Induction chemotherapy with paclitaxel plus carboplatin followed by paclitaxel with concurrent radiotherapy in stage IIIB non-small-cell lung cancer (NSCLC) patients: a phase II trial

PURPOSE: We conducted a prospective phase II trial to evaluate the efficacy and toxicity of induction chemotherapy with paclitaxel plus carboplatin followed by concurrent radiotherapy with weekly paclitaxel in stage IIIB non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Patients with stage IIIB NSCLC received two 3-week cycles of paclitaxel 200mg/m(2) combined with carboplatin (target area under the plasma concentration curve (AUC) of 6 mg/ml) followed by weekly paclitaxel 50mg/m(2) concurrently with radiotherapy consisted of 2 Gy daily, 5 days per week (60 Gy total dose in 6 weeks). The median follow-up period was 5 years. RESULTS: Between March 1999 and January 2002, 21 patients were enrolled and analyzed. Ninety percent of patients completed the planned treatment schedule. The overall response rate was 76% (24% complete response and 52% partial response). The median overall survival time was 15 months and the 1-year, 2-year and 5-year overall survival rates were 57, 33 and 24%, respectively. The disease progression rate at 1 year was 43% and the median progression-free survival was 8 months. During the chemoradiation period, grade 3-4 oesophagitis and pneumonitis were observed in 24 and 14% of patients, respectively. CONCLUSIONS: Induction chemotherapy with carboplatin and paclitaxel followed by weekly paclitaxel with concurrent radiotherapy was found to be active and tolerable in selected stage IIIB NSCLC patients. Further studies are needed to improve the safety profile and outcome in this setting.     

诱导化疗和紫杉醇每周同期化疗结合三维适形放射治疗不能手术的Ⅲ期非小细胞肺癌的初步结果

背景与目的:局部晚期非小细胞肺癌(non-smallcelllungcancer,NSCLC)单纯放疗局部控制率差,放化疗综合治疗及放疗剂量递增成为提高局控的主要研究方向,但最佳治疗模式尚未确定。本研究观察诱导化疗和三维适形放射治疗(three-dimensionalconformalradiotherapy,3DCRT)联合每周紫杉醇治疗NSCLC的毒性及初步疗效。方法:Ⅲ期NSCLC患者予紫杉醇(175mg/m2,d1)加卡铂(AUC=5～6,d1)诱导化疗2～4疗程,化疗后3～4周内开始3DCRT,剂量在满足V20≤31%,脊髓≤50Gy的条件下给予尽可能的高,联合每周紫杉醇40mg/m2同期化疗。结果:31例患者入组,诱导化疗毒性可耐受。同期放化疗期间,3例因3～4度急性毒性中止治疗,2例因身体虚弱分别中断治疗7天及12天,其余26例按计划完成治疗。白细胞下降发生率为51.6%(16/31,1例为3度,余为1～2度);3度淋巴细胞下降发生率达67.7%(21/31)。主要急性毒性为放射性食管炎和放射性肺炎,3度放射性食管炎3例,3～4度放射性肺炎2例。1～4度后期食管损伤各有1例发生;肺纤维化均不超过2度。肺原发灶总有效率(CR PR)为74.1%(CR1例,PD2例)。中位生存时间18.5个月,1、2、3年生存率分别为74.2%、41.9%、34.6%,中位局部无进展生存时间为14.3个月,1、2、3年局部无进展生存率分别为64.5%、32.3%、20.5%。结论:诱导化疗后3DCRT结合每周紫杉醇治疗局部晚期NSCLC能为大多数患者耐受,初步疗效令人鼓舞。     

A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small-cell lung cancer (a Vanderbilt Cancer Center Affiliate Network Study)

