局部晚期鼻咽癌洛铂单周方案同期放疗初探

目的 探讨局部晚期鼻咽癌洛铂单药单周方案同期放疗中洛铂最大耐受剂量(MTD)。方法 选择18例Ⅲ-ⅣA期鼻咽癌初治患者,采用根治性IMRT同时进行洛铂剂量递增试验。洛铂初始剂量10 mg/m²,组间递增剂量为5 mg/m²,每个剂量组至少3位受试者。如无剂量限制性毒性反应则进入下一剂量组直至MTD,定期评价疗效及不良反应。结果 10、15 mg/m²剂量组各3例,20、25 mg/m²剂量组6例。25mg/m²组出现2例剂量限制性毒性反应,因此MTD确定为20 mg/m²。患者治疗结束后3个月,鼻咽部肿瘤和颈部阳性淋巴结临床缓解率为100%。主要毒性反应为骨髓抑制。结论 洛铂单药周方案同期放化疗治疗局部晚期鼻咽癌的MTD为20mg/m²,该方案疗效可靠安全性较好,值得开展进一步临床研究。     

局部晚期鼻咽癌调强放疗同期化疗前TPF诱导化疗Ⅰ和Ⅱ期临床研究

目的 探讨局部晚期鼻咽癌调强放疗同期化疗前多西泰索加顺铂加氟尿嘧啶方案诱导化疗中顺铂最大耐受剂量(MTD)及方案安全性、有效性。方法 选取 33例局部晚期鼻咽癌患者,通过剂量递增试验确立顺铂MTD并评价临床疗效及不良反应。结果 多西泰索60 mg/m²第1天、氟尿嘧啶550 mg/m²第 1~5天剂量下顺铂MTD为65 mg/m²第1天,每3周重复下3、4级不良反应发生率分别为中性粒细胞降低 67%,粒细胞缺乏性发热9%,腹泻21%,口腔黏膜炎6%。除剂量限制性毒性患者外,其余均完成了治疗。诱导化疗后有效率为97%,其中完全缓解率为21%。结论 鼻咽癌流行地区每3周重复用多西泰索60 mg/m²第1天、顺铂65 mg/m²第1天、氟尿嘧啶550 mg/m²第 1~5天治疗局部晚期鼻咽癌患者是安全有效的。     

洛铂联合固定剂量多西紫杉醇二线及以上治疗晚期实体肿瘤的剂量递增研究

背景与目的：恶性肿瘤一线化疗后多出现复发或转移,需要二线及以上治疗。本研究旨在确定洛铂联合固定剂量多西紫杉醇治疗化疗后进展的实体肿瘤时洛铂的最大耐受剂量(maximum-tolerated dose,MTD),并评价其不良反应。方法：应用改良的Fibonacci法进行洛铂剂量递增,固定多西紫杉醇剂量为60 mg/m²,洛铂初始剂量为30 mg/m²,组间递增剂量为5 mg/m²,每21天重复。每组至少3例,如1个剂量组中3例均无剂量限制性毒性(dose-limiting toxicity,DLT)出现,则进入下1个剂量组,直至出现DLT,DLT的低一剂量水平即为MTD。结果：17例患者共完成58个周期化疗,进行3个剂量组的研究(洛铂分别为30、35、40 mg/m²),完全缓解(complete response,CR)0例,部分缓解(partial response,PR)1例,疾病稳定(stable disease,SD)10例,疾病进展(progression disease,PD)3例;有效率(response rate,RR,CR+PR)为7.1%(1/14),疾病控制率(disease control rate,DCR,CR+PR+SD)为78.6%(11/14)。主要不良反应为白细胞下降,3例出现DLT,其中2例发生在洛铂40 mg/m²组。确定洛铂35 mg/m²组为MTD。结论：本组洛铂联合固定剂量多西紫杉醇的MTD为35 mg/m²,其不良反应可耐受。     

