紫杉醇联合顺铂方案同步放化疗及辅助化疗治疗局部晚期鼻咽癌的临床观察

目的:探讨紫杉醇联合顺铂方案同步放疗治疗局部晚期鼻咽癌的临床疗效及不良反应。方法:32例局部晚期鼻咽癌患者,应用紫杉醇120mg/m2,d1、顺铂25mg/m2,d1-3,分别于放疗第1天、第28天给药。放疗结束后第4、7周继续给予紫杉醇135mg/m2,d1、顺铂25mg/m2,d1-3方案辅助化疗。放疗采用Varian直线加速器6MV X射线照射鼻咽及颈部,鼻咽剂量DT 70-76Gy,2Gy/次,共35-38次,颈部剂量DT 60-70Gy,2Gy/次,共30-35次。结果:所有患者均完成放疗,其中22例患者放疗后完成2次化疗,10例患者放疗后完成1次化疗。近期疗效(治疗结束后1个月复查):有效率78.1%,其中CR 2例,PR 23例。远期疗效:3年总生存率为84.4%,鼻咽及颈部3年局部控制率分别为93.8%和96.9%,远处转移率为21.9%。结论:紫杉醇联合顺铂方案同步放疗治疗局部晚期鼻咽癌有助于提高生存率,减少局部复发和远处转移。     

放疗联合化疗及瘤内注射EIB缺失腺病毒(H101)综合治疗鼻咽癌的临床研究

目的:观察放疗联合化疗及瘤内注射EIB缺失腺病毒(H101)综合治疗鼻咽癌的近期疗效和不良反应。方法:符合入选标准的56例鼻咽癌患者先行化疗和同期颈部肿瘤瘤内注射H101,每天1次,每次1支(5×1011病毒颗粒数/0.5 mL),连续5天,化疗用PF方案(DDP 20mg/m2静滴,d 1~d 5,5-FU 500 mg/m2静滴,d 1~d 5),21天为1疗程。连续2疗程后进行放疗。结果:56例鼻咽癌患者放疗结束时肿瘤消退率为71.4%,好转率为28.6%。放疗后3个月肿瘤消退率为100%。放疗后6个月有2例颈部肿瘤复发。不良反应为注射部位局部疼痛19.6%,非感染性发热41.7%,流感样症状8.9%,白细胞下降42.9%,恶心呕吐33.9%,口腔黏膜损害100%。结论:放疗联合化疗及基因治疗鼻咽癌有明确的近期疗效,毒副反应轻,可望成为鼻咽癌新的综合治疗模式,远期疗效有待进一步观察。     

铂类为基础的两种化疗方案治疗中晚期头颈部鳞癌

引言头颈部肿瘤约占全身恶性肿瘤的19.9%~30.2%,头颈部癌的治愈率约为40%~70%。综合治疗目前被认为是治疗中晚期头颈部鳞癌最有效的方法。化疗后放射治疗和/或手术的新辅助化疗,术后或放疗后的辅助化疗,及利用某些化疗药物的放疗增敏作用行同步化放疗,逐步形成了手术、放疗、化疗的综合治疗,以改善局部控制、减少远处转移和提高生存率。目前认为以DDP为基础的联合化疗是治疗中晚期头颈部鳞癌较有效的方案。本文报道了我院2000年1月~2004年1月用DDP+Fudr和DDP+PTX治疗76例中晚期头颈部鳞癌的效果及体会。1资料与方法1.1临床资料2000年1月~2004年1月间入选的76例经病理证实的头颈部鳞状细胞癌初治患者均接受了静脉化疗,男41例,女35例,年龄20~73岁,中位年龄44岁。其中上颌窦癌22例,口腔癌38例,唇癌8例,喉癌8例。根据国际UICC的TNM分期(1991),Ⅲ期28例,Ⅳ期48例。1.2治疗方案A组患者有61例,化疗方案为:Fudr750mg/m2D1~5DDP20mg/m2D1~5B组有15例患者,化疗方案为:PTX135mg/m2D1DDP20mg/m2D2~621天为1周期,...     

