Epirubicin or epirubicin and vindesine in advanced breast cancer. A phase III study

One hundred thirty-three evaluable patients with advanced breast cancer entered a randomized trial comparing epirubicin 60 mg/m2 with a combination of epirubicin 45 mg/m2 and vindesine 3 mg/m2 day 1 and 8 every 4 weeks. In all 10 premenopausal women an oophorectomy was performed. Seventy-five patients had previously received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) for advanced disease and 68 had received adjuvant chemotherapy (cyclophosphamide or CMF). Among evaluable patients (72 in the epirubicin group and 61 in the epirubicin + vindesine group) response rates were as follows: complete response--seven versus six; partial response--31 versus 22; no change--16 versus 17 (p greater than 0.40). Median time to disease progression was 6 months in both groups and median survival times were identical (12 months). Thrombocytopenia was less frequent in the epirubicin + vindesine group (p less than 0.01). In the epirubicin + vindesine group, mild to moderate peripheral neuropathy was observed in 40% of the patients. Congestive heart failure developed in one patient with a cumulative dose of epirubicin less than 1000 mg/m2 and in 7 of 15 patients who had greater than 1000 mg/m2. Four died of this cause. In conclusion, epirubicin is effective as a single agent for advanced breast cancer. The combination with vindesine does not increase its efficacy.     

同步放化疗治疗局部晚期非小细胞肺癌62例

目的探讨同步放化疗治疗局部晚期非小细胞肺癌的近期疗效和急性毒副反应。方法62例Ⅲ期非小细胞肺癌患者放疗前1周开始化疗,多西他赛40mg／m^2,第1、8天给药;顺铂20mg／m^2,第1～4天给药,每21天重复,共2～3个周期;常规放疗200 CGy／次／d,5d／周,DT 6000—7000 CGy。结果完全缓解率为29．0％,部分缓解率为58．1％,总有效率87．1％。主要毒副反应为急性放射性食管炎（56．5％）、放射性肺炎（41．9％）、骨髓抑制（35．5％）和胃肠道反应（16．1％）,大多数患者经过对症治疗均能耐受。结论多西他赛联合顺铂配合放疗同步治疗局部晚期非小细胞肺癌,近期疗效肯定,远期疗效和并发症有待进一步观察。     

VINDESINE WITH CYCLOPHOSPHAMIDE-EPIRUIBIN-CISPLATININ THE TREATMENT LOCALLY ADVANCED NON-SMALCELL LUNG CANCER

Lungcancerrepresentstheleadingcauseofcancerdeathsinhuman.Non-smallcelllungcancer(NSCLC)accountsforabout75%--85%ofalllungcancersandcanbesurgicallyresectedinonly30%--40%ofpatientswithlimiteddisease.[1'21Theremainingpatients,withlocallyadvancedormetasta...     

A prospective study on glioblastoma in the elderly

BACKGROUND: Elderly patients (age > 65 years) with glioblastoma multiforme frequently are excluded from clinical studies, and prospective trials for patients with this age group do not exist to date. METHODS: The authors conducted a prospective trial in 79 consecutive elderly patients with glioblastoma who underwent surgery and received radiotherapy (59.44 grays in 33 fractions; Group A; n = 24 patients) or received the same radiotherapy plus adjuvant chemotherapy with procarbizine, lomustine, and vincristine (PCV; lomustine 110 mg/m(2) on Day 1, procarbazine 60 mg/m(2) on Days 8-21, and vincristine 1.4 mg/m(2) on Days 8 and 29 every 42 days; Group B; n = 32 patients), or received the same radiotherapy plus adjuvant temozolomide (150 mg/m(2) for 5 days every 28 days; Group C; n = 22 patients). RESULTS: The median time to disease progression (TTP) and median survival MST were 7.2 months (95% confidence interval [95%CI], 6.34-8.64) and 12.5 months (95%CI, 11.6-14.8), respectively. The TTP was significantly better for Group C compared with Groups A and B (10.7 months vs. 5.3 months and 6.9 months, respectively; P = 0.0002). Karnofsky performance status (KPS) (P < 0.001) and temozolomide (P < 0.001) were the only independent prognostic factors. Overall survival was better in Group C compared with Group A (14.9 months vs. 11.2 months; P = 0.002), but there were no statistical differences found between Groups A and B or between Groups B and C. Only KPS (P < 0.001) was predictive of overall survival, even if temozolomide chemotherapy was very close to the significance level (P = 0.058). Hematologic Grade 3-4 toxicity was higher with the PCV chemotherapy regimen compared with the temozolomide chemotherapy regimen. CONCLUSIONS: Age alone should not preclude appropriate treatment in elderly patients with good performance status, for whom definitive radiation therapy and adjuvant chemotherapy with temozolomide is advised.     