局部晚期鼻咽癌同期放化疗顺铂单药每周方案剂量递增临床研究

目的:本研究旨在确定每周1次顺铂化疗与常规放疗加后程三维适形放疗同期治疗局部晚期鼻咽癌患者,其顺铂用药的最大耐受剂量(maximum tolerated dose, MTD).方法:选择Ⅲ/ⅣA期局部晚期鼻咽癌初治患者,进行同期放化疗顺铂单药每周方案剂量递增试验,评价治疗不良反应,以出现剂量限制毒性(dose-limiting toxicity, DLT)作为观察终点.顺铂剂量递增范围为15～45 mg·m-2·d-1,每一级剂量水平递增5 mg·m-2·d-1.放疗采用常规放疗加后程三维适形放疗.同期放化疗结束后,评价不良反应和治疗效果.结果: 共入组24例患者,完成每周1次顺铂15～45 mg·m-2·d-1共7个剂量水平的163个用药周期.15～35 mg·m-2·d-1这5个剂量水平的15例患者均未出现DLT, 40 mg·m-2·d-1剂量水平的3例患者中有1例出现Ⅲ度骨髓抑制,45 mg·m-2·d-1剂量水平的3例患者中有3例出现Ⅲ度骨髓抑制,因此确定本研究治疗方案中顺铂的MTD为每周1次40 mg·m-2·d-1.研究中未观察到Ⅳ度不良反应.全组患者治疗结束时,鼻咽部肿瘤和颈部阳性淋巴结临床缓解率为100%.结论:局部晚期鼻咽癌同期放化疗顺铂单药每周方案的MTD为40 mg·m-2·d-1,DLT为骨髓抑制.     

淋巴结阳性食管癌术后预防性IMRT同期化疗的临床Ⅰ期研究

目的 探讨淋巴结阳性食管癌术后预防性IMRT同期化疗的MTD和缩小靶区的影响。方法 对2007—2011年在我院行根治性手术的33例胸中、下段食管鳞癌伴淋巴结转移患者行术后预防性IMRT同期化疗临床Ⅰ期研究。中位年龄52岁,76%为T₃+T₄期。放疗随机分为60 Gy分30次(2.0 Gy/次)18例、54 Gy分30次(1.8 Gy/次)15例。化疗每周顺铂20 mg/m²+紫杉醇20、30、40、50 mg/m²递增(每阶梯3例),连用5~6周。依据CTCAE3.0标准,DLT为4级白细胞下降或≥3级血红蛋白、血小板下降及≥3级非血液学不良反应。结果 60 Gy分30次(2.0 Gy/次)组,紫杉醇20 mg/m²时1例3级体重下降,增加3例后1例4级白细胞降低,递增实验失败。54 Gy分30次(1.8 Gy/次)组1例紫杉醇过敏中止化疗,其余20~40 mg/m²无DLT,50 mg/m²时2例4级白细胞和3级血小板下降而终止实验;MTD为每周顺铂20 mg/m²+紫杉醇40 mg/m²连用5~6周。缩小靶区后60 Gy分30次(2.0 Gy/次)组12例无DLT,顺利完成递增实验;MTD为每周顺铂20 mg/m²+紫杉醇50 mg/m²连用5~6周。靶区修改前、后平均PTV和残胃D_mean差异有统计学意义(P=0.006、0.013)。结论 淋巴结阳性的胸中、下段食管癌术后预防性IMRT同期紫杉醇+顺铂周方案在合理缩小靶区下是安全、有效的。     

宫颈癌同期放化疗每周单药顺铂的Ⅰ和Ⅱ期临床试验

目的 探讨中晚期宫颈癌患者同期放化疗中适合中国人的顺铂单药化疗每周方案剂量。方法 Ⅰ_B2~Ⅳ_A期需放疗的宫颈癌患者为研究对象。Ⅰ期临床试验(15例)为剂量递增试验,顺铂剂量以20、25、30 、35、40 mg/m²逐渐递增(≥3例/剂量),40 mg/m²后不再增加剂量。依据Ⅰ期临床试验所得出的最大耐受剂量(40 mg/m²)进行Ⅱ期临床试验(36例)。盆腔放疗采用三维适形方法。结果 Ⅰ期临床试验剂量递增至顺铂40 mg/m²未出现限制性不良反应。Ⅱ期临床试验中住院的9例患者都完成了6周化疗,门诊治疗的27例患者18例完成6周化疗,19例完成5周化疗,25例完成4周化疗。所有患者都完成了放疗。主要不良反应为1、2级胃肠道反应与白细胞减少。     