PURPOSE: We conducted a prospective phase II study to determine the response rate, toxicity, and survival rate of concurrent weekly paclitaxel, carboplatin, and hyperfractionated radiation therapy (paclitaxel/carboplatin/HFX RT) followed by 2 cycles of paclitaxel and carboplatin for locally advanced unresectable non-small cell lung cancer (NSCLC). The weekly paclitaxel and carboplatin regimen was designed to optimize the radiosensitizing properties of paclitaxel during the concurrent phase of treatment. METHODS AND MATERIALS: Forty-three patients with unresectable stage IIIA and IIIB NSCLC from the Vanderbilt Cancer Center and Affiliate Network (VCCAN) institutions were entered onto the study from June 1996 until May 1997. Weekly intravenous (IV) paclitaxel (50 mg/m(2)/l-hour) and weekly carboplatin (AUC 2) plus concurrent hyperfractionated chest RT (1.2 Gy/BID/69.6 Gy) were delivered for 6 weeks followed by 2 cycles of paclitaxel (200 mg/m(2)) and carboplatin (AUC 6). RESULTS: Forty-two patients were evaluable for response and toxicities. Three patients achieved a complete response (7.2%) and 30 patients achieved a partial response (71.4%), for an overall response rate of 78.6% [95% C.I. (66.2%-91.0%)]. The 1- and 2-year overall and progression-free survival rates of all 43 patients were 61.6% and 35% respectively, with a median survival time of 14.3 months. The median follow-up time was 14 months. Esophagitis was the principal toxicity. Grade 3 or 4 esophagitis occurred in 11 patients (26%). There was an incidence of 7% grade 3 and 9.5% grade 4 pulmonary toxicities. CONCLUSIONS: Weekly paclitaxel, carboplatin, plus concurrent hyperfractionated RT is a well-tolerated outpatient regimen. The response rate from this regimen is encouraging and appears to be at least equivalent to the more toxic chemoradiation trials. These findings warrant further clinical evaluation of weekly paclitaxel/carboplatin/HFX RT in a phase III study.     

Phase II study of radiotherapy with three-dimensional conformal boost concurrent with paclitaxel and cisplatin for Stage IIIB non-small-cell lung cancer

PURPOSE: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy with paclitaxel/cisplatin for Stage IIIB locally advanced non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Radiotherapy was administered to a total dose of 70.2 Gy (daily fraction of 1.8 Gy, 5 days/wk), over an 8-week period, combined with chemotherapy. The chemotherapy consisted of weekly 40 mg/m2 of paclitaxel plus 20 mg/m2 of cisplatin for 8 consecutive weeks. All patients received three-dimensional conformal radiotherapy (3D-CRT), based on computed tomography simulated planning after 41.4 Gy. The median follow-up period of survivors was 24 months. RESULTS: Between January 2000 and October 2002, 135 patients with a median age of 60 years were enrolled and analyzed in this prospective trial. The overall response rate was 75% including 2 cases of complete response. The major patterns of failure were local failure and distant metastasis. The 2-year overall and progression-free survival rates were 37% and 18%, respectively. The median overall and progression-free survival times were 17 months and 9 months, respectively. Hematologic toxicity >Grade 2 was observed in 19% of patients and severe non-hematologic toxicity was infrequent. CONCLUSIONS: Three-dimensional conformal radiotherapy, combined with paclitaxel and cisplatin chemotherapy, was associated with a satisfactory outcome with manageable toxicity. Further investigations are needed to improve the local control.     

新辅助化疗和三维适形放疗同期化疗治疗局部晚期非小细胞肺癌临床近期疗效分析

目的：采用新辅助化疗和三维适形放疗（3DCRT）同期化疗综合治疗不能手术的局部晚期非小细胞肺癌（NSCLC）,探讨最佳治疗方式。方法：Ⅲ期非小细胞肺癌予以紫杉醇加卡铂新辅助化疗2—4疗程,化疗后4周开始放疗（3DCRT）,并联合每周紫杉醇60mg／m^2同期化疗。结果：32例入组患者新辅助化疗不良反应可耐受。同期放化疗期间,主要急性不良反应为白细胞下降,放射性肺炎和放射性食管炎。后期不良反应主要是肺纤维化和食管损伤,均可耐受。肺原发病灶总有效率为76．2％。3年随访,中位生存时间为18．8月,3年生存率40．2％,中位局部无进展生存时间为15．3月,3年局部无进展生存率25％。结论：新辅助化疗和三维适形放疗同期每周紫杉醇化疗治疗局部晚期非小细胞肺癌患者可耐受,疗效较好,可临床推广。     

