吉西他滨联合卡培他滨治疗铂类方案失败的晚期鼻咽癌的临床研究

目的:观察吉西他滨联合卡培他滨治疗铂类方案失败的晚期鼻咽癌的临床疗效和毒副反应。方法:吉西他滨1.0g/m2,分别于第1天和第8天静滴,卡培他滨1000mg/m2,2次/日,第1天至第14天,21天为一周期,所有病例均接受至少2个周期的化疗。结果:23例患者入组,均可行疗效及毒性评价,其中完全缓解2例,部分缓解8例,总有效率43.5%。主要毒副反应为骨髓毒性及手足综合症,均较轻。结论:吉西他滨联合卡培他滨方案治疗铂类方案失败的晚期鼻咽癌有较好的疗效,毒副反应小,值得临床进一步研究。     

吉西他滨联合铂类治疗64例晚期非小细胞肺癌临床疗效研究

目的:比较吉西他滨(gemcitabine)联合顺铂(cisplatin)、卡铂(carboplatin)和奥沙利铂(oxaliplatin)三种化疗方案对晚期非小细胞肺癌(NSCLC)的疗效和毒性反应。方法:经病理和细胞学证实的64例晚期NSCLC患者随机分为吉西他滨 顺铂(gemcitabine cisplatin,Gcis)、吉西他滨 卡铂(gemcitabine carbopl-atin,Gcarb)和吉西他滨 奥沙利铂(gemcitabine oxaliplatin,GLOHP)三组。三组均选用吉西他滨1000mg/m2静脉滴注第1、8天。GCis组:顺铂70mg/m2静脉滴注,第1天;GCarb组:卡铂AUC4～6(初治6,复治4～5),静脉滴注,第1天;GLOHP组:奥沙利铂LOHP130mg/m2静脉滴注,第1天。三组均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:Gcis、Gcarb、GLOHP三种方案治疗晚期非小细胞肺癌的有效率分别为52.38%(11/21)、50.00%(10/20)和60.87%(14/23)(P>0.05)。三种方案毒副反应主要为可耐受的骨髓抑制、消化道反应、脱发和外周神经毒性等。结论:吉西他滨联合三种不同铂类的化疗方案均为治疗晚期非小细胞肺癌较为安全有效的化疗方案。     

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。     

吉西他滨联合顺铂治疗晚期食管癌的临床观察

目的 观察吉西他滨联合顺铂一线治疗晚期食管癌的临床疗效及毒副反应.方法 33例无法手术治疗的局部晚期食管癌患者接受吉西他滨联合顺铂方案:吉西他滨1 000 mg·m-2,d1.8,静脉滴注;顺铂30 mg ·m-2,d2～4,静脉滴注,21 d为1周期,所有患者均接受不少于2周期的化疗.治疗结束后评价疗效和毒副反应.结果　33均可评价疗效,其中CR 1例,PR 16例,SD 10例,PD 6例,总有效率为51.5％,临床获益率为81.8％,毒副反应主要是骨髓抑制和消化道反应,治疗有效的患者进食困难和胸痛均不同程度缓解.结论 吉西他滨联合顺铂一线治疗晚期食管癌可获得较好的疗效,且毒副反应可耐受.     

吉西他滨联合顺铂治疗转移性鼻咽癌的临床观察

目的 观察吉西他滨联合顺铂治疗转移性鼻咽癌的临床疗效和毒副反应.方法 30例转移性鼻咽癌均接受化疗.化疗方案:吉西他滨1000 mg/m2,静脉滴注,d1,8;顺铂20 mg/m2,静脉滴注,d1～8.21 d为1个周期,所有病例均接受至少2个周期的化疗.结果 30例转移性鼻咽癌中,完全缓解5例,部分缓解20例,总有效率为83.3%(25/30).中位随访时间16个月(6～24个月),中位疾病进展时间为8.8个月(3.5～18个月),1年生存率为86.7%.主要毒副反应为骨髓抑制和胃肠道反应.结论 吉西他滨联合顺铂方案治疗转移性鼻咽癌疗效较好,毒剐反应可耐受.     