同期放化疗治疗肺癌所致上腔静脉综合征临床研究

目的应用同期放化疗治疗肺癌所致上腔静脉综合征,以期提高疗效及安全性。方法对符合入组病例,经一般处理后,予诱导化疗2周期,小细胞肺癌(SCLC)应用EP方案:DDP 20 mg/ m~2,静脉滴注,d1～4;Vp-16 100 mg/m~2,静脉滴注,d 5～7。非小细胞肺癌(NSCLC)应用GP方案:GEM 1000 mg/m~2,静脉滴注,d1、8;DDP 20 mg/m~2,静脉滴注,d2～4。同期放化疗:诱导化疗结束1～2周后无放疗禁忌证,可予以同期放化疗:DDP 20 mg/m~2,静滴,d1～4,3周后重复,共2周期。同时予以肺部病灶加纵隔及双锁上根治性放疗,每次300～400 cGy,每日应用地塞米松5 mg,2～4次后再改为200 cGy/d。照射剂量应视肿瘤的病理类型而定。小细胞肺癌(SCLC)3000～3500 cGy/3～4周,非小细胞肺癌(NSCLC)及未分型5000～6000 cGy/5～6周,其间注意放化疗毒副应及并发症的处理。补充化疗:同期放化结束后,休息3～4周,应进行补充化疗。据不同病理类型采用不同的化疗方案及疗程。小细胞肺癌予以CAO、EP、CE等方案化疗4～6周期,非小细胞肺癌予以NP、GP、TP等方案化疗2～3周期,未分型采用EP方案化疗3～4周期。结果入组53例,51例可评价疗效,临床症状缓解率为89.6%。CR 6例,PR 33例,NC 9例,PD 5例,有效率为73.6%。1年生存率56.3%,2年生存率33.9%,3年生存率9.4%。结论此种治疗模式可作为肺癌合并SVCS的规范治疗模式,亦可对其他恶性肿瘤合并SVCS的治疗有较好的指导作用。     

对症治疗与联合化疗治疗晚期非小细胞肺癌

目的 评价联合化疗对晚期非小细胞肺癌（ＮＳＣＬＣ）患者生存期的影响。方法 ７０例晚期非小细胞肺癌患者配对分组;３５例拒绝化疗者,接受对症治疗（对症组）。３５例接受联合化疗,丝裂霉素８￣１０ｍｇ／ｍ＾２,第１天,顺铂２０ｍｇ／ｍ＾２,第１￣５天,长春酰胺３ｍｇ／ｍ＾２,第１,８天,每４周重复,２￣４周期后,口服喃呋啶２００￣３００ｍｇ,每天３次,至肿瘤复发或进展止。结果 中位生存期化疗组为９个月,对     

Survival outcome of inoperable non-small cell lung cancer patients receiving conventional dose epirubicin and Paclitaxel as first-line treatment