序贯化疗联合脑放射治疗非小细胞肺癌脑转移

背景与目的脑放疗是非小细胞肺癌脑转移的传统治疗,化疗与脑放疗的联合是近年的研究方向。鉴于序贯/维持化疗近年来在晚期非小细胞肺癌显示较好前景,我们对非小细胞肺癌脑转移患者进行序贯化疗联合脑放射的治疗探索。方法对确诊的非小细胞肺癌脑转移患者采用TP-NP-GP三个方案序贯化疗联合同期的脑放射进行治疗。TP方案:TXT175mg/m2d1,DDP20mg/m2d1-5,每3周重复;NP方案:NVB25mg/m2d1、8,DDP20mg/m2d1-5,每3周重复;GP方案:GEM1g/m2d1、8,DDP20mg/m2d1-5,每3周重复。每个化疗方案至少使用2疗程,有效的患者继续原方案至4疗程后行下一个方案的序贯化疗。结果51例患者使用TP-NP-GP方案序贯化疗在外周病灶的有效率分别为41.2%、35.6%及27.8%,联合同期的脑放射治疗在脑转移灶的有效率达到60.8%。中位生存期14.7个月。1年、2年及3年生存率分别为67.8%、20.6%及1.3%。结论第三代新药方案序贯化疗联合脑放射治疗非小细胞肺癌脑转移可以取得较好疗效,总体耐受性良好。     

改良FOLFOX方案用于进展期胃癌新辅助化疗的近期疗效

目的:新辅助化疗可以提高进展期胃癌的手术切除率及根治率.本研究旨在评估进展期胃癌行新辅助化疗后的临床疗效.方法:选择2006年9月～2008年9月天津医科大学附属肿瘤医院治疗进展期胃癌患者共80例,分为常规手术组和新辅助化疗+手术组,每组40例.新辅助化疗+手术组患者化疗2个周期,具体方案:奥沙利铂(乐沙定)100mg/m2 iv d1(2h),亚叶酸钙400mg/m2 iv d1(2h).5-Fu 2 400mg/m2 civ d1(46h).每2周为1个周期,共化疗2个周期.化疗后复查CT,了解肿瘤变化后行手术治疗.结果:新辅助化疗十手术组化疗临床有效率(完全缓解+部分缓解)52.5%(21例),疾病稳定37.5%(15例),疾病进展10.0%(4例).手术总切除率92.5%(37/40),获得根治性切除率77.5%(31/40),剖腹探查率7.5%(3/40).常规手术组手术总切除率75.0%(30/40),获得根治性切除率52.5%(21/40),剖腹探查率22.5%(9/40).两组均无手术死亡病例,术后并发症差异无统计学意义.结论:进展期胃癌患者采用改良FOLFOX方案行新辅助化疗具有较高的安全性,并且可以提高手术切除率及根治率以及改善部分患者的临床症状.     

放化疗综合治疗局部中晚期鼻咽癌的疗效观察

目的 探讨诱导化疗+辅助化疗配合放疗综合治疗局部中晚期鼻咽癌的临床疗效和患者的耐受性.方法 于2003年2月至2005年7月,应用 PF方案诱导化疗1周期后3～7d开始行鼻咽癌常规根治性放疗,放疗结束后1w再予以PF方案化疗3个周期,化疗方案:DDP 30mg/m2,静脉滴入,d1～d3 ;5-FU 500mg/m2,静脉滴入,d1～d5,21d为1个周期,观察综合治疗的疗效和患者的耐受性.结果 治疗后3、6个月鼻咽原发病灶完全缓解率分别为95.6%和95.6%,颈部淋巴结完全缓解率分别为93.3%和97.8%.3年总生存率为80%,无进展生存率为73.3%.主要毒副反应为Ⅰ～Ⅱ度消化道反应.Ⅰ～Ⅱ度骨髓抑制发生率较高,主要是白细胞下降,口腔黏膜反应为Ⅰ～Ⅱ级,患者均能耐受.结论 诱导化疗+辅助化疗配合放疗综合治疗局部中晚期鼻咽癌的疗效较满意,毒副反应可以耐受,治疗依从性较好.     

