CE方案治疗肺癌的疗效观察

本组用卡铂350～420mg/m~2 足叶乙甙100mg×5天(即CE方案)治疗肺癌64例,每例均治疗2周期以上,总有效率(CR PR)为40.6％,其中小细胞肺癌25例,有效率80.0％,非小细胞肺癌有效率为15％.毒性反应主要是骨髓抑制,胃肠道及肾毒性较轻.     

Dose-escalation Study of Oral Etoposide and Carboplatin in Patients with Advanced Lung Cancer

A dose-escalation study of daily etoposide and carboplatin wascarried out on 23 patients with advanced lung cancer using astarting dose of 40 mg/m²/day etoposide given orally for 21days and 250 mg/m² carboplatin given intravenously (IV) on day1. A total of 41 courses were given. Myelosuppression was themajor dose-limiting toxicity. The maximum tolerated dose wasreached at the fourth level with 40 mg/m²/day etoposide for21 days and 400 mg/m² carboplatin on day 1, once every 4 weeks.Non-hematological toxicities were generally mild or reversible.The recommended doses of this combination chemotherapy are 40mg/m²/day etoposide for 21 days and 350 mg/m² carboplatin onday 1. The response rate for non-small cell lung cancer andsmall cell lung cancer was 16.7% and 60% (95% confidence intervalsof 3.6% to 41.4%, and 14.7% to 94.7%), respectively. A phaseII study is necessary to define the efficacy and safety of thiscombination chemotherapy.     

Therapeutic Drug Monitoring in 21-Day Oral Etoposide Treatment for Lung Cancer

We aimed to determine whether or not therapeutic drug monitoring is applicable to 21-day oral etoposide treatment for lung cancer. As the starting dose, a 25-mg capsule of etoposide was taken orally three times daily (75 mg/body). To achieve the target concentration range of 1.0 to 1.5 μg/ml, the dose was changed to two (50 mg/body) or four (100 mg/body) times a day from day 5, depending on the mean concentration obtained on days 3 and 4 (C_before). The mean concentration was calculated by use of a limited sampling model we constructed previously. Among 26 courses in 15 patients, two patients experienced grade 4 leukopenia plus neutropenia, and one of them died on day 20. Because nausea/emesis prevented the planned dose escalation in one patient, we excluded two courses of this patient from the pharmacokinetic analysis of dose modification. Among 5 courses with dose reduction, the C_before of 1.7±0.1 (μg/ml, mean±SE) was decreased to 1.3±0.2 after day 5 (C_after). Among 7 courses with dose escalation, the C_before of 0.9±0.0 was increased to the C_after of 1.2±0.1. Among the remaining 12 courses without dose modification, the C_before and the C_after were 1.2±0.0 and 1.3±0.1, respectively. Hematologic toxicities tended to correlate with the drug concentration. TDM is thus applicable to oral etoposide given according to this schedule, and a larger study is now needed to confirm that the therapeutic efficacy is improved by introducing TDM.     

低剂量长疗程口服足叶乙甙对肺癌的治疗作用

本组对足叶乙甙（ＶＰ－１６）口服胶囊治疗肺癌进行临床观察。４８例可评价病人随机分为两组。治疗方案：卡铂＋ＶＰ－１６，卡铂３００ｍｇ／ｍ２，ｄ１，两组用法相同，ＶＰ－１６观察组口服７５ｍｇ，ｄ１～１４或５０ｍｇ，ｄ１～２１，对照组１００ｍｇ静脉点滴ｄ１～５。观察组共２３例病人，治疗有效率为６９．５６％（ＳＣＬＣ：８４．６２％，ＮＳＣＬＣ：５０．００％），对照组２５例，有效率为５２．００％（ＳＣＬＣ：６６．６７％，ＮＳＣＬＣ：３０．００％），观察组高于对照组，但无统计学意义，可能与病例少有关。ＶＰ－１６低剂量长疗程口服治疗肺癌有较好的疗效，毒副反应轻微，应用方便，是一种值得推广的肿瘤化疗的新方法     