OBJECTIVE: High-dose epirubicin was shown to be effective in the treatment of inoperable non-small cell lung cancer (NSCLC). Paclitaxel is synergistic to a conventional dose of anthracyclines in the treatment of advanced cancer. A phase II study was designed to test the effectiveness of combining paclitaxel with a conventional dose of epirubicin in inoperable NSCLC patients. METHODS: Eligibility criteria included inoperable stage IIIB or IV NSCLC patients, Eastern Cooperative Oncology Group performance status of 0-2, measurable or evaluable disease and adequate organ function. Epirubicin 70 mg/m2 intravenous infusion for 15 min was given on day 1. Paclitaxel 175 mg/m2 intravenous infusion for 3 h was given on day 2. Cycles were repeated every 21 days. Tumor response was evaluated every two cycles. Patients received treatment until disease progression, unacceptable toxicity or stable disease after cycle 6. RESULTS: Thirty-eight patients received a total of 185 cycles (median 6 cycles). Seventeen patients responded to treatment (response rate 44.7%). Twenty-six (68%) patients received second-line chemotherapy. All patients were followed until their death. Median survival was 11.9 months (95% confidence interval 9.0-14.9 months). Median time-to-treatment-failure was 4.6 months. CONCLUSION: Conventional dose epirubicin plus paclitaxel is effective as a first-line treatment for inoperable NSCLC patients.     

NP和MVP方案治疗非小细胞肺癌的初步比较

目的]初步比较NP和MVP方案对晚期非小细胞肺癌(NSCLC)的疗效和不良反应。[方法]45例Ⅲ期或Ⅳ期NSCLC患者随机分为A组和B组 ,A组应用NP(去甲长春花碱 顺铂)方案化疗 ,B组应用MVP(丝裂霉素 长春花碱酰胺 顺铂)方案化疗 ,至少连用2周期后评价疗效和不良反应。[结果]两组均无完全缓解病例 ,A组有效率为45 5 %(10/22) ,B组35 0 %(7/20) ,差异无显著性(P>0 05)。其中对腺癌有效率A组为53 3 %(8/15) ,B组为35 7%(4/14)。A组静脉炎发生率为27 3 %(6/22) ,B组为0(P<0 05) ;其它不良反应两组均相似。[结论]NP方案为治疗晚期NSCLC较为有效和安全的化疗方案。     

国产紫杉醇脂质体治疗非小细胞肺癌和乳腺癌的Ⅲ期临床试验报告

目的:比较国产注射用紫杉醇脂质体 顺铂与紫杉醇 顺铂治疗非小细胞肺癌的临床疗效和安全性。比较国产注射用紫杉醇脂质体 表阿霉素和紫杉醇 表阿霉素治疗乳腺癌的临床疗效和安全性。方法:本试验为多中心,开放式,随机,对照研究。分试验组A和对照组B两组。小细胞肺癌:A组注射用紫杉醇脂质体135mg/m2/d1 顺铂75mg/m2/周期,每3周重复;B组注射用紫杉醇135mg/m2/d1 顺铂75mg/m2/周期,每3周重复。乳腺癌:A组注射用紫杉醇脂质体135mg/m2/d1 表阿霉素60mg/m2/d1,每3周重复;B组注射用紫杉醇135mg/m2/d1 表阿霉素60mg/m2/d1,每3周重复。结果:本中心共有21例病人入组,20例病人可评价疗效和不良反应。非小细胞肺癌和乳腺癌各10例。试验组总有效率71.4%(10/14)。对照组总有效率33.3%(2/6),但无显著性差别。主要不良反应为血液学毒性,以白细胞和粒细胞的减少最明显,但统计学上无显著性差异。其它非血液学毒性主要为恶心呕吐,脱发,疲劳和肌肉关节痛,两组无明显差别。结论:国产注射用紫杉醇脂质体是一种安全、有效的药物。     

Vindesine with cyclophosphamide-epirubicin-cisplatin in the treatment locally advanced non-small cell lung cancer