食管癌放疗后复发再程三维适形放疗同步化疗的临床观察

目的:探讨食管癌放疗后复发再程放化疗的价值。方法:48例食管癌放疗后复发患者接受再程治疗。随机分成单纯放疗组(25例)和放化综合治疗组(23例),再程放疗采用三维适形精确放疗技术,6MV X射线,4～5个共面或非共面适形照射野,2.0Gy/次,总剂量46～56Gy。化疗采用多西紫杉醇60～75mg/m2,加入5%GS 250mL静脉滴入,d1;顺铂20mg/m2,加入NS 250mL中静脉滴入,d1～d3;21d为1个周期。结果:单纯放疗组与放化综合治疗组近期局控率分别为80.0%(20/25)和82.6%(19/23),差异无统计学意义,χ2=1.23,P=0.281;单放组1、2和3年生存率分别为52.0%、28.0%和8.0%;放化综合治疗组为56.5%、47.8%和21.7%;差异无统计学意义,χ2=0.89,P=0.269。放化综合组放射性食管炎、放射性肺损伤及Ⅰ～Ⅲ级骨髓抑制发生率分别为47.8%(11/23)、34.8%(8/23)和52.2%(12/23),明显高于单纯放疗组16.0%(4/25)、8.0%(2/25)、16.0%(4/25),差异有统计学意义,χ2值分别为5.65、5.21和7.05,P值分别为0.029、0.033和0.013;死因分析结果显示,单纯放疗组以局部未控(60.0%,15/25)及远处转移(64.0%,16/25)为主,而放化综合组治疗毒副作用导致死亡率明显升高(43.5%,10/23)。结论:三维适形精确放射治疗联合TP方案化疗可作为食管癌放疗后复发患者的有效治疗手段,但应谨慎选择患者。     

NP方案在局部晚期乳腺癌新辅助化疗中的应用

[目的]了解诺维本加顺铂(navelbine/(NVB) cisplatin/(CDDP),NP)的新辅助化疗方案在局部晚期乳腺癌综合治疗中的作用.[方法]23例Ⅱb～Ⅲb期的乳腺癌患者,术前化疗用药为NVB 25mg/m2d1.8 CDDP 25mg/m2d1～3,每3周为一周期,术前用药3周期后评价疗效.[结果]肿瘤原发灶化疗有效率为86.9%,完全缓解(CR)1例,部分缓解(PR)19例,无变化(SD)3例;腋淋巴结临床有效率82.6%,CR 4例,PR 15例,SD 4例.78.3%(18/23)患者可以在3个周期的新辅助治疗后行手术治疗.毒副反应主要为骨髓抑制和消化道反应.[结论]NP方案作为局部晚期乳腺癌新辅助化疗方案有效率高,毒副反应可以耐受.     

局部晚期非小细胞肺癌三维适型放疗同期NP方案化疗的临床分析

目的:评价三维适型放疗联合NP方案同期化疗治疗不能手术切除的局部晚期(ⅢA、ⅢB)非小细胞肺癌(NSCLC)的疗效及毒副反应.方法:86例局部晚期NSCLC患者随机分为三维适型放疗同期化疗组(40例,同期组)及三维适型放疗、化疗序贯治疗组(46例,序贯组),放疗剂量64 Gy,化疗方案为NP方案,长春瑞滨25 mg/m2,静脉滴入,d1、d8;顺铂25 mg/m2,静脉滴入,d1～d3,每3周重复1次.结果:86例全部完成治疗,同期组和序贯组总有效率分别为85.0%(34/40)和76.1%(35/46),P＜0.05;1年生存率分别为67.5%(27/40)和60.9%(28/46),P＜0.05.同期和序贯组Ⅲ～Ⅳ度骨髓抑制分别为22.5%(9/40)和21.7%(10/46),P＞0.05;Ⅱ、Ⅲ级放射肺炎分别为10.0%(4/40)和8.7(4/46),P＞0.05;Ⅱ、Ⅲ期放射性食管炎分别为22.5%(9/40)和19.5%(9/46),P＞0.05.结论:三维适型放疗同期化疗较序贯治疗能明显提高肿瘤的局控率,改善生存率,毒副反应无明显增加.     