A phase II trial of concurrent chemoradiation therapy followed by consolidation chemotherapy with oral etoposide and cisplatin for locally advanced inoperable non-small cell lung cancers

We report a phase II study to evaluate the survival rate, response rate and toxicity of concurrent chemoradiation therapy (CCRT) followed by consolidation chemotherapy (CT) with oral etoposide and cisplatin for patients with locally advanced inoperable non-small cell lung cancer (NSCLC). Fifty-four patients with locally advanced inoperable NSCLC who had received no prior therapy were enrolled into this trial between May 1995 and December 2000. Treatment consisted of two cycles of concurrent CT and four cycles of consolidation CT with oral etoposide (50 mg/m2) on days 1-14 during the CCRT courses and on days 1-21 during the consolidation CT courses, plus cisplatin (75 mg/m2 i.v.) on day 1 of a 28-day cycle. Conventional radiotherapy (1.8 Gy/fraction, 63 Gy over 7 weeks) was delivered from day 1 of the CT. Fifty-two patients were evaluable for response. Twelve patients (22%) achieved complete responses, and 32 patients (60%) achieved partial responses, for an overall response rate of 82% with a median duration of response of 9.1 months. Forty-three per cent developed grade 4 haematological toxicity, 11% grade 3 or 4 oesophagitis and 7% grade 3 or 4 lung toxicity. There were two treatment-related deaths, one from radiation pneumonitis and the other from sepsis. After a median follow-up duration of 50 months (range 20-85), the median overall survival time was 15.3 months (95% CI, 9.7-20.8), and the 1-, 2-, 3-, and 5 year overall survival rates were 62, 40, 30 and 16%, respectively. The duration of median progression-free survival was 12.3 months (95% CI, 7.4-17.3), and the 1-, 2-, 3-, and 5-year progression-free survival rates were 47, 40, 29 and 23%, respectively. Thus, concurrent conventional chest radiotherapy with oral etoposide plus cisplatin followed by consolidation CT led to an encouraging survival rate and prolongation of the time to progression, with moderate toxicity in patients with locally advanced inoperable NSCLC.     

紫杉醇卡铂周方案同步化疗联合三维适形放射治疗局部晚期非小细胞肺癌的临床研究

目的观察紫杉醇卡铂周方案同步化疗联合三维适形放疗(3D-CRT)治疗局部晚期非小细胞肺癌(NSCLC)的毒性反应及疗效。方法采用前瞻性非随机对照方法,将52例局部晚期NSCLC患者分为同步组(21例):采用紫杉醇和卡铂周方案化疗联合同步3D-CRT;序贯组(31例):采用紫杉醇和卡铂序贯化疗联合3D-CRT。同步组紫杉醇40 mg/m2,静脉滴注1h;卡铂AUC 1.5。序贯组在放疗前行2周期的紫杉醇和卡铂辅助化疗,紫杉醇150 mg/m2,第1天、第21天;卡铂AUC 5,第1天、第21天。3D-CRT 1.8～2.0 Gy/d,总剂量60～66 Gy/6～8周。结果52例患者全部完成治疗。有12例患者在治疗过程中由于白细胞减少而导致治疗时间延长1周以上,其中同步组5例,序贯组7例。同步组中,肺原发灶完全缓解(CR)为9.5%(2/21),部分缓解(PR)为71.4%(15/21),无变化和进展(NC PD)为19.0%(4/21),有效率(CR PR)为81.0%。序贯组中,肺原发灶CR为6.5%(2/31),PR为67.7%(21/31),NC PD为25.8%(8/31),CR PR为74.2%。同步组和序贯组患者的Ⅱ～Ⅲ级急性放射性食管炎、Ⅱ～Ⅲ级急性放射性肺炎和Ⅱ～Ⅲ级白细胞减少发生率分别为61.9%(13/21)和41.9%(13/31)、23.8%(5/21)和22.6%(7/31)及42.9%(9/21)和19.4%(6/31)。同步组有1例患者出现Ⅳ级白细胞减少。52例患者的中位生存时间为17.5个月(同步组19.0个月,序贯组15.8个月),1、2年总生存率分别为72.0%和37.0%,1、2年局部控制率分别为75.0%和75.0%。结论同步放化疗是一种安全有效的治疗方法,绝大多数患者能耐受治疗。同步组与序贯组相比,有提高有效率和延长生存率的趋势,但差异并无统计学意义。     

Concurrent hyperfractionated radiotherapy and low-dose daily carboplatin and paclitaxel in patients with stage III non-small-cell lung cancer: long-term results of a phase II study.