Objective: To evaluate the addition of vindesine to a cyclophosphamide-epirubicin-cisplatin (CAP) regimen for treating the patients with locally advanced non-small cell lung cancer (NSCLC). Methods: From May 1994to August 1998, 59 previously untreated patients with stage Ⅲa and Ⅲb non-small cell lung cancer were enrolled into this trial. Patients characteristics were the following: the median age was 52 years; the median performance status was 1; there were 19 stage Ⅲa and 40 stage Ⅲb; there were 47 adenocarcinoma, 10squamous cell carcinoma and 2 large cell carcinoma. All patients were treated with vindesine (2 mg/m2, on day 1and day 8), cyclophosphamide (0.6/m2, on day 1),epirubicin (40 mg/m2, on day 1) and cisplatin (60 mg/m2,on day 1) every 3 or 4 weeks. Results: Four achieved a complete response (6.8%), 29 achieved a partial response (49.2%), 15 had stable disease, and 10 had progressive disease. A clinical improvement was in 45 of 59 patients (76.3%). The most frequent major toxic effects were myelosuppression, nausea and vomiting.Conclusion: The vindesine with CAP regimen was active combination chemotherapy in patients with locally advanced NSCLC accompanied by the limited side effects.     

紫杉醇脂质体与紫杉醇联合表阿霉素在乳腺癌新辅助化疗中的对照研究

目的　比较紫杉醇脂质体与普通紫杉醇联合表阿霉素两种方案在乳腺癌新辅助化疗中的临床疗效和安全性。方法　本试验采用开放式、随机、对照的方法进行研究。５６例需新辅助化疗的女性乳腺癌患者随机分为紫杉醇脂质体联合表阿霉素组（Ａ组）和普通紫杉醇联合表阿霉素组（Ｂ组）。Ａ组每周期予以紫杉醇脂质体１７５ｍｇ／ｍ^２,Ｂ组每周期予以紫杉醇１７５ｍｇ／ｍ^２,每周期两组表阿霉素均为７５ｍｇ／ｍ２。２１天为１周期,每周期评价毒性反应,２周期化疗后评价疗效。结果　入组病例中Ａ组完成２８例,Ｂ组完成２７例。Ａ组和Ｂ组的总有效率（ＣＲ＋ＰＲ）分别为５３.６％和４８.１％（Ｐ＞０.０５）。两组毒副反应中皮疹、皮肤潮红发生率具有明显差异,以Ａ组较低（Ｐ＜０.０５）;其他如血液学毒性、呕吐、腹泻及发热等基本一致（Ｐ＞０.０５）。结论　紫杉醇脂质体与普通紫杉醇联合表阿霉素方案在乳腺癌新辅助化疗中的疗效相当,但紫杉醇脂质体过敏反应发生率明显低于紫杉醇。     

适形调强放疗联合PF方案同步治疗中晚期食管癌

目的 探讨适形调强放疗（IMRT）联合PF方案同步治疗中晚期食管癌的临床价值。方法 将77例中晚期食管癌患者随机分两组研究。A组采用适形调强放疗＋PF方案化疗,共37例。B组采用常规放疗＋PF方案化疗,共40例。A、B两组均采用PF方案化疗,在放疗第1、5周使用DDP每天30 mg/m²,5-Fu 每天0.5 g/m²,静脉滴注3天,放疗不间断。两组放射剂量均为DT 66Gy,6～7周完成。结果 A组有效率（CR＋PR）89.2%,B组有效率65.0%;A组的1、2、3年生存率为83%、65%、51%,B组的1、2、3年生存率为72%、53%、32%,A、B两组差异均存在明显的统计学意义。χ²分别为7.18和5.53,P均＜0.05。两组的急性放射性食管炎等不良反应基本相同,差异无统计学意义（χ²＝0.08,P>0.05）。但两组的急性放射性肺炎差异有明显统计学意义（χ²＝8.99,P<0.01）。结论 在中晚期食管癌的治疗中,调强放疗联合化疗与常规放化疗联合相比较,具有疗效好、不良反应轻,患者容易耐受等特点,调强放疗在不增加放疗不良反应的同时,能提高靶区的剂量及局控率,降低局部复发率,对总生存率的提高亦有益处。     

