Phase 1 study of nab-paclitaxel,cisplatin and 5-fluorouracil as induction chemotherapy followed by concurrent chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the oropharynx

BackgroundInduction chemotherapy followed by concurrent chemoradiation (CRT) (sequential therapy) has been evaluated in the treatment of locoregionally-advanced squamous cell cancer of the head and neck (LA-SCCHN), with docetaxel, cisplatin (P) and 5-flurouracil (F) shown to be superior to PF doublet. Nab-paclitaxel (A) is a novel albumin-bound paclitaxel with a superior therapeutic index to docetaxel.MethodsA phase I trial [Clinical trials.gov identifier NCT00731380] to assess the safety and efficacy of nab-paclitaxel + cisplatin + 5-fluorouracil (APF) as induction chemotherapy for three cycles, followed by concurrent carboplatin (area-under-curve (AUC) 1.5 weekly) with radiation therapy (RT) (70 Gy/35 fractions), was conducted using a 3+3 design in patients with previously untreated LA-SCCHN. Dose-limiting toxicities (DLTs) included: standard haematologic and non-haematologic toxicities, treatment delays, inability to complete ⩾95% of RT and skin/mucosal toxicity related to RT assessed from day 1 of treatment to 8 weeks after completion of CRT.Results17 patients with oropharyngeal cancer were enrolled in three dose levels, with 15 patients evaluable for DLT. The median age was 54 years (range, 44–65 years), 14 patients were male, and 11 patients’ tumours were p16 positive and four negative. Grade 3/4 adverse events during APF (%total number of cycles) were hyponatraemia (14%) neutropenia (10%), lymphopaenia (4%) and thrombocytopenia (2%) during 49 evaluable APF cycles. Febrile neutropenia occurred during one cycle of treatment.ConclusionThe recommended phase 2 dose of APF is nab-paclitaxel 100 mg/m² days 1 and 8, cisplatin 75 mg/mg² day 1 and 5-fluorouracil 1000 mg/m²/day × 96 h days 1–4, every 3 weeks, for three cycles prior to CRT.     

TPF方案诱导化疗加同期顺铂化放疗治疗晚期鼻咽癌的临床研究

 目的　探讨多西紫杉醇（TAX）、顺铂（DDP）、5-氟尿嘧啶（5-Fu）三药联合方案诱导化疗加DDP同期放化疗治疗晚期鼻咽癌的近期疗效及可行性。方法　40例初诊局部晚期（UICC分期Ⅲ、Ⅳ期）鼻咽癌患者入组,随机分为诱导化疗加DDP 3周方案组（A组）,诱导化疗加DDP单周方案组（B组）。两组均先行2个疗程诱导化疗,方案为TAX 60 mg／m2第1天;DDP 60 mg／m2第1天;5-Fu 600 mg／m2 第1天至第5天,每3周重复,共2个周期。第7周开始放疗,放疗第1天同时行化疗。A组：DDP 80 mg／m2第1天,每3周1次,共2次;B组： DDP 30 mg／m2第1天,每周1次,共6次。放疗采用二维适形照射,鼻咽原发病灶68～72 Gy,34～36次,7周,颈部淋巴结阳性区60～66 Gy,30～33次,6～6.5周。结果　40例共完成78个疗程诱导化疗,A、B组各1例出组。38例可评价疗效和不良反应。A组17例完成2个疗程同期DDP化疗;B组10例按计划完成6个周同期化疗,4例完成5周化疗,4例完成4周化疗,1例只完成2周化疗。诱导化疗后CR 4例（10.5 %）,PR 27例（71.1 %）,SD 7例（18.4 %）,总有效（CR+PR）率81.6 %。治疗结束后CR 32例（84.2 %）,PR 5例（13.2 %）,SD 1例（2.6 %）,总有效率 97.4 %。结论　TPF诱导化疗加DDP同期放化疗是治疗晚期鼻咽癌的可行方案,推荐使用同期DDP 3周化疗方案。剂量强度可否提高,有待进一步研究。     

Induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal cancer.