紫杉醇联合FOLFOX方案治疗晚期胃癌临床研究

目的:评价紫杉醇联合FOLFOX方案治疗晚期胃癌的疗效及不良反应.方法:35例晚期胃癌患者进入研究,按下列方法治疗:紫杉醇 175mg/m2,分二次d1、d8;奥沙利铂130mg/m2,分2次,d1、d8;亚叶酸钙200mg/m2,静滴2小时,d1;氟尿嘧啶300mg/m2,静推(CF后进行) d1;氟尿嘧啶 500mg/m2,持续输注24小时(氟尿嘧啶静推后进行)d1-3;以上化疗每3周重复.所有病人接受2周期及以上化疗,平均3.2周期.结果:客观有效率为82.2%(29/35),肿瘤进展时间(TTP)为4.5月.主要不良反应为骨髓抑制、恶心、呕吐和口腔炎,没有严重化疗并发症发生.化疗后7例做了手术治疗.结论:紫杉醇联合FOLFOX方案治疗晚期胃癌是可行且有效的方案临床上可有选择地应用.     

甘氨双唑钠(CM-Na)联合同期放化疗治疗中晚期食管癌的Ⅱ期临床研究

背景与目的:同期放化疗是中晚期食管癌的标准治疗方案,但局部控制率及总生存率仍亟待提高。本研究旨在进一步观察乏氧细胞增敏剂甘氨双唑钠(sodiumglyci-didazole,CM-Na)联合同期放化疗治疗中晚期食管癌的近期疗效及不良反应,并评价生存情况。方法:37例中晚期食管癌患者接受同期放化疗及CM-Na增敏治疗。采用常规分割连续照射,总剂量54～64Gy;同期化疗予顺铂20mg·(m2·d)-1加氟尿嘧啶500mg·(m2·d)-1,连续静脉滴注5天,分别于放疗第1、4周实行。根据Ⅰ期临床研究推荐剂量,采用CM-Na700mg·(m2·d)-1,每周一、三、五于放(化)疗前1h内给药。结果:治疗结束后3个月复查时,CR16例(43.2%),PR17例(46.0%),总有效率为89.2%。随访结果显示,本组患者的中位生存时间23.2个月,1年、2年总生存率分别为78.6%与48.7%。Ⅲ度不良反应发生率21.6%,以血液系统为主,经临床干预不影响治疗进程;未发现神经系统毒性。结论:在Ⅰ期临床研究推荐剂量下,CM-Na联合同期放化疗对提高中晚期食管癌临床缓解率及生存率有一定意义。     

Inflammatory breast cancer outcome with epirubicin-based induction and maintenance chemotherapy: ten-year results from the French Adjuvant Study Group GETIS 02 Trial

BACKGROUND: The authors evaluated the long-term efficacy and side effects in patients with nonmetastatic, unilateral, inflammatory breast cancer (IBC) who received homogeneous treatment with intensive induction chemotherapy followed by a maintenance regimen. METHODS: One hundred twenty patients were randomized to receive high-dose fluorouracil, epirubicin, and cyclophosphamide (FEC-HD) (fluorouracil 750 mg/m(2) on Days 1 to 4, epirubicin 35 mg/m(2) on Days 2 to 4, and cyclophosphamide 400 mg/m(2) on Days 2 to 4 for 4 cycles every 21 days) with or without lenograstim. Locoregional treatment consisted of surgery and/or radiotherapy. Maintenance chemotherapy was FEC 75 (fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) on Day 1 every 21 days for 4 cycles). No hormone treatment was allowed. RESULTS: The safety of the FEC-HD regimen was described previously. Among 102 patients who underwent surgery, a pathologic complete response (pCR) was achieved by 23.5% of patients with breast tumors and by 31.4% of patients with involved axillary lymph nodes. The overall pCR rate was 14.7%. One hundred nine patients received FEC 75. After a median 10 years of follow-up, the disease-free survival (DFS) and overall survival (OS) rates were 35.7% and 41.2%, respectively. The median DFS was 39 months (95% confidence interval [95% CI], 25-53 months), and the median survival was 61 months (95% CI, 43-79 months). Five patients developed a temporary decrease in left ventricular ejection fraction without congestive heart failure. In the lenograstim group, 1 patient developed acute myeloblastic leukemia M2, and 1 patient developed myelodysplastic syndrome. CONCLUSIONS: FEC-HD induction chemotherapy followed by FEC 75 maintenance regimen had moderate and acute long-term toxicities and lead to high DFS and OS rates in patients with IBC.     