PURPOSE: To investigate the feasibility and activity of hyperfractionated radiation therapy (Hfx RT) and concurrent chemotherapy (CT) consisting of low-dose, daily carboplatin and paclitaxel in patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Sixty-four patients started their treatment on day 1 with 30 mg/m(2) of paclitaxel administered by 1-hour infusion. Hfx RT began on day 2 using 1.3 Gy bid to a total dose of 67.6 Gy and concurrent low-dose daily CT consisting of 25 mg/m(2) of carboplatin and 10 mg/m(2) of paclitaxel, both given Mondays to Fridays during RT course. RESULTS: Objective response rate was 83% and included complete response in 27 patients (42%) and partial response in 26 patients (41%). Ten patients (16%) had stable disease, whereas only one patient (2%) had progressive disease. The median survival time was 28 months, and 3- and 5-year survival rates were 37% and 26%, respectively. The median time to local progression was 26 months, and 3- and 5-year local progression-free survival rates were 37% and 33%, respectively. The median time to distant metastasis was 25 months, and 3- and 5- year distant metastasis-free survival rates were 37% and 31%, respectively. Acute high-grade (>/= grade 3) toxicity was hematologic (25%), esophageal (17%), bronchopulmonary (13%), and skin (9%). Late high-grade toxicity was infrequent. CONCLUSION: This combined Hfx RT/TC regimen produced results that are among the best ever reported and warrants further study in a prospective randomized fashion.     

不可手术局部晚期NSCLC隔周恩度联合同步放化疗多中心五年生存分析

目的:评价隔周使用重组人血管内皮抑制素(恩度)联合以铂类为基础同步放化疗治疗不可手术局部晚期非小细胞肺癌(NSCLC)患者的5年生存情况。方法:2009—2015年间来自两项前瞻性研究的115例患者[2009—2012年临床试验(ClinicalTrials.gov,编号NCT01218594)和2012—2015年的...     

Phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer

We conducted a phase II trial to investigate the efficacy of concurrent chemoradiation in patients with stage III non-small-cell lung cancer (NSCLC). Thirty patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Patients received six weekly cycles of paclitaxel 45 mg/m(2) over 1 h; carboplatin at (area under the curve) AUC 2; and radiation therapy of 60 Gy. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy over 4 weeks) followed by a boost to the primary tumor (20 Gy in 2 weeks). After the initial phase of concurrent chemoradiation, patients received an additional four cycles of paclitaxel 175 mg/m(2) over 3 h and carboplatin at AUC 6 every 3 weeks. The overall objective response rate of 30 assessable patients was 76.7%. At the median follow-up time of 13.1 months, the median survival time was 14.5 months (95% CI, 10.59-18.48). The median progression-free survival was 10.5 months (95% CI, 7.72-13.28). The major toxicity was hematologic. The incidence of grade 3 esophagitis was 10%. In conclusion, this chemoradiation regimen is well tolerated and shows significant clinical results for locally advanced NSCLC. Locoregional failure rate remains an important issue with this newer chemotherapeutic regimen. A novel chemotherapy and radiation therapy is clearly needed.     