BACKGROUND: Since 1990, we have treated patients with advanced nasopharyngeal cancer with induction chemotherapy and concomitant chemoradiotherapy. We herein report the results of our experience. PATIENTS AND METHODS: From 1990 to 1999, 27 patients with locoregionally advanced nasopharyngeal cancer were treated with induction chemotherapy followed by concomitant chemoradiotherapy. Using the American Joint Committee on Cancer's 1992 stage classification, all patients were stage III (11%) or IV (89%). By histology, 63% were poorly differentiated carcinoma and 37% squamous cell carcinoma. The median age was 42 years. Three cycles of induction chemotherapy consisting of cisplatin, 5-fluorouracil, leucovorin and interferon-alpha2b were administered, followed by concomitant chemoradiotherapy consisting of seven cycles of 5-fluorouracil, hydroxyurea and once-daily radiotherapy (FHX) on a week-on week-off schedule. The median radiotherapy dose was 70 Gy. RESULTS: Clinical response to induction chemotherapy was 100%, 54.2% complete response (CR) and 45.8% partial response. Clinical and/or pathological (37% of all patients had post-treatment biopsy with or without neck dissection) CR after FHX was 100%. At a median follow-up of 52 months, three failures were observed. Two patients have died of disease, one of local failure and one of distant metastases. One patient is alive with an isolated rib metastasis. At 5 years, actuarial locoregional control is 93% and actuarial distant control 92%. The overall survival at 3 and 5 years is 88% and 77%, respectively. Four patients died of unrelated illnesses and had no evidence of disease with respect to their nasopharyngeal cancer. The progression-free survival at 3 and 5 years is 92% and 86%, respectively. Thirty-three per cent of patients required a reduction in the chemotherapy dose due to acute toxicity. Chronic toxicity was not observed, with all patients able to eat orally without dietary restrictions. CONCLUSIONS: Treatment of locoregionally advanced nasopharyngeal cancer with induction chemotherapy followed by concomitant chemoradiotherapy resulted in excellent overall survival with acceptable toxicity. These results are encouraging and warrant further investigation of intensified approaches.     

多西他赛加顺铂诱导化疗联合同期放化疗局部晚期非小细胞肺癌的临床观察

目的 评价TP方案诱导化疗联合同期放化疗局部晚期非小细胞肺癌的近期疗效和不良反应。方法 病理证实的局部晚期非小细胞肺癌86例,随机分成同期放化疗联合TP方案诱导化疗(ICCRT) 组和单纯同期放化疗(CCRT) 组。放疗均采用调强放疗。治疗结束后比较两组疗效、生存率和不良反应。结果 86例患者的随访率为100%。ICCRT组和CCRT组的有效率分别为80%和70%(χ²=1.26,P=0.261),1、2、3年总生存率分别为85%和65%、50%和40%、44%和33%(χ²=3.90,P=0.048),主要不良反应白细胞减少(43例和32例,χ²=3.48,P=0.062)、放射性食管炎(26例和20例,χ²=0.12,P=0.730)、血红蛋白减低(26例和16例,χ²=2.34,P=0.126)和放射性肺炎(13例和9例,χ²=0.37,P=0.541)。结论 ICCRT能明显提高局部晚期非小细胞肺癌的总生存率,且与CCRT相比并不增加局部不良反应。     