不同剂量TP方案化疗联合同步放疗治疗局部晚期食管癌的疗效观察

目的 探讨不同剂量TP方案化疗联合同步放疗治疗局部晚期食管癌疗效及毒副反应。方法 53例局部晚期食管癌患者分成三组:大剂量紫杉醇+顺铂联合放疗组(以下简称大剂量组:DDP 100 mg/m²,d1;PTX 175 mg/m² ,d1)18例;小剂量紫杉醇+顺铂联合放疗组(以下简称小剂量组:DDP 20 mg/m² ,d1-5;PTX 20 mg/m² ,d1、3、5)16例;单纯放疗组19例。化疗21天为1个周期;放疗采用三维适形放疗,常规分割,总剂量60 Gy/6 W。结果 大剂量组、小剂量组、单纯放疗组完全缓解(CR)率、有效率(CR+PR)及1年生存率分别为58.8%、81.3%、26.3%;88.2%、93.8%、57.9%及94.1%、100%、73.7%。三组比较,大、小剂量组CR率、CR+PR率均较单纯放疗组有统计学差异,P＜0.05;小剂量组与单纯放疗组在1年生存率上差异有统计学意义,P＜0.05。毒副反应大剂量组在骨髓抑制、胃肠道反应、脱发,较小剂量组、单纯放疗组差异有统计学意义,P＜0.05。结论 小剂量TP方案化疗联合同步放疗治疗局部晚期食管癌,疗效较好,毒副反应可以耐受。     

局部晚期胃癌术后卡培他滨同期调强放疗的Ⅰ期临床研究

目的 观察局部晚期胃癌术后卡培他滨同期调强放疗(IMRT)中,卡培他滨的最大耐受剂量(MTD)和剂量限制性毒性(DLT)。方法 入组标准为接受根治术(R₀切除)或非根治术(R₁、R₂切除),术后病理证实为T_xN (+) M₀期的近端或远端胃癌患者。共18例患者入组,其中R₀术12例、R₁术2例、R₂术4例。放疗采用IMRT技术,R₀术后总剂量45 Gy,1.8 Gy/次,5 次/周。R₁或R₂术后,对有肉眼或镜下肿瘤残存部位进行局部加量10.8 Gy分6次。卡培他滨剂量水平分5级,分别为625 mg/m²(Ⅰ级)、700 mg/m²(Ⅱ级)、800 mg/m²(Ⅲ级)、900 mg/m²(Ⅳ级)、1000 mg/m²(Ⅴ级),口服2 次/d。结果 最常见1~3级的不良反应为白细胞减少(89%)、食欲下降(83%)和恶心(83%)。Ⅰ级中1例出现3级食欲下降、恶心和4级呕吐。Ⅱ级中1例出现3级食欲下降和恶心。Ⅲ级时2例分别出现4级中性粒细胞减少和3级放射性食管炎。结论 局部晚期胃癌术后卡培他滨同期IMRT的MTD为800 mg/m²,2 次/d,DLT为恶心、呕吐、食欲下降、中性粒细胞减少和放射性食管炎。     