大分割放疗在局部晚期或晚期非小细胞肺癌中的疗效

目的 探讨难以行常规分割放疗的局部晚期/晚期非小细胞肺癌(NSCLC)患者,45Gy分15次大分割放疗的近期疗效和不良反应。方法 回顾性分析2014—2018年间天津医科大学肿瘤医院 64例无法手术的局部晚期/晚期NSCLC患者。使用Pinnacle 9计划系统设计计划,并采用调强放疗或容积旋转调强放疗行胸部大分割放疗(45Gy分15次)。探讨其近期疗效、生存率和不良反应。结果 中位随访时间为26个月。在可评价的 58例患者中 2例(3%)完全缓解,22例(38%)部分缓解,28例(44%)疾病稳定,6例(9%)疾病进展,局部控制率为90%。中位复发时间、总生存期分别为8.2、21.0个月,1、2、3年复发率分别为37%、28%、14%,总生存率分别为66%、43%、27%。放疗期间 11例(17%)急性食管炎,12例(19%)急性肺炎,13例(20%)骨髓抑制,未发现≥3级食管炎和肺炎。结论 45Gy分15次大分割放疗在局部晚期/晚期NSCLC中安全有效,不良反应可控。     

常规放疗结合每周紫杉醇治疗局部晚期鼻咽癌Ⅱ期临床试验

[目的]探讨常规放疗结合每周紫杉醇治疗局部晚期鼻咽癌的长期疗效。[方法]局部晚期（Ⅲ～Ⅳa期）鼻咽癌患者在常规放疗的同时每周给予30mg／m。的紫杉醇化疗。[结果]38例患者,鼻咽部放疗平均剂量71．1Gy;颈部转移淋巴结放疗平均剂量60．3Gy;30例患者完成7次,7周化疗。1例因急性反应过大只完成4次化疗,还有2例和5例分别完成5次和6次化疗。未观察到明显胃肠道反应和严重血液学毒性。总有效率（CR＋PR）84．2％,中位随访时间52个月。累积1年生存率为94．7％,2年生存率86．7％,3年生存率69．9％,4年生存率58．7％．5年生存率53．1％。[结论]常规放疗结合每周紫杉醇治疗局部晚期鼻咽癌耐受性较好,疗效满意。     

局部晚期非小细胞肺癌VMAT初步疗效和不良反应分析

目的 评估VMAT用于局部晚期非小细胞肺癌(NSCLC)放疗近期疗效和不良反应。 方法 2016年间无法手术的局部晚期NSCLC患者共 58例接受同步放化疗或序贯放化疗,其中男 47例。放疗剂量为 38~66 Gy,53例(92%)患者放疗剂量≥56 Gy。放疗中位次数30次,单次剂量 1.8~3.0 Gy。28例(48%)患者接受同步化疗。 结果 中位随访时间9个月,1年总生存率84%,1年无进展生存48%。11例(19%)患者发生症状性放射性肺炎,其中1例患者因为放射性肺炎死亡。31例(53%)患者在放疗后半年内CT发现无症状性肺局部纤维化。17例(29%)患者出现2级食管炎,10例(17%)患者发生≥3级不良反应,其中9例为白细胞减少。 结论 采用VMAT行局部晚期NSCLC胸部放疗近期疗效理想,不良反应可接受,肺炎风险未见增加。     

Integrating concurrent navelbine and cisplatin to hyperfractionated radiotherapy in locally advanced non-small cell lung cancer patients treated with induction and consolidation chemotherapy: feasibility and activity results

OBJECTIVES: The purpose of this study was to determine the effectiveness and toxicity of a new combination schedule based on concurrent navelbine, cisplatin and hyperfractionated radiotherapy in patients with locally advanced NSCLC treated with platinum and gemcitabine induction and consolidation chemotherapy. MATERIALS AND METHODS: The 37 patients with pathological confirmed advanced NSCLC (non-surgical stages IIIA and IIIB) were included in the study. All of them were assessable for survival and 32 for response. The treatment schedule consisted of cisplatin (100 mg/m2) or carboplatin (400 mg/m2) on day 1 with gemcitabine (1000 mg/m2) on days 1, 8 and 15. Treatment was given every 28 days for two courses, followed by concurrent administration of accelerated modified hyperfractionated radiotherapy, with concomitant boost, with a total dose of 61.64 Gy administered for 5 weeks, with cisplatin and navelbine, for two courses, finally followed by two courses of the same initial chemotherapy. RESULTS: Four patients achieved complete response (12.5%) and 14 (44%) partial response, for an overall objective response rate of 56.5%. After a minimum follow-up duration of 35.5 months, median progression free survival was 12.2 months. The median survival was 15.4 months with actuarial 1-, 2- and 3-year survival of 67, 21 and 15%, respectively. The main toxicity was hematological. There was esophagitis (grades III and IV) in 30% of the patients and there were two treatment-related deaths. CONCLUSION: Combined treatment with concurrent radiotherapy and chemotherapy in non-surgical NSCLC is an acceptable treatment modality. However, the toxicity was not negligible.     