DPF方案诱导化疗后单药顺铂同期放化疗治疗局部晚期鼻咽癌临床研究

目的评价并比较DPF方案诱导化疗后单药顺铂同期放化疗与单药顺铂同期放化疗治疗局部晚期鼻咽癌的近期临床疗效和毒副反应。方法45例经病理学证实的1Va期初治鼻咽癌患者随机分为对照组和试验组,对照组行单药顺铂同期放化疗,试验组予DPF方案诱导化疗2疗程后行单药顺铂同期放化疗。两组均采用调强适形放射治疗（IMRT）技术。原发肿瘤、阳性淋巴结、高危预防区域和低危预防区域剂量分割分别为70．4—76．4Gy／32—35fx、68Gy／32fx、60—62Gy／30—32fx、54—57Gy／30—32fx。结果试验组和对照组各入组25例和20例,45例患者全部按计划完成治疗。治疗结束后3月复查,试验组96．0％达CR（1例淋巴结残留）;对照组75．0％达CR（鼻咽原发灶残留2例,颈部转移淋巴结残留3例）（P〉0．05）。毒副反应主要是粒细胞减少、胃肠道反应及口腔黏膜炎。诱导化疗期间52．0％发生Ⅲ～Ⅳ度粒细胞减少,28．0％Ⅲ度胃肠道反应,4．O％III度口腔黏膜炎症;同期放化疗期间试验组、对照组发生Ⅲ～Ⅳ度粒细胞减少、Ⅲ～Ⅳ度胃肠道反应、Ⅲ一Ⅳ度口腔黏膜炎分别为68．O％口s25．0％（P〈0．01）、32．O％船30．O％（P〉0．05）、60．O％∞50．O％（P〉0．05）。至中位随访时间13．1月,两组残留病灶均消失,试验组1例（4．O％）出现远处转移,对照组3例（15．O％）出现远处转移（P〉0．05）。结论与单药顺铂同期放化疗治疗局部晚期鼻咽癌相比,DPF方案诱导化疗后单药顺铂同期放化疗增加了粒细胞减少的毒副反应,但可耐受,1年随访局部控制率未获提高,远处转移率降低,但差异无统计学意义。     

Phase II study of combined chemotherapy with docetaxel, CDDP and 5-FU for highly advanced esophageal cancer

Advanced esophageal cancer with widespread metastasis to lymph nodes or other organs is difficult to treat and has an extremely poor prognosis. A new combined chemotherapy of docetaxel with cisplatin (CDDP) and 5-fluorouracil (5-FU) (DPF therapy) was performed and its efficacy and safety were examined. Among those hospitalized between May 2003 and October 2009, 30 patients with stage III or stage IV unresectable, untreated advanced esophageal squamous cell carcinoma which had invaded other organs were enrolled in this study. The regimen of DPF therapy was as follows: a set of intravenous drips of 60 mg/m(2) of docetaxel (day 1), 60 mg/m(2) of CDDP (day 1) and 800 mg/m(2) of 5-FU (days 1-5) was administered twice at an interval of 3 to 4 weeks. Antitumor effects, adverse reactions and treatment outcomes were then examined. The patients included 26 men and 4 women aged 40 to 73 years (average age, 58.1 years), and the performance status (PS) was 1 in 18 cases and 2 in 12 cases. The main location of the esophageal cancer was the upper/middle/lower thoracic esophagus in 7/14/9 cases, respectively. Clinical stage was III in 5 cases and IV in 25. The effective rate of DPF therapy was 83.3% for the primary lesion (complete response, CR: 4 cases, partial response, PR: 21 cases), 72.4% for lymph node metastasis (CR: 3 cases, PR: 18 cases) and 72.0% for distant organ metastasis (CR: 3 cases, PR: 15 cases). The observed adverse reactions of grade 2 or higher of National Cancer Institute-Common Toxicity Criteria (NCI-CTC) included anemia (16.7%), leukopenia (73.3%), liver dysfunction (20.0%), anorexia (16.7%), stomatitis (33.3%), esophagitis (16.7%), alopecia (16.7%) and diarrhea (26.7%). The therapy completion rate was 96.7% and the therapy-related death rate was 3.3%. Treatments given after the completion of the DPF therapy were surgery in 6 cases, chemotherapy such as additional DPF in 12, chemoradiation in 4, esophageal stent placement in 1, and no treatment in 7. The patients' median survival time was 271 days, the 1-year survival rate was 41.9% and the 5-year survival rate was 13.3%. DPF therapy can be used as a standard chemotherapy for advanced esophageal cancer in view of its strong antitumor effect and relatively safe outcome.     