局部晚期鼻咽癌不同化疗方案配合IMRT多中心前瞻性随机对照研究

目的 评价局部晚期鼻咽癌奈达铂联合多西他赛诱导化疗+奈达铂同期IMRT与顺铂的疗效及不良反应。方法 2011—2012年间5个治疗中心共 223例经病理确诊的初治局部晚期鼻咽癌患者被随机分为两组,试验组 113例采用多西他赛(65 mg/m²第1天)+奈达铂(80 mg/m²第1天)诱导化疗2周期,奈达铂(40 mg/m²第1天)每周方案同期IMRT;对照组 110例采用相同方案诱导化疗2周期,IMRT顺铂(40 mg/m²第1天)每周方案同期IMRT。Kaplan-Meier计算生存率并Logrank检验两组差异,不良反应行z检验。结果 随访率为99.1%。治疗结束后3个月两组有效率均为100%,试验和对照组 2年LRFS、RRFS、DMFS、OS分别为94.0%和93.4%、94.2%和94.1%、88.2%和86.7%、90.3%和87.3%(P=0.757、0.478、0.509、0.413);试验组白细胞、中性粒细胞、血小板减少发生率及严重程度较对照组高(P=0.027、0.028、0.035),血红蛋白减少发生率及严重程度低于对照组(P=0.000);试验组恶心、呕吐发生率及程度低于对照组(P=0.023),两组口腔黏膜炎、口干发生率相近(P=0.483、0.781)。结论 局部晚期鼻咽癌奈达铂联合多西他赛诱导化疗+奈达铂同期IMRT的近期疗效与顺铂的相似,胃肠道反应轻患者可耐受,但其骨髓抑制较重使用时应密切监测。     

西妥昔单抗联合同期顺铂化疗加调强放疗局部晚期鼻咽癌的安全性研究

目的 通过开放性、多中心临床研究探讨西妥昔单抗联合同期顺铂化疗加调强放疗(IMRT)局部晚期鼻咽癌的安全性。方法 100例Ⅲ~Ⅳ_b期初治鼻咽癌患者入组,IMRT处方剂量鼻咽原发灶 66.0~75.9 Gy,颈部阳性淋巴结 60~70 Gy;同期顺铂化疗剂量80 mg/m²(每3周);西妥昔单抗首剂400 mg/m²(放疗前,第1周),其后250 mg/m²(每周)。按不良反应常见术语标准3.0版评价这一联合方案的不良反应。结果 全组患者治疗依从性良好。鼻咽原发灶大体肿瘤体积实际中位剂量为69.96 Gy,颈部阳性淋巴结大体肿瘤体积为68 Gy。同期顺铂中位剂量为133 mg/疗程;西妥昔单抗中位起始剂量为690 mg,中位维持剂量为410 mg/周。治疗期间主要不良反应为痤疮样皮疹、口腔黏膜炎以及放射性皮炎,其中1级放射性皮炎及>2级口腔黏膜炎分别占58%、90%,2%患者出现4级口腔黏膜炎。骨髓抑制较为轻微,仅分别有8%、4%和5%患者出现>2级中性粒细胞减少、血小板降低和贫血。结论 西妥昔单抗联合同期顺铂化疗加调强放疗局部晚期鼻咽癌的患者依从性好,不良反应可耐受。     

早期宫颈癌术后每周紫杉醇+顺铂同步3DCRT的Ⅰ期临床研究

目的 明确中国人每周紫杉醇和顺铂同步盆腔放疗早期宫颈癌术后患者的MTD。方法 顺序选择有高中危因素的早期宫颈癌术后患者25例,ECOG≤2。盆腔采用6、10 MV X线4个野3DCRT,照射剂量为40 Gy分20次后予盆腔中央挡铅,宫旁加量10~20 Gy分5~10次;¹⁹²Ir高剂量率腔内照射,参考点为阴道黏膜下0.5 cm,处方剂量为5 Gy/次共2~4次。化疗起始剂量为每周紫杉醇 10 mg/m²、顺铂 20 mg/m²,共6个周期。利用3+3设计方法,每3例患者进行剂量递增直至达到DLT水平。结果 入组患者均在7周内完成外照射和腔内照射。第7剂量组4例患者中2例4周期后出现DLT即3级腹泻。3、4级血液学反应主要为白细胞、中性粒细胞减少,主要发生在4~6周期化疗后。第6剂量组1例出现4级白细胞、中性粒细胞减少,但额外增加的3例未出现4级反应。同步化疗未延迟治疗时间。25例患者中22例完成了6周期化疗。中位随访时间59.5个月,3例患者死于复发转移,1例死于呼吸衰竭。结论 早期宫颈癌术后盆腔照射联合每周紫杉醇和顺铂的同步放化疗安全、耐受性好。中国人的MTD为6周期的每周顺铂35 mg/m²和紫杉醇30 mg/m²。     

Phase I study of twice-weekly gemcitabine and concurrent thoracic radiation for patients with locally advanced non–small-cell lung cancer

Purpose: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity of twice-weekly gemcitabine and concurrent thoracic radiation in patients with Stage IIIa/IIIb non–small-cell lung cancer (NSCLC).