Paclitaxel and concurrent radiation for locally advanced pancreatic cancer

Purpose: To determine the activity and toxicity of paclitaxel and concurrent radiation for pancreatic cancer.

Methods and Materials: Forty-four patients with locally unresectable pancreatic cancer were studied. Patients received paclitaxel, 50 mg/m² by 3 h i.v. (IV) infusion, weekly, on Days 1, 8, 15, 22 and 29. Radiation was administered concurrently to a total dose of 50.4 Gy, in 1.80 Gy fractions, for 28 treatments.

Results: Nausea and vomiting were the most common toxicities, Grade 3 in five patients (12%). Two patients (5%) had Grade 4 hypersensitivity reactions to their first dose of paclitaxel. Of 42 evaluable patients, the overall response rate was 26%. The median survival was 8 months, and the 1-year survival was 30%.

Conclusion: Concurrent paclitaxel and radiation demonstrate local-regional activity in pancreatic cancer. Future investigations combining paclitaxel with other local-regional and systemic treatments are warranted.     

单药顺铂在局部晚期鼻咽癌同步放化疗中的临床应用分析

目的：评价局部晚期鼻咽癌PDD同步化疗的疗效及毒副反应。方法：52例局部晚期鼻咽癌接受顺铂同步放疗,PDD化疗的第1天就开始实施同步放疗,顺铂30 mg/m2静脉滴注,每周1次,共7次;鼻咽部病灶及阳性的淋巴结给予放疗总量为70Gy,颈部预防性照射给予放疗量50Gy,每周5次,每次2Gy。结果：全部患者均可评价,近期有效率为100%;1年、3年和5年OS分别为100%、88.5%、25%;3年、5年的无病生存率分别为80.8%和19.2%;平均生存时间和中位生存时间分别为48.7月和47月。无病平均生存时间和无病中位生存时间分别为45.7月和45月。结论：局部晚期鼻咽癌含PDD方案的CCRT有较好的疗效,毒性反应可耐受,长期生存需要进一步观察。     

紫杉醇加顺铂同步放化疗治疗局部晚期食管癌的临床研究

目的:探讨紫杉醇加顺铂(TP)同步放化疗治疗局部晚期食管癌的疗效及毒副反应。方法:48例局部晚期食管癌患者,随机分成两组,每组24例,A组为单纯放疗组,B组为每周紫杉醇加顺铂同步放化疗组。两组均采用6MV或者18MVX射线放射治疗,食管癌原发灶剂量60～68Gy,区域淋巴结剂量50～60Gy。B组放疗同时给予紫杉醇40mg/m2 DDP20mg/m2,均于d1、d8、d15、d22、d29、d36静滴。结果:单纯放疗组和紫杉醇加顺铂组的有效率(CR PR)分别为75%和88%,差异有显著性意义(P<0.05)。两组的1、3、5年局部无进展生存率分别为60.7%、21.0%和9.5%,71.2%、49.3%和19.2%,两组局部无进展生存率差异有显著性意义(P=0.034);两组的1、3、5年生存率分别为66.7%、25.0%和12.5%,79.2%、58.3%和29.2%,总生存率差异有显著性意义(P=0.041)。同步放化疗组的Ⅲ、Ⅳ级毒副反应高于单纯放疗组。结论:同步放化疗可提高局部晚期食管癌的无进展生存率和总生存率,但毒副反应有增加的趋势。     

Daily low-dose cisplatin plus concurrent high-dose thoracic radiotherapy in elderly patients with locally advanced unresectable non-small-cell lung cancer