Ⅲ期非小细胞肺癌同步放化疗的临床研究

目的比较两种同步放化疗方案对不能手术的Ⅲ期非小细胞肺癌（NSCLC）的疗效及不良反应。方法52例不能手术的Ⅲ期NSCLC患者,随机分成两组,A组每周紫杉醇方案,B组三周紫杉醇＋顺铂（DDP）方案。两组的放疔方法相同,均采用常规分割放疗,每次2．0Gy,每周5次,原发肿瘤灶总剂量60～64Gy。A组在放疗同时给予紫杉醇每周45mg／m^2;B组给予紫杉醇135mg／m^2第1、22天＋DDP30mg／m^2第2天至第4天,第23天至第25天。结果两组的有效率（CR＋PR）分别为78％和74％（P〉0．05）,而两组CR率分别为22％和14％（P〈0．05）。两组1、2、3、5年局部控制率分别为78％、57％、32％、8％和59％、26％、18％、5％,差异有统计学意义（P=0．0493）;1、2、3和5年生存率分别为82％、62％、37％、12％和64％、43％、18％和9％,差异接近具有统计学意义（P=0．0532）。两组重度不良反应差异无统计学意义（P〉0．05）。结论每周小剂量同步放化疗方案可提高NSCLC的局部控制率,并有望延长患者生存时间。     

Induction chemotherapy with carboplatin and ftorafur in advanced head and neck cancer. A randomized study.

From 1987 to 1989, 42 patients with locally advanced squamous cell carcinoma of the head and neck (Stages III-IV, Mo) were randomized to receive radiotherapy (Group A) or three courses of induction chemotherapy followed by radiotherapy (Group B). There were 36 evaluable patients, 17 in Group A and 19 in Group B. The radiotherapy regimen was the same for both groups, 66-74 Gy total tumor doses with standard fractionation scheme of 2 Gy/day. The chemotherapy regimen was a combination of carboplatin 400 mg/m2 by intravenous bolus injection on day 1, and Ftorafur 1,000 mg/m2 orally once a day for 14 days. Cycles were given every 4 weeks. The complete response rate in Group A was 65%; in group B it was 31.5% after induction chemotherapy and 84% after radiotherapy. The 42-month actuarial overall survival rates were 34% for Group A and 47% for Group B (P = NS). Patients from both groups with a complete response had a significantly longer survival time than those with a partial response (P less than 0.001). No significant differences in disease-free survival were found between the two treated groups. The chemotherapy regimen was well tolerated, with moderate hematologic and gastrointestinal toxicity. Increased in radiation toxicity by chemotherapy was not observed.     

Chemo-radiotherapy versus chemo-surgery in stage IIIA non-small cell lung cancer

Forty patients with non-small cell lung cancer stage IIIA, aged 33-72 years were allocated to two groups in order to get therapy of two different combined modalities. All the patients were staged and considered inoperable. Staging was done by bronchoscopy, CT scan, bone scan and in patients with mediastinal lymph nodes less than 2 cm in size by thoracotomy. Group A patients were programmed to have induction chemotherapy and then radiotherapy while patients of group B to have induction chemotherapy, of the same kind as Group A and then surgery. Chemotherapy included cis-platinum 90 mg/m(2) given once every 3 weeks for 4-6 courses. Radiotherapy of Group A patients was 5000 cGy in the primary tumor site and mediastinum. Toxicity was tolerable. The following results were obtained: a) high response rate (over 70%) after chemotherapy, b) 66% of Group B patients were redered operable and c) the survival rate was significantly higher in patients with chemo-surgery versus those with chemo-radiotherapy.     

