–40 fractions, 1.8–2.0 Gy/fraction/day, 5 days/week, to a total dose 70–72 Gy with or without 9 weekly cycles of 24-h infusional chemotherapy (20 mg/m² cisplatin, 2,200 mg/m² 5-fluorouracil, and 120 mg/m² leucovorin) after RT. Of 157 patients enrolled, 154 (77 radiotherapy, 77 combined therapy) were evaluable for survival and toxicity analysis.

With a median follow-up of 49.5 months, the 5-year overall survival and relapse-free survival rates were 60.5% vs. 54.5% (p = 0.5) and 49.5% vs. 54.4% (p = 0.38) for the radiotherapy-alone group and the combined radiotherapy and adjuvant chemotherapy group, respectively. The Cox regression showed that the hazard rates ratio of combined treatment to RT alone was 0.673 (p VALUE = 0.232); the 95% confidence interval was 0.352 and 1.288, respectively. Patients who received combined treatment had a lower systemic relapse rate than radiotherapy-alone patients, according to relapse pattern analysis. The incidence of leukopenia (≥ Grade 3) occurred in 17 out of 819 (2.1%) cycles of weekly chemotherapy. No patient developed moderate to severe mucositis (≥ Grade 3).

We conclude that adjuvant chemotherapy after RT for patients with advanced NPC has no benefit for overall survival or relapse-free survival.     

PPF方案化疗加放疗治疗中晚期鼻咽癌近期疗效观察

目的 :观察PPF方案 (顺铂、平阳霉素和 5 氟脲嘧啶 )联合化疗加放疗治疗Ⅲ、Ⅳ期鼻咽癌的近期疗效。方法 :46例Ⅲ、Ⅳ期鼻咽癌患者随机分成两组 ,观察组 2 3例采用放疗加同步联合化疗 ;对照组 2 3例单纯放疗。结果 :观察组治疗后6个月内鼻咽肿物完全消退率为 86 96 %(2 0 / 2 3) ,颈部淋巴结转移灶完全消退率为 94 74%(18/ 19) ,对照组分别为 6 0 86 %(14/ 2 3)和 6 1 90 %(13/ 2 1) ,经统计学检验差异具有显著性意义 (P <0 0 5 ) ,而毒副作用相似。结论 :放疗同步进行化疗能提高Ⅲ、Ⅳ期鼻咽癌近期疗效。     

Phase II study of capecitabine and cisplatin combination as first-line chemotherapy in Chinese patients with metastatic nasopharyngeal carcinoma

PURPOSE: Cisplatin combined with 5-fluorouracil (5-Fu) is widely used in the management of advanced nasopharyngeal carcinoma (NPC). However, catheters and pumps are necessary for the continuous infusion of 5-Fu, which add to the cost, immobility and inconvenience of treatment. Capecitabine, an oral fluoropyrimidine, is a potentially more active and more convenient substitute to 5-Fu. A phase II study was conducted to evaluate the efficacy and safety of a capecitabine and cisplatin combination in metastatic NPC. PATIENTS AND METHODS: In the multicenter, open-label, single-arm phase II study, patients with metastatic NPC who previously received no palliative chemotherapy were enrolled. Patients received oral capecitabine (1,000 mg/m(2) twice daily from day 1 to 14) and intravenous cisplatin (80 mg/m(2), day 1) every 3 weeks. RESULTS: A total of 48 patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. There were 3 patients (6.3%) with complete response and 27 patients (56.3%) with partial response, giving an overall response rate of 62.5% (95% CI, 49.1-76.4%). The median duration of response in the 30 responding patients was 7.5 months (range 1.4-22.4 months). With a median follow-up period of 13.3 months (range 2.3-50 months), the median time to progression and median overall survival for all patients were 7.7 months (95% CI, 6.3-9.2 months) and 13.3 months (95% CI, 9.4-17.2 months), respectively. Toxicities were moderate and manageable. Grade 3/4 toxicities included neutropenia (14.6%), anemia (4.2%) and thrombocytopenia (2.1%), nausea (8.3%), vomiting (10.4%), diarrhea (8.3%), stomatitis (6.3%) and hand-foot syndrome (HFS) (4.2%). CONCLUSIONS: The combination of capecitabine and cisplatin is active and well tolerated as a first-line therapy for patients with metastatic NPC.     