局部晚期鼻咽癌诱导加同期化放疗与诱导化放疗的对照研究

背景与目的：诱导化放疗与同时期化放疗被认为是治疗局部晚期鼻咽癌最有效的两种策略。本随机研究目的在于比较诱导化疗加同时期化放疗与诱导化放疗治疗局部区域晚期鼻咽癌的疗效。方法：从2002年8月到2005年4月,408例患者随机分为诱导化放疗（induction chemoradiotherapy, IC/RT）和诱导加同时期化放疗（induction-concurrent chemoradiotherapy, IC/CCRT）两组。两组患者接受同样的诱导化疗方案：两程氟尿嘧啶脱氧核苷（floxuridine,FuDR）（750mg/m^2,d1-5）＋卡铂（carboplatin,CBP）（AUC=6）,化疗结束后1周行放疗。诱导加同时期化放疗组的患者在在放疗的第7、28、49d接受卡铂AUC=6的化疗。8例不符合人组标准的患者被排除。剩余的400例患者被纳入进行了分析。结果：诱导加同时期化放疗组和诱导化放疗组Ⅲ、Ⅳ度毒性率分别为28．4％和13．1％（P〈0．001）。中位随访3．9年。诱导加同时期化放疗组和诱导化放疗组的3年总生存分别为75．9％和83．4％（P=0．12）。两组的无病生存、局部区域控制和远处转移控制率无统计学差异。结论：本研究采用的诱导加同时期化放疗方案未能较诱导化放疗进一步提高局部区域晚期鼻咽癌患者的总生存率。     

Docetaxel,cisplatin and 5-fluorouracil-based induction chemotherapy followed by intensity-modulated radiotherapy concurrent with cisplatin in locally advanced EBV-related nasopharyngeal cancer

BackgroundThis monocentric study evaluates the activity and tolerability of docetaxel (Taxotere), cisplatin and 5-fluorouracil (5-FU) (TPF) induction chemotherapy followed by intensity-modulated radiotherapy (IMRT) concurrent with high-dose cisplatin in Epstein–Barr virus -related locally advanced undifferentiated nasopharyngeal cancer.Patients and methodsWe retrospectively reviewed the records of patients who received induction docetaxel 75 mg/m² and cisplatin 75 mg/m² on day 1, and 5-FU 750 mg/m²/day (96-h continuous infusion). Following induction, patients received full doses of IMRT concurrently with cisplatin 100 mg/m² every 21 days for three cycles.ResultsThirty patients received three TPF cycles (median). Induction was well tolerated; the main toxicity was neutropenia (33%, grade 3–4). During chemoradiotherapy, neutropenia (40%) and mucositis (43%) were the most frequent grade 3–4 adverse events. Mean dose of IMRT was 68.8 Gy. Worst late toxicity was xerostomia. Complete response rate was 93%. At 35 months, two patients had locoregional recurrence, three had distant metastases, and one had both. Three-year progression-free survival and overall survival were 79% [95% confidence interval (CI) 64% to 94%] and 87% (95% CI 74%– to 100%), respectively.ConclusionsIn this high-stage nonendemic cancer population, TPF followed by high-dose cisplatin IMRT was promising; this treatment approach deserves evaluation in randomized trials.     

Concomitant chemoradiotherapy versus induction docetaxel,cisplatin and 5 fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced head and neck cancer: a phase II randomized study

BackgroundConcomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone.Patients and methodsPatients with stage III–IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m², days1–4, plus 5-fluorouracil 800 mg/m²/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m² and cisplatin 80 mg/m², day 1, and 5-fluorouracil 800 mg/m²/day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6–8 weeks after the end of CT/RT.ResultsA total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms.ConclusionInduction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility.     