Cardiotoxicity of high-dose-rate epirubicin evaluated by angiocardioscintigraphy

Cardiotoxicity of high dose rate epirubicin (140-160 mg/m(2) as a bolus every 21 days up to a cumulative dose of 1280 mg/m(2)) was evaluated by angiocardioscintigraphy in 121 patients with advanced neoplastic disease and no preexisting cardiac risk factors. LVEF was measured in each patient before chemotherapy and during the treatment at different epirubicin cumulative dosages. The cases were subdivided into 3 groups: Group A=121 basal studies; Group B=93 studies performed under 800 mg/m(2); Group C=44 studies performed over 800 mg/m(2). A statistically significant decrease of LVEF was observed only at cumulative doses over 800 mg/m(2) (mean LVEF: 53% +/- 11% in Group C vs 64% +/- 7% in Group A). In no case was chemotherapy stopped prematurely and no case of heart failure was observed. A decrease of LVEF 10 units was recorded in 15 patients and 12 of them had been treated with over 800 mg/m(2). No clinical signs of severe cardiac failure were observed in these patients during a follow-up of 5-17 months. In conclusion, epirubicin treatment at high dose rate up to a cumulative dose of 1000 mg/m(2) does not increase the risk of clinically relevant cardiomyopathy and an LVEF decrease of 10 units should not in itself lead to chemotherapy termination in responsive patients.     

Cisplatin, gemcitabine, and vinorelbine combination therapy in advanced non-small-cell lung cancer: a phase II randomized study of the Southern Italy Cooperative Oncology Group.

PURPOSE: In a previous phase I study cisplatin (CDDP), gemcitabine (GEM), and vinorelbine (VNR) combination therapy was safe and very active in patients with non-small-cell lung cancer (NSCLC). This study was aimed at better defining the activity and toxicity of this regimen. PATIENTS AND METHODS: One hundred eleven chemotherapy-naive patients, age < or = 70 years, with stage IIIB or IV NSCLC and a performance status of 0 or 1 (Eastern Cooperative Oncology Group scale) were randomized to two treatment arms. Patients on arm A received CDDP 50 mg/m2, GEM 1,000 mg/m2, and VNR 25 mg/m2 on days 1 and 8 of an every-3-weeks cycle (57 patients). Patients on arm B received CDDP 80 mg/m2, epirubicin 80 mg/m2, and vindesine 3 mg/m2, all delivered on day 1 every 4 weeks, plus lonidamine orally 150 mg three times daily (54 patients). In December 1996, randomization was stopped early, and an additional 30 patients were treated with the experimental regimen to obtain a more accurate estimation of its activity rate. RESULTS: Among 87 patients who received the CDDP-GEM-VNR combination, four complete responses (CRs) and 46 partial responses (PRs) were observed, for an overall response rate of 57% (95% confidence interval [CI], 46% to 68%). Two CRs and 18 PRs were recorded among 54 patients on arm B, giving a 37% activity rate (95% CI , 24% to 51%). After a median follow-up duration of 19 months, the median progression-free and overall survival durations were 32 and 50 weeks in arm A, and 18 and 33 weeks in arm B, respectively. World Health Organization grade 3 to 4 neutropenia and thrombocytopenia occurred in 46% and 14% of patients in arm A and in 22% and 11% of those in arm B, respectively. Severe nonhematologic toxicity was uncommon in both arms. CONCLUSION: The CDDP-GEM-VNR combination is a highly effective treatment for patients with advanced NSCLC and has a manageable toxicity. A phase III trial comparing this new combination with both CDDP-VNR and CDDP-GEM regimens is underway.     

Comparative study on vindesine plus cisplatin treatment of advanced non-small cell lung cancer--three divided doses (35 mg/m2, day 1, 8, 15) and single dose (80 mg/m2, day 1) of cisplatin. Chiba Lung Cancer Study Group]

Sixty-one patients with advanced non-small cell lung cancer were randomly allocated to receive vindesine (3 mg/m2, day 1, 8, 15) plus either three cisplatins (35 mg/m2, day 1, 8, 15) or one cisplatin (80 mg/m2, day 1). Among the 61 patients, the number of complete cases treated by the former administration schedule (group A) was 24 and by the latter schedule (group B) was 27. The response rate of group A was 25.0% and that of group B was 22.2%. There was no significant difference between survival curves of group A and B. The median survival times of group A and B were 8.5 months and 7.5, respectively. Regarding the incidence rate of various side effects, no difference was found between the two groups. However, according to the WHO grade of side effects, nausea/vomiting in group A was significantly milder than in group B. The grade of leukopenia in group A showed a tendency to be milder than in group B. In conclusion, in terms of tumor response, vindesine plus three doses of cisplatin was no better than conventional vindesine plus cisplatin chemotherapy, however side effects of the former were slightly less severe.     