Methods and Materials: Seventeen patients with histologically confirmed Stage IIIa and IIIb NSCLC were studied. Gemcitabine was administered via a 30-min i.v. infusion twice weekly for 6 weeks concurrent with 60 Gy of thoracic radiation. Gemcitabine, starting at a twice-weekly dose of 10 mg/m² (20 mg/m²/week), was escalated in 10–15 mg/m² increments in successive cohorts of 3 to 6 patients until dose-limiting toxicity was observed.

Results: Of the 17 patients entered, 16 were evaluable for toxicity. The dose-limiting toxicity at 50 mg/m² given twice weekly (100 mg/m²/week) was Grade 3 pneumonitis observed in 1 patient, Grade 3 pulmonary fibrosis in a second patient, and Grade 4 esophagitis observed in two additional patients. Twice-weekly gemcitabine at a dose of 35 mg/m² was determined to be the MTD. The overall response rate for the 16 evaluable patients was 88%. The median survival for the entire group is 16.0 months.

Conclusions: The MTD of twice-weekly gemcitabine is 35 mg/m² (70 mg/m²/week) given with thoracic radiation. A Phase II study within the Cancer and Leukemia Group B to ascertain the potential efficacy of this treatment regimen is in development.     

A Phase I Trial of Combination Chemotherapy Employing Carboplatin, Vinca Alkaloids, with or without Bleomycin in Patients with Advanced Malignant Tumors

A Phase I trial of three carboplatin-based combination chemotherapy regimens was conducted. These included: carboplatin plus vindesine; carboplatin, vindesine, plus bleomycin; and, carboplatin plus vinblastine. Carboplatin was administered every 28 days as an intravenous bolus. The initial dose was 150 mg/m² and doses were escalated by 50 mg/m² in each successive group of patients. Vindesine was given at a dose of 3 mg/m² weekly for 5 doses, then every other week thereafter. Bleomycin, 10 units/m² IV bolus, was followed by 10 units/m²/day infusion for 4 days (3-7 and 31-35). Vinblastine was given at 5 mg/m² every other week. Doses of vindesine, vinblastine, and bleomycin were not escalated. The maximum tolerated dose (MTD) of the carboplatin, vindesine bleomycin regimens was reached at a carboplatin dose of 250 mg/m² and the MTD was influenced by the weekly vindesine in the initial 4 weeks of therapy. The MTD of the carboplatin and vinblastine regimen was reached at a carboplatin dose of 500 mg/m². Dose-limiting toxicity of all three regimens was leukopenia. Although nonhematological toxicity of the carboplatin and vinblastine regimen included peripheral neuropathy and emesis, therapy was easily administered in an outpatient setting. The recommended Phase II dose of carboplatin is 450 mg/m² in combination with vinblasrine at this dose and schedule for previously untreated patients. Twelve patients demonstrated major responses with the various regimens including 5 of 24 patients with adenocarcinoma of the upper gastrointestinal tract.     

食管癌同期放化疗中奈达铂剂量递增临床Ⅰ期试验

[目的]探讨在食管癌同期放化疗中多西紫杉醇固定周剂量时奈达铂（NDP）的周最大耐受剂量（MTD）,并观察其不良反应。[方法]共入选20例初治食管鳞癌患者,采用三维适形放疗方法,DT：60～64Gy/30～32f,42～44d,同步化疗方案固定多西紫杉醇剂量20mg/w,共6w,NDP采用周剂量递增方法,起始剂量12mg/m2,递增剂量为6 mg/m2。剂量限制性毒性（DLT）定义为≥3级不良反应,出现DLT的前一剂量即为MTD。[结果]NDP 24mg/m2剂量水平时共有2例患者发生3～4级的DLT;NDP 18mg/m2、多西紫杉醇20mg即为MTD。主要不良反应为放射性食管炎、放射性肺炎、乏力和骨髓抑制。[结论]食管癌同步放化疗中固定多西紫杉醇20mg每周剂量时奈达铂每周最大耐受剂量为 18mg/m2。     