国产吉西他滨联合卡铂治疗晚期非小细胞肺癌的临床观察

背景与目的 化疗在晚期非小细胞肺癌的治疗中具有极为重要的作用。本研究的目的是观察国产吉西他滨（泽菲）联合卡铂治疗晚期非小细胞肺癌的近期疗效、临床受益和毒副反应。方法 对34例初治的晚期（ⅢB及Ⅳ期）非小细胞肺癌患者给予国产吉西他滨联合卡铂治疗。卡铂AUC5，第1天；吉西他滨1000mg／m^2，第1、8天，静脉滴注。21天为一个周期，每例患者治疗3～4周期。结果 34例患者临床有效率（完全缓解＋部分缓解）为44％（15／34），总的临床受益反应率为53％（18／34）。主要毒副反应为血液学毒性，Ⅲ～Ⅳ度白细胞和血小板下降发生率分别为47％和24％，其余毒副反应较轻，可耐受。结论 国产吉西他滨联合卡铂治疗初治的晚期非小细胞肺癌有较好的疗效，毒性反应可以耐受。     

国产吉西他滨联合顺铂方案治疗晚期非小细胞肺癌

 目的 观察国产吉西他滨联合顺铂治疗晚期非小细胞肺癌（NSCLC）的疗效及毒副反应。方法 20例晚期NSCLC患者给予吉西他滨与顺铂联合治疗，吉西他滨1.0 g／m2第1、8天静脉滴注，顺铂30 mg／m2第1 ~ 3天静脉滴注，21~28 d为1个周期，治疗2周期以上。结果 全组无完全缓解（CR）病例，部分缓解（PR）9例，稳定（SD）6例，进展（PD）5例，总有效率45 %，全组中位生存期为11.8个月，1年生存率为45 %，Karnofsky评分增加者占70 %。最常见的毒副反应是骨髓抑制，白细胞减少和消化道反应恶心、呕吐分别占55 %和70 %，其余毒副反应轻微，可耐受。结论 吉西他滨联合顺铂一线治疗晚期NSCLC有较好的疗效，毒副反应可以耐受。     

吉西他滨联合卡铂治疗晚期非小细胞肺癌

目的　观察吉西他滨联合卡铂治疗晚期非小细胞肺癌的疗效及毒副反应。方法　 41例晚期非小细胞肺癌患者给予吉西他滨与卡铂联合治疗 ,吉西他滨 10 0 0mg/m2 ,静脉滴注第 1、8、15天 ,卡铂AUC 5 ,静脉滴注第 1天 ,2 8天为一周期 ,每例患者治疗 2周期以上。结果　全组完全缓解 2例 ,部分缓解 18例 ,稳定15例 ,进展 6例 ,总有效率为 48.8%。初治组有效率为 5 5 .6% ,复治组为 43 .5 % (P >0 .0 5 )。全组中位生存期 11.8月 ,1年生存率为 49%。KPS评分增加者占 70 .7% ( 2 9/4 1)。最常见的毒副反应为骨髓抑制 ,Ⅲ～Ⅳ度白细胞和血小板下降发生率分别为 3 4.1%和 2 9.3 % ,其余毒副反应均轻微 ,可耐受。结论　吉西他滨联合卡铂一线治疗或二线治疗晚期非小细胞肺癌均有较好的疗效 ,毒性可以耐受。     

吉西他滨联合顺铂治疗晚期年轻乳腺癌的临床疗效

目的:观察吉西他滨联合顺铂用于治疗蒽环类和紫杉类耐药的晚期年轻乳腺癌患者的有效性与安全性。方法:收集2008年6月至2011年12月我科收治的25例年轻乳腺癌患者,在辅助、一线或二线治疗中曾应用蒽环类和紫杉类药物,出现进展后选用吉西他滨联合顺铂方案化疗。吉西他滨1000mg/m2静脉滴注,第1、8天;顺铂75mg/m2静脉滴注,分3天,每三周重复。每周期评价毒副反应,化疗3个周期后评价疗效。结果:有效率32.0%,其中CR 0例,PR 8例(32.0%),SD 9例(36.0%),PD 8例(32.0%);中位PFS为7.6个月;主要毒副反应为骨髓抑制及胃肠道反应。结论:吉西他滨联合顺铂方案用于治疗晚期年轻乳腺癌疗效确切,耐受性好。     

国产吉西他滨加顺铂治疗晚期非小细胞肺癌的临床研究

 目的 评价国产吉西他滨（泽菲）加顺铂治疗晚期非小细胞肺癌（NSCLC）的疗效和毒副反应。方法 泽菲1 000 mg／m2，第1，8天静脉滴注，顺铂25 mg／m2，第1 ~ 3天静脉滴注，3周重复。结果 全组25例，共完成76个周期，平均3个周期（2 ~ 6个周期），完全缓解1例，部分缓解9例，客观有效率44 %（11／25），主要毒副反应为骨髓抑制、消化道反应、静脉炎。结论 国产吉西他滨加顺铂的两联化疗在晚期非小细胞肺癌中有较好疗效，毒性可以耐受。     