顺铂或卡铂加足叶乙甙治疗晚期肺癌105例临床分析

我所自1992年1月至1995年8月，用顺铂或卡钻加足叶乙甙治疗晚期肺癌105例，其中小细胞肺癌49例，非小细胞肺癌56例。顺铂组有效率小细胞肺癌为72．0％，非小细胞肺癌为38．5％；卡钥组有效率小细胞肺癌为79．2％，非小细胞肺癌为26．7％。两方案的主要毒性为胃肠道毒性和骨髓抑制，胃肠道毒性顺钥组较卡铂组为重，而骨髓抑制以卡铂组为明显。本文结果提示顺铂或卡铂加足叶乙甙治疗小细胞肺癌的有效率高，可作为治疗小细胞肺癌的首选方案。治疗非小细胞肺癌的有效率顺铂组稍高于卡铂组，但两组疗效均欠理想，为寻找治疗非小细胞肺癌更为有效的化疗方案，仍有待临床进一步探讨。     

Phase II Study of Roniciclib in Combination with Cisplatin/Etoposide or Carboplatin/Etoposide as First-Line Therapy in Patients with Extensive-Disease Small Cell Lung Cancer

Introduction

This phase II study evaluated the efficacy and safety of the pan-cyclin–dependent kinase inhibitor roniciclib with platinum-based chemotherapy in patients with extensive-disease SCLC.

长期口服VP-16联合顺铂治疗肺癌38例疗效分析

长期低剂量口服ＶＰ－１６（５０ｍｇ／ｍ２／ｄ×２１天）联合静滴ＤＤＰ（２０ｍｇ／ｍ２／ｄ×５天）治疗肺癌病人３８例，其中ＳＣＬＣ２４例，ＣＲ４例，ＰＲ１６例，有效率８３．３％；ＮＳＣＬＣ１４例，ＰＲ５例，有效率３５．７％。平均缓解时间ＳＣＬＣ６个月，ＮＳＣＬＣ６．５个月。毒副作用主要表现为骨髓抑制、脱发和胃肠道反应，其它毒性少见。     

Phase II Study of Carboplatin in Small Cell Lung Cancer

Carboplatin (CBDCA; cis-diammine-1, 1-cyclobutane dicarboxylateplatinum II), a new platinum analogue, was administered to 18patients with small cell lung cancer (SCLC) at a dose of 300–450mg/m² intravenously every four weeks, in a phase II study. Allpatients could be evaluated to assess response and 17 for toxicity.The overall response rate was 28% (5/18), including one completeresponse. Of eight patients previously untreated, four (50%)showed a response, including one complete response. The responserate in patients with no previous cisplatintreatment was 50%(5/10). Response durations in five responders were 2, 3, >4,> 10 and 11 months. Toxicity was primarily hematologic,with thrombocytopenia being dose-limiting. Thrombocytopenia(<75,000/mm³) was observed in 12 patients (71%), six requiringplatelet transfusion. Leukopenia (<3,000/mm³) was observedin 11 patients (65%). There were no episodes of serious infectionor bleeding, however. Myelosuppression was more severe in heavilypretreated patients than in patients previously untreated. Dosereductions were required following multiple treatments for cumulativemyelotoxicity. Mild to moderate nausea and vomiting occurredin seven patients (44%). Nephrotoxicity and ototoxicity werenot observed. Carboplatin was demonstrated to be an active agentagainst SCLC. Further investigation into dose and schedule ofCBDCA in combination chemotherapy is warranted.     