TPF方案诱导化疗加同期调强放化疗治疗晚期鼻咽癌的临床观察

目的:探讨TPF方案诱导化疗结合同期调强放化疗治疗局部区域晚期鼻咽癌的有效剂量及近期疗效.方法:Docetaxel与DDP剂量60 mg/m2,静脉滴入;5-FU初始剂量450 mg/(m2·d),持续120 h静脉灌注,按50 mg/(m2·d)剂量递增,根据剂量递增法则确定其最大耐受剂量(MTD),观察终点为出现剂量限制性毒性(DLT).每位患者行3个周期诱导化疗,每个周期化疗间隔3周,第3个周期化疗后3周给予调强放疗(IMRT)加上同期DDP 80 mg/m2化疗.结果:12例患者共完成了450～550 mg/(m2·d)3个剂量水平共34个周期诱导化疗.在550 mg/(m2·d)剂量水平,1例患者出现3度黏膜反应及4度腹泻的DLT,按既定方案再以此剂量依次治疗3例患者,未再发生DLT,该剂量水平即为MTD.除1例DLT患者停止诱导化疗外,余11例患者均行3个周期诱导化疗,3个周期诱导化疗后总反应率(OR)100%,完全缓解率(CR)64%(7/11).12例患者均完成同期放化疗,诱导化疗未加重同期放化疗的毒副反应.结论:TPF方案在Docetaxel 60 mg/m2、DDP 60 mg/m2剂量前提下治疗局部区域晚期鼻咽癌,5-FU的 MTD为550 mg/(m2·d),该方案具有较高近期反应率.     

Randomized study of sinusoidal chronomodulated versus flat intermittent induction chemotherapy with cisplatin and 5-fluorouracil followed by traditional radiotherapy for locoregionally advanced nasopharyngeal carcinoma

Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma (NPC). Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear. This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin (DDP) and 5-fluorouracil (5-FU) followed by radiotherapy in patients with locoregionally advanced NPC. Patients with biopsy-diagnosed untreated stages III and IV NPC (according to the 2002 UICC staging system) were randomized to undergo 2 cycles of sinusoidal chronomodulated infusion (Arm A) or flat intermittent constant rate infusion (Arm B) of DDP and 5-FU fol owed by radical radiotherapy. Using a“MELODIE”multi-channel programmed pump, the patients were given 12-hour continuous infusions of DDP (20 mg/m2) and 5-FU (750 mg/m2) for 5 days, repeated every 3 weeks for 2 cycles. DDP was administered from 10:00 am to 10:00 pm, and 5-FU was administered from 10:00 pm to 10:00 am each day. Chronomodulated infusion was performed in Arm A, with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm. The patients in Arm B underwent a constant rate of infusion. Radiotherapy was initiated in the fifth week, and both arms were treated with the same radiotherapy techniques and dose fractions. Between June 2004 and June 2006, 125 patients were registered, and 124 were eligible for analysis of response and toxicity. The major toxicity observed during neoadjuvant chemotherapy was neutropenia. The incidence of acute toxicity was similar in both arms. During radiotherapy, the incidence of stomatitis was significantly lower in Arm A than in Arm B (38.1%vs. 59.0%, P = 0.020). No significant differences were observed for other toxicities. The 1-, 3-, and 5-year overal survival rates were 88.9%, 82.4%, and 74.8%for Arm A and 91.8%, 90.2%, and 82.1%for Arm B. The 1-, 3-, and 5-year progression-free survival rates were 91.7%, 88.1%, and 85.2%for Arm A and 100%, 94.5%, and 86.9% for Arm B. The 1-, 3-, and 5-year distant metastasis-free survival rates were 82.5%, 79.1%, and 79.1%for Arm A and 90.2%, 85.2%, and 81.7%for Arm B. Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.     