紫杉醇与调强放疗同期治疗鼻咽癌的耐受性试验

背景与目的:各放化疗序贯方式中以同期放化疗对局部晚期鼻咽癌患者的总生存率、局控率以及无远处转移发生率的增益作用最为肯定.临床试验证实,紫杉醇是目前治疗鼻咽癌最为有效的单药之一.本研究的目的在于确定每周1次紫杉醇与调强适形放射治疗(intensity modulated radiation therapy,IMRT)同期使用,治疗局部晚期鼻咽癌患者中紫杉醇的最大耐受剂量(maximal tolerant dose,MTD).方法:局部晚期(Ⅲ/Ⅳa期,'92福州分期)鼻咽癌初治患者入组.治疗相关不良反应按国际常见不良反应标准第3版(CTCAE v3.0)分级,出现剂量限制毒性(doselimiring toxicity,DLT)为观察终点.紫杉醇起始剂量为30 mg·(m2·w)-1,逐级递增10 mg·(m2·w)-1.鼻咽和上颈部靶体积均采用全程IMRT技术照射,下颈部和锁骨上区靶体积采用常规颈前分割野技术照射.IMRT处方剂量鼻咽肿瘤68 Gy分30次照射,颈部转移淋巴结60～66 Gy分30次照射.结果:从2005年4月至2005年9月共入组15例患者,完成了30～60 mg·(m2·w)-14个剂量水平的试验.30 mg·(m2·w)-1和40 mg·(m2·w)-1水平的6例患者均未出现DLT;50 mg·(m2·w)-1水平的3例患者仅1例出现3级口腔粘膜炎并持续4周,按原定试验方案,再以此剂量治疗3例患者,均未发生DLT,试验继续进入下一剂量级别;60 mg·(m2·w)-1水平的3例均出现3级口腔粘膜炎并持续3周以上,剂量递增试验终止.由此初步确定本研究治疗方案中紫杉醇的MTD为50 mg·(m2·w)-1,DLT为口腔粘膜反应,未观察到4级不良反应的发生.血液学不良反应及除口腔粘膜反应外的其他非血液学不良反应均较轻.全组患者治疗结束时鼻咽肿物及颈部转移淋巴结临床缓解率均达100%.结论:口腔粘膜反应是每周使用紫杉醇与IMRT同期治疗局部晚期鼻咽癌的主要DLT,紫杉醇的MTD为50 mg·(m2·w)-1.     

局部晚期胃癌术后替吉奥同期IMRT的Ⅰ期临床研究

目的 观察局部晚期胃癌术后替吉奥同期IMRT中,替吉奥的MTD和DLT。方法 入组标准为接受R₀或R₁切除、术后病理证实为T_xN_1~3M₀期近端或远端胃腺癌患者。术后放疗采用IMRT,R₀术后总剂量45 Gy分25/次5周完成,R₁术后在45 Gy基础上对吻合口进行局部加量10.8 Gy分6次。替吉奥剂量水平分6级,分别为Ⅰ级30 mg/(m²·d)(6例)、Ⅱ级40 mg/(m²·d)(3例)、Ⅲ级50 mg/(m²·d)(6例)、Ⅳ级60 mg/(m²·d)(3例)、Ⅴ级70 mg/(m²·d)(3例)和Ⅵ级80 mg/(m²·d)(6例),于放疗日分2次口服。结果 2010—2013年共 27例患者入组,中位年龄 54岁(29~65岁),男 23例。最常见 1~3级不良反应是恶心(85%)、食欲下降(85%)、白细胞减少(85%)、乏力(70%)和血小板减少(52%)。3级不良反应 4例中 2例为白细胞减少、2例为DLT (3级恶心和食欲下降,Ⅰ级;3级血小板下降,Ⅲ级)。在最高80 mg/(m²·d)水平入组 6例患者均未出现DLT后研究结束。结论 局部晚期胃癌术后替吉奥同期IMRT,替吉奥的MTD为80 mg/(m²·d),于放疗日分2次口服。该剂量被推荐为以后Ⅱ、Ⅲ期研究的剂量水平。DLT为恶心、食欲下降和血小板减少。     