Phase II Study of Carboplatin in Non-small Cell Lung Cancer

Forty four patients with advanced non-small cell lung cancer(NSCLC) were treated with carboplatin (CBDCA; cis-diammine-1,1-cyclobutane dicarboxylate platinum II) at a dose of 400–450mg/m² intravenously every four weeks in a phase II study. Fortythree patients were evaluated for response and toxicity. Twopatients achieved responses resulting in an overall responserate of 4.7% (95% confidence limits: 0.6–15.8%); one ofthese had not been treated previously and the other had beentreated previously with vinblastine. The durations of theirresponses were 5 and 7 months, respectively. The response ratein 28 previously untreated patients was 3.6% (1/28; 95% confidencelimits: 0.1–18.3%). Myelosuppression was the most commonlyfound toxicity, and thrombocytopenia especially was dose-limiting.Thrombocytopenia (<75,000/mm³) was observed in 12 patients(28%). Leukopenia (<3,000/mm³) was observed in 14 patients(33%). No serious infection or bleeding occurred, however. Treatmentwith 400–450 mg CBDCA/m² was well tolerated in the goodrisk patients in this study. Mild to moderate emesis was observedin 28 patients (65%). No renal toxicity, neurotoxicity or ototoxicitywas seen. It was demonstrated that CBDCA had little efficacyin NSCLC at the dose and schedule given in the present study.     

A Phase II Study of Carboplatin and Prolonged Administration of Oral Etoposide in Patients with Small-Cell Lung Cancer

Prolonged oral administration of etoposide may have a theoretical advantage over intravenous infusion, and carboplatin has a more favorable toxicity profile than cisplatin. A combination of carboplatin 300 mg/m² and oral etoposide 40 mg/m²/day for 21 days was assessed in 74 (42 limited, 32 extensive disease) previously untreated patients with small-cell lung cancer. Response rate was 69% (CR 19%, PR 50%) for limited disease and 72% (CR 9%. PR 63%) for extensive disease. Median response duration and overall survival was 6.6 and 10.1 months for limited disease, and 5.3 and 9.1 months for extensive disease, respectively. One-year and two-year survival was 36 and 10% for limited disease and 31 and 2% for extensive disease, respectively. The major toxicity was hematological with grade 4 or greater neutropenia in 36% and grade 4 thrombocytopenia in 16% and one patient died of neutropenic fever. Non-hematologic toxicities were mild and grade 3 emesis was observed in 5% of patients. Carboplatin combined with 21-day oral etoposide showed only modest activity against small-cell lung cancer with high toxicity and did not merit further evaluation.     

吉西他滨联合卡铂治疗非小细胞肺癌疗效观察

目的观察吉西他滨联合卡铂治疗非小细胞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48例非小细胞肺癌患者给予吉西他滨1000mg/m2静滴,第1,8天,卡铂AUC5静滴,第1天,3周为1周期。结果可评价疗效48例,有效率为52%,毒副反应主要为白细胞及血小板降低,但均可耐受。结论吉西他滨联合卡铂治疗非小细胞肺癌具有较好的疗效,且毒性反应可以耐受。     

拉司太特联合化疗治疗晚期恶性肿瘤27例

目的评价拉司太特在联合化疗中的疗效,并观察在临床应用中的毒副作用。方法用拉司太特50mg／m2d1-14口服为主,组成CHEP、CE和ED方案,治疗晚期恶性肿瘤27例。结果总有效率为62.96％,对非何杰金氏淋巴瘤为62.50％,小细胞肺癌为70.00％,非小细胞肺癌为50.00％及1例胆囊癌有效。剂量限制性毒性为骨髓抑制.其中CHEP方案相对较重。CE和ED方案WBC最低值在给药后20天左右,Pt在17-18天左右。结论拉司太特联合化疗治疗晚期NHL、SCLC、NSCLC取得良好疗效,毒副反应可以耐受。     

紫杉醇联合铂类药物治疗晚期非小细胞肺癌的临床研究

目的评价紫杉醇联合铂类药物对晚期非小细胞肺癌的客观疗效及毒副作用。方法经病理组织学证实的晚期非小细胞肺癌59例,采用紫杉醇135mg/m^2,静脉滴注,第1天,顺铂80mg/m^2,分3天给药,第2～4天,或卡铂350mg/m^2,静脉滴注,第2天,2l天为1个周期,2个周期以上评价疗效及毒副作用。结果全组PR24例,SD23例,PD12例,总有效率为40.7%。主要毒副作用为恶心、呕吐、骨髓抑制、关节肌肉痛等。大部分为Ⅰ～Ⅱ度不良反应,患者耐受良好。结论紫杉醇联合铂类方案是1种对晚期非小细胞肺癌有效的治疗方案,毒副作用轻,值得临床进一步研究应用。     