诱导化疗在局部晚期鼻咽癌放射治疗中的价值

目的 :评价诱导化疗对局部晚期鼻咽癌放射疗效的影响。方法 :12 7例病理确诊的Ⅲ、ⅣA期初诊鼻咽癌患者接受诱导化疗 (含顺铂为主的联合方案1～ 3个疗程 )加放射治疗 ,按TNM分期、性别、年龄、病理类型的匹配条件与同期12 7例单纯放疗患者配对进行比较 ,两组采用的放射治疗技术基本一致。结果 :化放组和单放组 3年远处转移率分别为10 2 %和 2 4 4% ,P =0 0 0 3 ,两组的 3年总生存率 (OS)、无瘤生存率 (DFS)、无远处转移生存率 (DMFS)、无复发生存率(RFS)分别为 78 1%和 67 4% ,P =0 0 85 ;72 1%和 63 1% ,P =0 0 47;88 1%和 72 1% ,P =0 0 0 1;84 9%和94 5 % ,P =0 10 5。对N2 ～N3 期患者 ,两组的OS、DFS、DMFS分别为 79 7%和64 9% ,P =0 0 2 7;74 6%和 60 2 % ,P=0 0 14 ;87 9%和 68 6% ,P =0 0 0 2。化放组化疗 2个疗程的 3年DFS要明显高于化疗 1个疗程 ( 83 1%对 65 7% ,P=0 0 49)或单纯放疗 ( 83 1%对 63 1% ,P =0 0 1)。结论 :诱导化疗综合放疗能明显降低局部晚期鼻咽癌患者的远处转移率 ,提高无瘤生存率 ,但不能提高局控率和总生存率 ;诱导化疗力度不足 ( <2个疗程 )将会影响疗效     

Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer.

PURPOSE: To compare the antitumor activity and toxicity of the two induction chemotherapy treatments of paclitaxel, cisplatin, and fluorouracil (FU; PCF) versus standard cisplatin and FU (CF), both followed by chemoradiotherapy (CRT), in locally advanced head and neck cancer (HNC). PATIENTS AND METHODS: Eligibility criteria included biopsy-proven, previously untreated, stage III or IV locally advanced HNC. Patients received either CF (cisplatin 100 mg/m2 on day 1 plus FU 1000 [corrected] mg/m2 continuous infusion on days 1 through 5) or PCF (paclitaxel 175 mg/m2 on day 1, cisplatin 100 mg/m2 on day 2, and FU 500 mg/m2 continuous infusion on days 2 through 6); both regimens were administered for three cycles every 21 days. Patients with complete response (CR) or partial response of greater than 80% in primary tumor received additional CRT (cisplatin 100 mg/m2 on days 1, 22, and 43 plus 70 Gy). RESULTS: A total of 382 eligible patients were randomly assigned to CF (n = 193) or PCF (n = 189). The CR rate was 14% in the CF arm v 33% in the PCF arm (P < .001). Median time to treatment failure was 12 months in the CF arm compared with 20 months in the PCF arm (log-rank test, P = .006; Tarone-Ware, P = .003). PCF patients had a trend to longer overall survival (OS; 37 months in CF arm v 43 months in PCF arm; log-rank test, P = .06; Tarone-Ware, P = .03). This difference was more evident in patients with unresectable disease (OS: 26 months in CF arm v 36 months in PCF arm; log-rank test, P = .04; Tarone-Ware, P = .03). CF patients had a higher occurrence of grade 2 to 4 mucositis than PCF patients (53% v 16%, respectively; P < .001). CONCLUSION: Induction chemotherapy with PCF was better tolerated and resulted in a higher CR rate than CF. However, new trials that compare induction chemotherapy plus CRT versus CRT alone are needed to better define the role of neoadjuvant treatment.     

Phase II study of induction chemotherapy with gemcitabine plus 5-fluorouracil followed by gemcitabine-based concurrent chemoradiotherapy for unresectable locally advanced pancreatic cancer

AIMS AND BACKGROUND: To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. RESULTS: After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). CONCLUSIONS: The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incorporation of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.     

Phase II study of celecoxib with docetaxel chemoradiotherapy followed by consolidation chemotherapy docetaxel plus cisplatin with maintenance celecoxib in inoperable stage III nonsmall cell lung cancer

1 Title

Phase II study of celecoxib with docetaxel chemoradiotherapy (CRT) followed by consolidation chemotherapy docetaxel plus cisplatin with maintenance celecoxib in inoperable stage III nonsmall cell lung cancer.