Will high dose chemotherapy followed by autologous bone marrow transplantation supplant cranio-spinal irradiation in young children treated for medulloblastoma?

Cranio-spinal irradiation is the gold standard treatment used in non metastatic medulloblastoma as prophylaxis against central nervous system (CNS) metastases. However, given the severe late effects caused by this procedure in children under 3 years of age, most pediatric oncologists are currently treating these patients with conventional chemotherapy in order to postpone or even avoid irradiation. In the French Society of Pediatric Oncology ('FOP) this attitude has been adopted since 1987.Among the patients treated without radiotherapy, 20 relapsed while on conventional chemotherapy and were entered in a study of high-dose chemotherapy (HDC) followed by ABMT. Their median age at diagnosis was 23 months (R5-71) and the relapse occurred at a median time of 6.3 months after the initiation of chemotherapy. Complete surgical removal of the local relapse was the first treatment in 4/20 patients who were not evaluable for response. Sixteen of the twenty patients had measurable disease at the primary site (9 patients), or at metastatic sites (3 patients) or both (4 patients). The conditioning regimen consisted of combination Busulfan 600 mg/m² over 4 days and Thiotepa 900 mg/m² over three days. After recovery from aplasia, patients with a local relapse received local radiotherapy limited to posterior fossa. Results. Among the 16 patients with measurable disease, 6 CR, 6 PR, 3 NR, were observed following HDC (response rate 75 %). One patient was not evaluable. For the 20 patients, the EFS is 50%. Among the surviving patients, the median follow up is 31 months post BMT (R12-82). Ten patients who developped a local relapse or local progression are alive with NED without craniospinal irradiation. Among the 7 patients who developped metastases or progression of metastases, only one is alive. Toxicity was high but manageable: the median duration of granulocytopenia < 0.5 × 109/1 and thrombocytopenia < 50 × 10⁹/1 was 13 and 41 days respectively. Bacteremia was documented in 4 cases. Grade > 2 mucositis and diarrhea were observed in 60% of patients. One complication-related death occurred 1 month post BMT. Conclusion. With a 75 % response rate, this HDC proved to be very efficient in relapsed medulloblastoma. A longer follow up is necessary to demonstrate whether, after a local relapse, HDC could replace craniospinal irradiation as prophylaxis against CNS metastases.     

Combined modality therapy for primary CNS lymphoma.

PURPOSE: Primary CNS lymphoma (PCNSL), formerly rare, is being seen with increased frequency among apparently immunocompetent patients. Conventional treatment has consisted of whole-brain radiotherapy (RT) and corticosteroids, with a median survival of 15 to 18 months and a 3% to 4% 5-year survival. Chemotherapy has been useful in the treatment of recurrent PCNSL. In 1985 we began a treatment protocol using chemotherapy and cranial irradiation for the initial therapy of non-AIDS PCNSL. PATIENTS AND METHODS: Thirty-one patients (group A) completed the combined modality regimen. All had placement of an Ommaya reservoir and received pre-RT systemic methotrexate, 1 g/m2, plus six doses of intra-Ommaya methotrexate at 12 mg per dose. A full course of cranial RT (4,000-cGy whole-brain RT plus a 1,440-cGy boost) was followed by two cycles of high-dose cytarabine (ara-C), with each course consisting of two doses of 3 g/m2 ara-C separated by 24 hours and infused over 3 hours. During this period, 16 additional patients (group R) were treated with RT alone, either because patients refused chemotherapy or RT was initiated before our consultation; all would have been eligible to participate in the protocol. Follow-up extended through April 1, 1991. RESULTS: Group A had a significantly prolonged time to recurrence (median, 41 months) compared with group R (median, 10 months; P = .003). Although median survival was doubled from 21.7 months for group R to 42.5 months for group A, this was not statistically significant because of small sample size. More importantly, group R patients received systemic chemotherapy for recurrent PCNSL, which improved survival. CONCLUSION: The addition of chemotherapy to cranial RT for initial treatment of PCNSL significantly improved disease-free survival and contributed to overall survival; all non-AIDS patients with newly diagnosed PCNSL should be considered for combined modality therapy.     