A single-institute phase I/II trial combining nedaplatin dose escalation with a fixed dose of docetaxel for induction chemotherapy of oral squamous cell carcinoma

The purpose of this clinical trial was to assess the toxicity and efficacy of docetaxel plus nedaplatin induction chemotherapy in patients with locally advanced oral squamous cell carcinoma (OSCC). Twenty-one patients were enrolled in this phase I/II clinical study. The toxicities, response rates, and the maximum tolerated dose of nedaplatin that could be safely given preoperatively were assessed. Patients received escalating doses of nedaplatin (60, 70, 80, 90 mg/m²) combined with a fixed dose of docetaxel (60 mg/m²) on day one. Dose-limiting toxicity (DLT), grade 4 leukopenia lasting for two days or more, was seen in one patient at dose level 3; no other DLT was observed at any dose level. The overall response rate was 66.7%. The response rate was 100% at nedaplatin dose level 4, while that at dose level 1 was low (33.3%). Given these results, the recommended dose of nedaplatin in this regimen combined with fixed dose docetaxel (60 mg/m²) was determined to be 90 mg/m². Docetaxel 60 mg/m² plus nedaplatin 90 mg/m² induction chemotherapy can be recommended for patients with locally advanced oral squamous cell carcinoma. Based on these results, an early phase II clinical study using this dose level was conducted; docetaxel plus nedaplatin induction chemotherapy appears to be a useful regimen for the treatment of OSCC. A late phase II clinical study is warranted.     

Phase I trial of outpatient weekly docetaxel, carboplatin and concurrent thoracic radiation therapy for stage III unresectable non-small-cell lung cancer: a Vanderbilt cancer center affiliate network (VCCAN) trial.

PURPOSE: Docetaxel, an active agent for non-small cell lung cancer (NSCLC), has demonstrated activity as a radiosensitizer in numerous pre-clinical studies. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly Docetaxel, Carboplatin with concurrent thoracic radiation therapy (TRT) in patients with unresectable stage III NSCLC. PATIENTS AND METHODS: In this phase I clinical trial, Docetaxel was administered weekly as a 1-h intravenous infusion for 6 weeks with a starting dose of 20 mg/m(2). Docetaxel doses were escalated by 10 mg/m(2) increments in successive cohorts of three patients. DLT was defined as grade >or=3 nonhematologic and hematologic toxicity according to RTOG toxicity criteria. Once the DLT of Docetaxel alone was reached, weekly Carboplatin (AUC 2) was added at a DLT-2 dose of Docetaxel (two dose levels below that of dose limiting toxicity). Docetaxel doses were again escalated at 10 mg/m(2) increments in successive cohorts of three new patients to define further DLT and MTD of Docetaxel/Carboplatin with TRT. TRT was administered to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). RESULTS: Fifteen patients were entered onto this study with Docetaxel alone through three dose escalations (from 20 to 40 mg/m(2) weekly). The DLT of weekly Docetaxel/TRT was esophagitis and the MTD was 30 mg/m(2) per week for 6 weeks. Nine more patients were added with the Docetaxel/Carboplatin/TRT regimen. The DLT of weekly Docetaxel/Carboplatin with TRT was esophagitis and the MTD of Docetaxel was 20 mg/m(2) per week with weekly Carboplatin (AUC 2). There were 2 complete responses and 13 partial responses in 25 evaluable patients (RR 60%). CONCLUSIONS: This combination regimen has activity with manageable toxicity in patients with stage III NSCLC. A phase II study is planned to define activity.