培美曲塞联合卡铂在鼻咽癌二线治疗中的临床研究

目的观察培美曲塞联合卡铂在鼻咽癌二线治疗中的临床疗效和不良反应。方法培美曲塞500 mg/m2,第1天;卡铂,AUC5,第1天,21 d为1个周期。所有病例均接受至少2个周期的化疗。结果 14例患者入组,均可评价疗效,CR 1例,PR 3例,RR为28.6%(4/14),SD为35.7%(5/14),PD为35.7%(5/14)。中位随访时间6个月,中位TTP 3.5个月,1年生存率为35.7%。主要不良反应为骨髓毒性、疲乏,3例(21.4%,3/14)发生了Ⅲ~Ⅳ度白细胞减少;2例(14.3%,2/14)发生了Ⅲ度血小板减少;2例(14.3%,2/14)发生了Ⅲ度疲乏。结论培美曲塞联合卡铂方案二线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。     

Phase I trial of fixed dose-rate gemcitabine in combination with carboplatin in chemonaive advanced non-small-cell lung cancer: a Cancer Therapeutics Research Group study

PURPOSE: To determine the maximally tolerated dose (MTD) of gemcitabine administered at a fixed dose-rate of 10 mg/m(2) per min in combination with fixed dose carboplatin, to evaluate the toxicity of this regimen and to determine the pharmacokinetics of plasma gemcitabine. METHODS: Patients with advanced stage non-small-cell lung cancer (NSCLC) received carboplatin (AUC 5) on day 1 followed by gemcitabine at a fixed dose rate of 10 mg/m(2) per min in escalating durations of infusion on days 1 and 8 every 21 days. Pharmacokinetic sampling was obtained on day 1, cycle 1 of treatment. RESULTS: A total of 15 patients received carboplatin and gemcitabine in cohorts of three to six patients at three dose levels. The doses of gemcitabine studied were 600, 750, and 900 mg/m(2). The MTD was reached at 900 mg/m(2). Dose-limiting toxicities were thrombocytopenia and liver failure, and with repeated dosing neutropenia was commonly observed. The recommended phase II dose of gemcitabine was 750 mg/m(2). Partial responses were observed at 600 and 750 mg/m(2) of gemcitabine. Plasma gemcitabine did not reach steady state except in one patient with the durations of infusion studied. Plasma concentrations, however, were above 10 micro mol/l between 20 and 90 min in all patients. CONCLUSIONS: Gemcitabine administered as a 75-min infusion at a fixed dose rate of 10 mg/m(2)/min on days 1 and 8 in combination with carboplatin on day 1 every 21 days is tolerable and active in NSCLC. Pharmacokinetic studies demonstrated that the target plasma gemcitabine concentration above 10 micro mol/l was achieved. Further studies are warranted to compare this regimen against standard regimens of carboplatin and gemcitabine.     

Phase II study of an alternate carboplatin and gemcitabine dosing schedule in advanced non-small-cell lung cancer

We conducted a phase II single-institution trial in a homogenous patient population with advanced non-small-cell lung cancer to determine whether changing the carboplatin schedule in the carboplatin/gemcitabine doublet would enhance tolerability and/or results. Thirty patients with stage IIIB (with malignant effusion) or stage IV disease received gemcitabine 1100 mg/m2, days 1 and 8 plus carboplatin at an area under the curve of 5 on day 8. Cycles were repeated every 28 days, up to 6 cycles. A response rate of 10% was demonstrated (none complete), but an additional 45% of patients had stable disease. The median time to progression was 5.8 months and the median survival was 8.3 months. A 1-year survival rate of 27% and a 2-year survival rate of 16% were seen. The main nonhematologic toxicity was non-neutropenic infection. Thrombocytopenia occurred in 8 patients (27%; 7 grade 3, 1 grade 4). Carboplatin/gemcitabine with a day 8 administration of carboplatin is well tolerated with a similar survival to established platinum-based doublets.     