There are few prospective studies of concurrent chemoradiotherapy in elderly patients with locally advanced unresectable non-small-cell lung cancer (NSCLC), although the therapy has proved superior to radiotherapy alone for the treatment of younger patients. We conducted a pilot study to assess the tolerance and efficacy of concurrent cisplatin and thoracic radiation in elderly patients with locally advanced unresectable NSCLC. Eligible patients were more than 71 years old and had unresectable Stage I, II, or III NSCLC. Cisplatin was administered at 6 mg/m2 daily intravenously on days 1 through 5, days 8 through 12, days 29 through 33 and days 36 through 40. Beginning day on 1, thoracic radiation was delivered at 2.0 Gy daily to a total dose of 60 Gy. Twelve patients were registered and 11 were eligible. Patient characteristics were ages of 73 to 80 years, and stage III A (18%) and stage III B (73%) NSCLC. The most common grade 3 toxicities included leukopenia (20%) and thrombocytopenia (9%). Grades 3/4 elevation of serum creatinin, esophagitis and pneumonitis did not occur. The overall confirmed response rate was 82%, and median overall survival was 23 months. The 2-year survival rate was 53%. This chemoradiotherapy regimen is well tolerated with promising response and survival in elderly patients with unresectable NSCLC.     

Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage IIIB non-small cell lung cancer

BACKGROUND: To evaluate feasibility and safety of induction three-drugs combination chemotherapy and concurrent radio-chemotherapy in stage IIIB NSCLC. PATIENTS AND METHODS: Patients with stage IIIB NSCLC were treated with three courses of induction chemotherapy, cisplatin 50 mg/m(2), paclitaxel 125 mg/m(2) and gemcitabine 1000 mg/m(2) on days 1,8 of every 21 day cycle. Patients without distant progressive disease were then treated with radiotherapy and concurrent weekly gemcitabine (250 mg/m(2)). Toxicity and response of radio-chemotherapy treatment have been assessed. RESULTS: Between Jan 01 and Nov 02, 46 patients were enrolled. Grade 3+ hematological and non-hematological toxicity during the induction phase were 41.3% and 13.1%, respectively. In 38 patients a Clinical Response or Stable Disease was recorded and these patients underwent to concurrent radio-chemotherapy. Grade 3+ hematological and non-hematological toxicities were 8.2% in this group. Further response was observed in 66% of patients. Overall median survival time was 17.8 months, with a 3-year survival rates of 23%. CONCLUSION: Three-drugs induction chemotherapy and concurrent radio-chemotherapy with weekly gemcitabine in locally advanced stage IIIB NSCLC is feasible and safe.     

Induction carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal thoracic radiation therapy in unresectable stage IIIA/B nonsmall cell lung carcinoma: a modified Phase I trial

BACKGROUND: A modified Phase I trial was conducted evaluating the incorporation of 3-dimensional conformal radiation therapy (3DCRT) into a strategy of sequential and concurrent carboplatin/paclitaxel in Stage III, unresectable nonsmall cell lung carcinoma (NSCLC). In addition, dose escalation of thoracic conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was performed. Endpoints included response rate, toxicity, and survival. METHODS: Twenty-nine patients with unresectable Stage III NSCLC were included. Patients received 2 cycles of induction carboplatin (AUC 6) and paclitaxel (225 mg/m(2)/3 hours) every 21 days. On Day 43, concurrent TCRT and weekly (x6) carboplatin (AUC 2) and paclitaxel (45 mg/m(2)/3 hours) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts. RESULTS: The response rate to induction carboplatin/paclitaxel was 52%. Three patients (10%) experienced disease progression during the induction phase. No dose-limiting toxicity was seen during the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was esophagitis, with 18% of patients developing Radiation Therapy Oncology Group Grade 3 esophagitis. The overall response rate was 70% (1 complete response and 18 partial responses). Survival rates at 1 and 2 years were 69% and 45%, with a median survival of 21 months. The 1-year progression free survival probability was 41% (95% confidence interval, 23-59%). CONCLUSIONS: Incorporation of 3DCRT with sequential and concurrent carboplatin/paclitaxel is feasible, and dose escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall response and survival rates are encouraging. Accrual is continuing in a Phase II fashion at 74 Gy with sequential and concurrent carboplatin/paclitaxel.