Multimodality therapy for medulloblastoma

Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting of vincristine, BCNU, dexamethasone and intrathecal and intermediate dose intravenous methotrexate (500 mg/m2). Five also received local low dose radiotherapy (RT). All 8 patients responded to treatment; 6 completely and 2 partially. These latter 2 were in their second and third recurrences. Three remain in remission. The median duration of response was 18.8 months, and median time from start of chemotherapy to death was 32 months using the Kaplan-Meier technique. In addition, 9 other patients with newly diagnosed medulloblastoma were treated with craniospinal radiation and the same adjuvant chemotherapy as above. The first 5 patients also received intraventricular methotrexate and/or intravenous BCNU during radiotherapy. The toxicity in the 5 patients was very severe. There were three toxic deaths, one death from cancer; one patient survives disease-free, but he is demented. With the discontinuance of intraventricular methotrexate and the postponement of myelo-suppressive chemotherapy until after the completion of radiotherapy, the regimen has been well tolerated. All 4 patients treated this way remain alive, well, and disease-free at intervals up to 36 months. We conclude that recurrent medulloblastomas are sensitive to multiagent chemotherapy and that prolonged remissions may occur. With primary adjuvant chemotherapy, extreme caution with myelo-suppressive drugs must be exercised during the period of craniospinal radiotherapy. We also do not recommend the use of intraventricular methotrexate. When these two criteria were followed, the preliminary results with adjuvant chemotherapy appear encouraging.     

Concurrent Cisplatin-etoposide Chemotherapy plus Thoracic Radiotherapy for Limited-stage Small Cell Lung Cancer

A recent approach in the treatment of limited-stage small celllung cancer (LDSCLC) has involved a combined modality of chemotherapyand chest irradiation. In using the modality, the study of schedulingmethods for combining chemotherapy and radiotherapy should leadto other trials of combined modalities against LDSCLC sinceit is the most basic issue to be evaluated. We have thus conducteda multicenter phase II trial of concurrent cisplatin-etoposide(PVP) chemotherapy and radiotherapy for LDSCLC to determinethe effects of the concurrent administration of a PVP regimenand chest irradiation on response rate, relapse, survival andtreatment toxicity. The chemotherapy regimen consisted of afour-week cycle: cisplatin (80 mg/m², given intravenously onday 1) and etoposide (100 mg/m2, given intravenously on days1–3). This cycle was given four to six times within sixmonths. Chest irradiation to the primary tumors at both thehili and the mediastinum was administered in standard fractionson days 2–12 in the first cycle of chemotherapy and ondays 29–47 in the second cycle, with a total dose of 40–50Gy. Prophylactic cranial irradiation was performed among completeremission (CR) or good partial remission (PR) patients aftercompletion of the concurrent therapy. A total of 66 patientswere entered into the trial and 59 were evaluated. The concurrenttherapy induced an overall response rate of 94.9% in 59 patients:24 patients, 40.7% CR, 32 patients, 54.2% PR. The median responseduration was 8.7 months, and the median survival time for alleligible patients was 14.8 months. The percentage of patientswith two-year survival periods was 20. A local relapse withinthe irradiated area was seen in only 22% of relapsed patients.Brain metastases occurred in 24% of patients. Four of 32 patientstreated with prophylactic cranial irradiation had brain metastases.Toxic effects, chiefly grades 3 and 4 leukopenia, as establishedby the World Health Organization, were detected in all treatedpatients. Other toxicities, including radiation-induced esophagitisand pneumonitis, were deemed almost acceptable. We concludedconcurrent treatment of a PVP regimen with chest irradiationto be a feasible and beneficial therapy with an efficacy compatibleto that of other published reports. The outcome of this protocolwarrants further investigation to determine the optimal typeof schedule for concurrent chemoradiotherapy against LDSCLC.     

Alternating chemotherapy and accelerated split-course irradiation in locally advanced nonsmall cell lung carcinoma.