吉西他滨联合卡铂用于晚期鼻咽癌二线治疗的临床观察

 目的 观察吉西他滨（泽菲国产吉西他滨）联合卡铂的联合方案治疗晚期复治鼻咽癌的近期疗效及毒性反应。方法 32例均为一线含顺铂方案化疗失败的晚期鼻咽癌病人。吉西他滨1000mg／m²，d1.8；卡铂400mg／m²，d1；21天为1周期。完成2周期后评价疗效及毒性。结果 32例中CR4例，占12．5％；PR16例，占50．0％；总缓解率（CR＋PR）62．5％。SD8例（25％），PD4例（12．5％）。中位缓解时间4．5个月。骨髓抑制为主要毒性：Ⅲ／Ⅳ度白细胞下降为43．6％，4例合并感染发热；Ⅲ／Ⅳ度血小板下降为21．8％。胃肠道反应轻微。结论 吉西他滨与卡铂的联合方案对一线含顺铂方案化疗失败的晚期鼻咽癌有较高的缓解率，毒性反应轻，值得作为二线方案推广使用。     

健择、顺铂方案与诺维本、异环磷酰胺、顺铂方案治疗晚期非小细胞肺癌临床对比研究

目的　观察健择 (GEM )、顺铂 (DDP)组成的GP方案和诺维本 (NVB)、异环磷酰胺 (IFO)、DDP组成的NIP方案治疗非小细胞肺癌的疗效和安全性。方法　 80例Ⅲ～Ⅳ期NSCLC患者分为两组 ,每组 40例。一组予以GP方案 :GEM 10 0 0mg/m2 ,第 1、8或 15天 ;DDP 70～ 80mg/m2 ,第 1天。另一组予以NIP方案 :NVB 2 5mg/m2 ,第 1、8天 ;IFO 1.2g/m2 ,第 1～ 4天连续给药 ;DDP 70～ 80mg/m2 ,第 1天。结果　GP组和NIP组有效率分别为 40 .0 %和 5 2 .5 % ,无统计学差异。GP组和NIP组中位生存期分别为 13 .68个月和15 .3 4个月 ,1年生存率分别为 5 4.2 9%和 5 9.46% (P >0 .0 5 )。Ⅲ～Ⅳ度白细胞减少发生率GP组和NIP组分别为 2 7.5 %和 5 5 .0 % (P <0 .0 5 )。非血液毒性反应GP组大多低于NIP组 (P <0 .0 5 )。结论　三药联合化疗方案虽然在疗效上略高于两药联合化疗方案 ,但无显著性差异 ,却增加了毒副反应。两药联合化疗方案GP是治疗晚期NSCLC患者的有效方案。而对于年纪较轻、一般情况较好的患者可予以NIP方案     

吉西他滨联合顺铂治疗晚期非小细胞肺癌临床研究

目的：观察吉西他滨联合顺铂治疗晚期非小细胞肺癌的疗效及毒副反应。方法：经病理组织学或细胞学证实的43例晚期非小细胞肺癌患者给予吉西他滨1000mg/m2静滴,第1,8,15天,顺铂30mg/m2静滴,第1－3天,28天为一周期,或吉西他滨1200mg/m2静滴,第1,8天,顺铂30mg/m2静滴,第1－3天,21天为一周期,结果：全组CR1例,PR20例,SD13例,PD9例,总有效率48．8％,初治病例有效率为62．5％,复治病例为31．6％,两组间差异具有显著性（P＜0．05）,毒副反应以白细胞及血小板下降为常见,但均可耐受,结论：吉西他滨联合顺铂治疗晚期非小细胞肺癌具有较好的疗效。毒性可以耐受。     

健择加顺铂联合治疗晚期非小细胞肺癌近期疗效观察

目的 观察健择(GEM,Gemcitabine,Gemzer,吉西他滨)与顺铂(DDP,Cisplatin)联合化疗方案治疗晚期非小细胞肺癌(NSCLC)的临床疗效及毒副反应。方法 36例均为Ⅲ、Ⅳ期非小细胞肺癌患者。健择1000 mg/m~2静滴d1,d8,顺铂40 mg静滴d1～d3,21d为1个周期,治疗2～3周期。结果 总有效率为44.4％(均为部分缓解)。主要毒副反应为Ⅱ～Ⅲ度骨髓抑制及恶心呕吐。骨髓抑制主要表现为血红蛋白、白细胞及血小板的降低,但没有严重的Ⅲ～Ⅳ度损害。无明显的肝肾功能的损害。无一例因毒性反应而延期化疗者。结论 健择加顺铂联合化疗方案治疗晚期非小细胞肺癌有较好的疗效,且耐受性较好。     

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。