同期减量放化疗与序贯放化疗治疗Ⅲ期非小细胞肺癌的临床试验

目的探讨和比较同期减量放化疗与序贯放化疗治疗不能手术的Ⅲ期NSCLC的毒副反应和近期疗效。方法病理证实为Ⅲa,Ⅲb期（非恶性胸腔积液）不能手术的初治NSCLC患者80例随机分为2组。同期放化疗组（A）：2周期紫杉醇（减半量）＋顺铂（11P）方案化疗,于放疗第一天同期进行。放疗用三维适形放疗,放疗至总量60Gy-70Gy。同期放化疗结束后继续Te（全量）方案巩固化疗3周期。序贯放化疗组（B）：入组后先行放疗,放疗方案同A组,放疗结束后行Te（全量）方案化疗4—5周期。采用WHO近期疗效评价标准和放化疗毒副反应分级标准进行评定。结果A组近期有效率为80．0％,B组为57．5％（x^2=4．71,P〈0．05）,A组Ⅲ,Ⅳ度急性放射性食管炎,白细胞减少,恶心呕吐和皮肤反应发生率分别为47．5％,42．5％,52．5％和57．5％明显高于B组的25．0％,17．5％,30．0％和17．5％（P〈0．05）;A,B组Ⅲ,Ⅳ度急性放射性肺炎,脱发发生率分别为32．5％,7．5％和20．0％,27．5％（P〉0．05）。结论TP方案减量同期放化疗治疗不能手术的Ⅲ期NSCLC,近期疗效较序贯放化疗组高,副反应经积极对症治疗可以耐受。     

Phase I trial of infusional cyclophosphamide, doxorubicin, and etoposide plus granulocyte-macrophage colony stimulating factor (GM-CSF) in non-hodgkin’s lymphoma

PURPOSE: To determine the recommended phase II dose (RPTD) of a 96-h continuous intravenous infusion (CIVI) of cyclophosphamide (200, 300, or 400 mg/m2/d) and etoposide (60 or 90 mg/m2/d) when used in conjunction with doxorubicin (12.5 mg/m2/d) (CDE) given every 28 d plus granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with poor prognosis non-Hodgkin's lymphoma (Group A), and the same regimen given every 21 d (Group B). METHODS: In Group A, infusional CDE was repeated every 28 d, GM-CSF (250 microg/m2) was given subcutaneously from d 6 until neutrophil recovery, with dose escalation in cohorts of three to six evaluable patients. The RPTD of cyclophosphamide and etoposide established in Group A was then used with CDE given every 3 wk (Group B) with GM-CSF given on d 6-20, and dose escalation was attempted again. RESULTS: In Group A, the RPTD of cyclophosphamide and etoposide were 300 mg/m2/d and 90 mg/m2/d, respectively; prolonged neutropenia was the dose-limiting toxicity. In Group B, use of GM-CSF on d 6-20 did not facilitate dose escalation above the RPTD established in Group A. Complete response occurred in 13/26 patients (50%) with no prior chemotherapy, and in 4/16 patients (25%) who had relapsed after prior chemotherapy. CONCLUSIONS: Because of the increase in dose and dose-density afforded by the administration of GM-CSF, the relative dose intensity was increased by twofold for cyclophosphamide (400 vs 200 mg/m2/wk) and etoposide (120 vs 60 mg/m2/wk), and by 1.3-fold for doxorubicin (16.7 vs 12.5 mg/m2/wk).