BACKGROUND: The prognosis of patients with locally advanced nonsmall cell lung carcinoma (NSCLC), which is usually unresectable, is very poor, and patient survival rarely reaches 1 year. However, prolonged survival correlated with objective responses has been observed among patients with intrathoracic disease treated with a combination of cytotoxic drugs and local irradiation despite the lack of consensus regarding the schedule of such combined therapy. From October 1989 to November 1993, a Phase II study was conducted to evaluate the tolerability and efficacy of alternating chemotherapy and accelerated split-course radiotherapy in the treatment of patients with locally advanced NSCLC. METHODS: Sixty-three consecutive patients with unresectable Stage III NSCLC entered this study. The treatment was composed of 3 cycles of combined chemotherapy and radiotherapy at 4-week intervals. Chemotherapy with cisplatin (30 mg/m2/day) and etoposide (100 mg/m2/day) was delivered intravenously on Days 1, 2, and 3, followed by radiotherapy on Days 4-8. A course of radiotherapy consisted of 1.5 gray (Gy) per fraction twice a day (3 Gy per day) for 5 consecutive days, for a total dose of 15 Gy. Response was assessed after 3 courses, for a total irradiation dose of 45 Gy. In cases of objective antitumoral response with operable tumor, surgery was performed. A fourth course of chemotherapy and radiotherapy, for a total dose up to 60 Gy in 12 weeks, was administered to all patients. Two additional courses of chemotherapy were given, for a total of six. RESULTS: Of the 63 patients, 62 were evaluable for response. Six had a complete remission and 36 a partial response, resulting in an overall response rate of 67.7%. Nine patients underwent surgery (pneumonectomy for seven patients and lobectomy for two patients), and the complete disappearance of any residual tumor was documented histologically in four. Of the 290 chemotherapy courses delivered, there were 31 of Grade 3-4 toxicity, mainly leukopenia and vomiting. The median times of freedom from disease progression and overall survival were 8 months (confidence interval [CI], 7-9.5) and 14 months (CI, 10-22), respectively. The 1-, 2-, and 5-year survival rates of the 62 patients were 54%, 35%, and 21%, respectively. Patients who responded had a significantly longer median survival (16 months) than nonresponders (7 months) (P = 0.02). However, there was no difference in the survival of resected and nonresected patients. CONCLUSIONS: This treatment schedule resulted in a high response rate with prolonged survival. However, the toxicity of this approach was not negligible, even though it did not preclude this strategy. This combined modality must be compared with other combinations of alternating or sequential chemoradiotherapy.     

Induction chemotherapy with carboplatin-paclitaxel followed by standard radiotherapy with concurrent daily low-dose cisplatin plus weekly paclitaxel for inoperable non-small-cell lung cancer

Both induction chemotherapy and concurrent platinating agents have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study investigated activity and feasibility of a novel chemoradiation regimen, including platinum and paclitaxel, both as induction chemotherapy and concurrently with thoracic radiotherapy. Previously untreated patients with histologically/cytologically proven unresectable stage I-III NSCLC were eligible. Induction chemotherapy consisted of 2 courses of 200 mg/m2 paclitaxel and carboplatin at AUC of 6 mg/mL/min every 3 weeks. From day 43, continuous thoracic irradiation (60 Gy in 30 fractions radiotherapy for 6 weeks) was given concurrently with daily cisplatin at a dose of 5 mg/m2 intravenously and weekly paclitaxel at a dose of 45 mg/m2 for 6 weeks. Fifteen patients were accrued in the first stage of the trial. According to the previous statistical considerations, accrual at the second stage of the study was halted as a result of the achievement an insufficient number of successes. Major toxicity of combined chemoradiation was grade III-IV esophagitis requiring hospitalization for artificial nutrition, which occurred in 58% of patients. Other toxicities included grade II-IV fatigue in 75% of patients and grade I-IV neuromuscular toxicity in 67%. Only 7 patients completed the treatment program as scheduled. Eight patients (53.3%; 95% confidence interval, 26.5-78.7%) had a major response (5 partial response, 3 complete response), 2 patients had disease progression, and 1 was stable at the end of treatment. Four patients died early. With a median follow up of 38 months, the median survival was 12 months. A combined chemoradiation program, including platinum and paclitaxel, appears difficult to deliver at full dose as a result of toxicity, mainly esophagitis. More active and less toxic combined modality treatments need to be developed for inoperable NSCLC.     

Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas

BACKGROUND: The role of high dose chemotherapy (HDC) in patients with pediatric brain tumors currently is ill-defined. The purpose of this pilot study was to assess the feasibility and the benefit of HDC after radiotherapy in a group of children with newly diagnosed diffuse pontine gliomas. METHODS: Patients eligible for study were ages 3-18 years with diffuse intrinsic tumors arising in the pons, who were not treated previously with radiotherapy or chemotherapy. Histologic confirmation was not mandatory, provided clinical findings and magnetic resonance imaging were typical. Patients were given focal radiotherapy followed 2-3 months later by HDC. Busulfan (150 mg/m(2) on Days 8, 7, 6, and 5) and thiotepa (300 mg/m(2) on Days 4, 3, and 2) were administered prior to autologous bone marrow transplantation. Survival was the endpoint, and the statistical procedure was based on sequential subgroup analysis. RESULTS: Thirty-six patients were entered on to the study, 12 of whom underwent stereotactic biopsy or open surgery at the time of diagnosis. One patient eventually was excluded due to inappropriate eligibility criteria. All 35 eligible patients received irradiation. Early progression (9 patients) and parental refusal (2 patients) precluded the use of HDC in 11 patients. Three patients died of HDC-related complications. All 21 patients who survived HDC eventually died of disease progression. The median survival time was 10 months for the study group. The median survival time in the subgroup of patients who received HDC was 10 months (range, 3-26 months). Statistical analysis did not suggest any evidence of survival benefit. CONCLUSIONS: For patients with diffuse pontine gliomas, survival using this aggressive treatment modality does not appear to be any better than that reported for conventional radiotherapy.     

Feasibility of four consecutive high-dose chemotherapy cycles with stem-cell rescue for patients with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor after craniospinal radiotherapy: results of a collaborative study.

PURPOSE: This study was designed to determine the feasibility and safety of delivering four consecutive cycles of high-dose cyclophosphamide, cisplatin, and vincristine, each followed by stem-cell rescue, every 4 weeks, after completion of risk-adapted craniospinal irradiation to children with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor (PNET). PATIENTS AND METHODS: Fifty-three patients, 19 with high-risk disease and 34 with average-risk disease, were enrolled onto this study. After surgical resection, high-risk patients were treated with topotecan in a 6-week phase II window followed by craniospinal radiation therapy and four cycles of high-dose cyclophosphamide (4,000 mg/m2 per cycle), with cisplatin (75 mg/m2 per cycle), and vincristine (two 1.5-mg/m2 doses per cycle). Support with peripheral blood stem cells or bone marrow and with granulocyte colony-stimulating factor was administered after each cycle of high-dose chemotherapy. Treatment of average-risk patients consisted of surgical resection and craniospinal irradiation, followed by the same chemotherapy given to patients with high-risk disease. The expected duration of the chemotherapy was 16 weeks, with a cumulative cyclophosphamide dose of 16,000 mg/m2 and a planned dose-intensity of 1,000 mg/m2/wk. RESULTS: Fifty of the 53 patients commenced high-dose chemotherapy, and 49 patients completed all four cycles. The median length of chemotherapy cycles one through four was 28, 27, 29, and 28 days, respectively. Engraftment occurred at a median of 14 to 15 days after infusion of stem cells or autologous bone marrow. The intended dose-intensity of cyclophosphamide was 1,000 mg/m2/wk; the median delivered dose-intensity was 1,014, 1,023, 974, and 991 mg/m2/wk for cycles 1 through 4, respectively; associated median relative dose-intensity was 101%, 102%, 97%, and 99%. No deaths were attributable to the toxic effects of high-dose chemotherapy. Early outcome analysis indicates a 2-year progression-free survival of 93.6% +/- 4.7% for the average-risk patients. For the high-risk patients, the 2-year progression-free survival is 73.7% +/- 10.5% from the start of therapy and 84.2% +/- 8.6% from the start of radiation therapy. CONCLUSION: Administering four consecutive cycles of high-dose chemotherapy with stem-cell support after surgical resection and craniospinal irradiation is feasible in newly diagnosed patients with medulloblastoma/supratentorial PNET with aggressive supportive care. The early outcome results of this approach are very encouraging.