健择联合卡铂治疗晚期肺癌

目的研究健择联合卡铂治疗晚期肺癌的疗效及毒性反应.方法经病理组织学或细胞学证实的58例的晚期肺癌患者给予健择1000 mg/m2静脉滴注,第1、8天;卡铂第1天以AUC=5计算所得的剂量,静脉滴注,21天为1周期.结果可评价疗效58例,CR 1例,PR29例,SD 21例,PD 7例,RR为51.7%.毒副作用主要为白细胞及血小板减少,但均可耐受,胃肠道反应及肾毒性轻.结论健择联合卡铂治疗晚期肺癌疗效确切,毒副作用可以耐受.     

Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group.

PURPOSE: This phase III study compared overall survival in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) when treated with single-agent gemcitabine versus gemcitabine/carboplatin. Secondary objectives were to compare response, time to progression, toxicity, and quality of life. PATIENTS AND METHODS: Chemotherapy-naive patients received either gemcitabine alone (1,250 mg/m2 on days 1 and 8; gemcitabine arm) or with carboplatin (area under the curve 5 on day 1; GC arm) every 21 days. RESULTS: Demographics and disease characteristics of 334 randomly assigned patients were comparable on both arms. An intent-to-treat analysis showed significantly better overall survival (log-rank P = .0205) and 2-year survival (15% v 5%; P = .009) favoring the GC arm. Per Cox multivariate analysis, only two covariates, treatment arm (GC v G) and baseline performance status (0 or 1 v 2), independently influenced survival. Per-protocol analyses showed significantly longer median time to progression (5.7 v 3.9 months; P = .0001) and significantly higher objective response rate (29.6 v 11.3%; P < .0001) in the GC arm. Grade 3 to 4 leucopenia and thrombocytopenia were significantly more pronounced in the GC arm (P for both variables < .001) but importantly without associated increases in fever, infection, bleeding, or hospitalizations. There was no discernible difference in global quality-of-life patterns between treatment arms. CONCLUSION: In advanced NSCLC, gemcitabine/carboplatin therapy resulted in significant survival benefit compared with single-agent gemcitabine without undue increase in toxicity.     

Paclitaxel, carboplatin, and gemcitabine in metastatic nasopharyngeal carcinoma: a Phase II trial using a triplet combination

BACKGROUND: Patients with nasopharyngeal carcinoma (NPC) are treated primarily with radiotherapy. In the disseminated state, platinum-based, 2-drug combination regimens yielded response rates of 55-75%, achieving a median survival of 10-12 months. With the proven efficacy of second-generation cytotoxics like paclitaxel and gemcitabine in patients with metastatic NPC, the authors hypothesized that a triplet combination incorporating these newer cytotoxics may improve treatment results. METHODS: Thirty-two patients with metastatic NPC were treated with combination chemotherapy that included paclitaxel 70 mg/m(2) on Days 1 and 8, carboplatin dosed to area under curve of 5 on Day 1, and gemcitabine 1000 mg/m(2) on Days 1 and 8 every 21 days for a maximum of 8 cycles. RESULTS: Two patients achieved a complete response, and 23 patients achieved a partial response, for an overall response rate of 78%. The main toxicities were hematologic, with 41% of patients experiencing Grade 3 or 4 anemia, 41% of patients experiencing Grade 3 or 4 thrombocytopenia, and 78% of patients experiencing Grade 3 or 4 neutropenia. The median time to disease progression was 8.1 months, and the median overall survival was 18.6 months. CONCLUSIONS: The combination of paclitaxel, carboplatin, and gemcitabine showed promising efficacy against metastatic NPC but at the expense of considerable toxicity.     

Phase Ib study of dovitinib in combination with gemcitabine plus cisplatin or gemcitabine plus carboplatin in patients with advanced solid tumors

Purpose

Dovitinib is a small molecule kinase inhibitor with activity against the fibroblast growth factor and vascular endothelial growth factor receptor families. The purpose of this phase Ib study was to define the recommended phase 2 dose of the combinations of gemcitabine and cisplatin or gemcitabine and carboplatin plus dovitinib.

Methods

Patients with advanced solid tumors were enrolled in two parallel dose escalation arms (cisplatin- or carboplatin-based regimens). Treatment was administered with gemcitabine (1,000 mg/m² on days 1 and 8), cisplatin (70 mg/m²), or carboplatin (AUC 5) on day 1, and dovitinib (orally on days 1–5, 8–12, and 15–19), every 21 days. The starting dose of dovitinib was 300 mg and was dose escalated in successive cohorts using 3 + 3 dose escalation rules.