健择联合卡铂治疗70岁以上进展期非小细胞肺癌患者的观察

目的观察健择联合卡铂方案治疗70岁以上老年进展期非小细胞肺癌(NSCLC)患者的疗效及副反应,评价该方案的可行性。方法对采用健择联合卡铂化疗的44例进展期NSCLC患者(初治)进行回顾性分析,其中70岁以下24例,70岁以上20例。化疗方案:<70岁健择1200mg/m2,d1,8;卡铂AUC=5,d1;≥70岁健择1000mg/m2,d1,8;卡铂AUC=4,d1。每3周重复,至少治疗2周期,2周后评价疗效。结果70岁以下组共完成89周期化疗,平均3.7周期,有效率(CR+PR)45.8%,70岁以上组共完成66周期,平均3.3周期,有效率(CR+PR)40.0%,两组近期有效率比较差异无统计学意义(P>0.05)。两组在Ⅲ~Ⅳ骨髓抑制、严重恶心呕吐、脱发、肝肾功能损害方面差异无统计学意义(P>0.05),70岁以下组严重便秘1例,70岁以上组5例,差异有统计学意义(P<0.05)。两组中分别有2例患者化疗后血小板明显升高,1例56岁男性患者发生双下肢深静脉血栓,抗凝治疗后好转。结论健择联合卡铂化疗治疗70岁以上进展期NSCLC,疗效较好,毒副反应可耐受。     

吉西他滨联合卡铂治疗晚期非小细胞肺癌

目的研究吉西他滨（Gem）联合卡铂（CBP）方案治疗晚期非小细胞肺癌（NSCLC）的疗效和毒副作用。方法经病理学确诊的非小细胞肺癌38例。其中腺癌24例,鳞癌11例,肺泡细胞癌2例,大细胞癌1例。初治34例,复治4例;11期12例（Ⅲa期2例,Ⅲb期10例）,Ⅳ期26例。采用吉西他滨1000mg／m^2,第1、8天静滴;卡铂AUC=6,21天为1个周期。结果完全缓解（CR）1例,部分缓解（PR）16例,稳定（SO）11例,进展（PD）10例,总有效率为44．7％。中位进展期6个月,中位生存期14个月,1年生存率53．6％。Ⅲ-Ⅳ度血小板下降36．8％,为主要血液性毒性。结论吉西他滨联合卡铂方案治疗晚期NSCLC疗效确切,肾毒性及胃肠道等毒性反应较少。血液性毒性可以耐受,患者对治疗有较好的依存性,对老年患者尤为适宜,且方便门诊应用。     

Pharmacokinetic Study of Carboplatin Given on a 5-Day Intravenous Schedule

We investigated whether carboplatin pharmacokinetics is altered when the drug is delivered daily over 5 days, compared to a single-day infusion. Carboplatin was infused in 11 patients with lung cancer, who were randomly assigned to 2 groups. In the first group, the agent was administered on a conventional single-day schedule in the first course and then on a 5-day schedule in the second course. In the second group, the order was reversed (crossover design). The dose was calculated using Calvert's formula with 24 h creatinine clearance (Ccr, ml/min) as a substitute for glomerular filtration rate (GFR): carboplatin (mg) = AUC X (Ccr+25), where AUC denotes the area under the concentration versus time curve (mg ml^–1 min). No difference of carboplatin clearance between the single-day and 5-day schedule was observed (94.8± 19.9 versus 96.1+29.9 ml/min, P =0.818, paired t test). The formula systematically overestimated the carboplatin clearance; the ratio of estimated clearance/ observed clearance ranged from 1.01 to 1.58 (median 1.28; 95% confidence interval, 1.18 to 1.39). We concluded that the individual dosing strategy based on renal function can be applied with a 5-day schedule as well as a single-day schedule. Carboplatin is overdosed when Ccr is substituted for GFR in Calvert's formula.