Results

Fourteen patients with advanced solid tumors were enrolled, five to the cisplatin arm and nine to the carboplatin arm. Patients enrolled in the cisplatin arm received a median of two cycles of treatment (range 1–5), and patients enrolled in the carboplatin arm received a median of one cycle of treatment (range 1–4). There were no protocol-defined dose-limiting toxicities in the cisplatin arm. However, the cohort was closed due to the need for frequent dose delays and/or reductions and two patients experiencing severe thromboembolic events. There were two dose-limiting toxicities in the carboplatin arm at the starting dose level of dovitinib (both prolonged neutropenia), and the dose of dovitinib was de-escalated to 200 mg. Two additional dose-limiting toxicities (prolonged neutropenia and febrile neutropenia) occurred in the lower dose cohort, and the study was closed. No patients achieved an objective response to treatment.

Conclusions

Dovitinib in combination with gemcitabine plus cisplatin or gemcitabine plus carboplatin was poorly tolerated due to myelosuppression.     

Gemcitabine and carboplatin in patients with locally advanced or metastatic non-small cell lung cancer: a prospective phase II study

PURPOSE: The primary objective of this phase II study was to determine the tumor remission rates in previously untreated patients with advanced or metastatic non-small cell lung cancer (stage IIIB and IV), after treatment with gemcitabine plus carboplatin. Secondary objectives of this study were to determine toxicity, median survival and progression free survival in the same patient population treated with gemcitabine plus carboplatin. PATIENTS AND METHODS: Chemonaive patients with histological or cytological diagnosis of stage IIIB or IV NSCLC and Karnofsky performance status >/=60 received gemcitabine 1000 mg/m(2) over 30 min on days 1 and 8 and carboplatin AUC 5.0 over 30 min on day 1 after the gemcitabine infusion. Treatment cycles were repeated every 21 days for a maximum of six cycles, or until disease progression or unacceptable toxicity occurred. RESULTS: Of the 60 patients qualified for efficacy analysis, five achieved complete remissions, 15 partial remissions and 33 had stable disease, for an overall objective response rate (CR+PR) of 33.3% (95% CI, 21.7-46.7%). Four patients had progressive disease. The predominant toxicity was hematologic, with grade 3/4 leucopoenia being most common (35% patients). The median duration of response was 5 months, median time to progression was 6 months and median survival was 9 months with 80% of patients censored. CONCLUSION: Gemcitabine plus carboplatin is an effective and well tolerated treatment for advanced NSCLC.     

A phase II trial of gemcitabine/carboplatin with or without trastuzumab in the first-line treatment of patients with metastatic breast cancer

PurposeThe purpose of this study was to evaluate the efficacy and toxicity of the combination of gemcitabine and carboplatin (and with trastuzumab in patients with HER2-positive disease) as first-line treatment for patients with metastatic breast cancer (MBC).Patients and MethodsSeventy-four patients who had received no previous chemotherapy for MBC were enrolled. Patients with HER2-negative breast cancer received treatment with gemcitabine 1000 mg/m² intravenously (I.V.) on days 1 and 8 and carboplatin area under the curve (AUC) 5 I.V. on day 1. Cycles were repeated every 21 days. Patients with HER2-positive disease also received trastuzumab 8-mg/kg I.V. loading dose, then 6 mg/kg I.V. every 21 days. After the first 29 patients were treated, the carboplatin dose was lowered to AUC 4. Patients were re-evaluated every 6 weeks; responses were measured using Response Evaluation Criteria in Solid Tumors criteria.ResultsIn patients with HER2-negative disease, gemcitabine/carboplatin produced a 34% major response rate; an additional 28% of patients had stable disease ≥ 6 months (overall disease control rate, 62%). Gemcitabine/carboplatin/trastuzumab produced an overall response rate of 66%, with a disease control rate of 77%. Grade 3/4 myelosuppression was common, even after reduction of the carboplatin dose. Only 3 patients treated with the lower dose regimen developed neutropenia and fever, but platelet and red blood cell transfusions were necessary in 24% and 40% of patients, respectively. Trastuzumab did not add to hematologic toxicity. Severe nonhematologic toxicity was uncommon.ConclusionGemcitabine/carboplatin and gemcitabine/carboplatin/trastuzumab are active first-line regimens for patients with MBC. The gemcitabine/carboplatin combination causes more grade 3/4 myelosuppression than other standard combination regimens for MBC; however, severe nonhematologic toxicity is minimal.