2 Introduction

Concurrent CRT has been associated with improvement in absolute 5‐year survival by 10% and is the standard of care for inoperable stage III nonsmall cell lung cancer. Preclinical evidence suggests that cyclooxygenase‐2 inhibition may increase the efficacy of CRT.

3 Methods

Patients were treated with CRT (weekly docetaxel at 30 mg/m² over 6 weeks with concurrent external beam radiotherapy with 60 Gy in 30 fractions) followed by consolidation chemotherapy with docetaxel and cisplatin, each at 75 mg/m² given 3 weekly for four cycles. Patients were to receive celecoxib 400 mg twice daily during treatment. Prophylactic cranial irradiation (30 Gy in 15 fractions) was offered if there was disease response.

4 Results

Twenty‐four patients commenced CRT. Nineteen patients commenced consolidation therapy with 14 patients completing treatment. Twelve patients had treatment with celecoxib. In the total cohort, the median overall survival (mOS) was 21 months and progression‐free survival (PFS) was 16 months. Overall response rate was 59% and disease control rate was 82%. Three patient deaths occurred. Significant grade 3/4 toxicity included radiation pneumonitis (17%), febrile neutropenia (17%), infection/sepsis with or with neutropenia (25%) and esophagitis (12.5%). Retrospective analysis of celecoxib versus no celecoxib treatment showed favorable mOS 26.5 versus 17.5 months and PFS 22 versus 16 months, but this did not reach statistical significance.

5 Conclusions

The activity of this regimen has been demonstrated. Treatment‐related toxicity was substantial. The role of celecoxib in addition to CRT could not be demonstrated in this study because of the small number of patients.     

Phase II trial of neoadjuvant docetaxel and cisplatin followed by intensity-modulated radiotherapy with concurrent cisplatin in locally advanced nasopharyngeal carcinoma

Purpose

To evaluate the feasibility and efficacy of neoadjuvant chemotherapy involving docetaxel and cisplatin followed by intensity-modulated radiotherapy (IMRT) with concurrent cisplatin in patients with newly diagnosed stage III to IVB nasopharyngeal carcinoma (NPC).

Methods

Docetaxel (75 mg/m² on day 1) and cisplatin (75 mg/m² on day 1) were administered on a 3-week cycle for 2 courses, followed by radical IMRT (72 Gy/33F/6.5–7 W) with concurrent cisplatin (75 mg/m², on day 1) every 3 weeks for 2 cycles.

Results

From June 2008 to October 2010, forty-six patients were recruited in this trial. Forty-five patients completed neoadjuvant setting, and all patients completed planned concurrent chemoradiotherapy (CCRT). The complete and partial response rates were 28.3 and 56.5 % after neoadjuvant chemotherapy, and 91.3, 8.7 % after CCRT, respectively. After median follow-up of 26 months (range 12–39 months), one patient experienced local recurrence and 4 patients developed distant metastasis. The 3-year overall survival and progression-free survival rate were 94.1 and 72.7 %, respectively. Neutropenia (37.0 %) and vomiting (28.3 %) were the most common Grade 3–4 adverse effects during neoadjuvant course, while mucositis (30.4 %), xerostomia (30.4 %) and radiodermatitis (21.7 %) were the most common Grades 3 acute toxicities during CCRT. Xerostomia (73.9 %), dysphagia (56.5 %), hear loss (30.4 %) and skin reaction (21.7 %) were the common Grade 1–2 late effects. There were no Grades 3–4 late toxicities.

Conclusions

The protocol of neoadjuvant docetaxel and cisplatin followed by IMRT with concurrent cisplatin was well tolerated, with outstanding compliance and efficacy in locally advanced NPC, which deserved further follow-up.     

Experience with combination of docetaxel, cisplatin plus 5-fluorouracil chemotherapy, and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma

Background

Our aim was to evaluate the efficacy and toxicity of cisplatin, fluorouracil, and docetaxel chemotherapy plus intensity-modulated radiotherapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC).

Methods

Sixty patients with locoregionally advanced NPC were enrolled. Patients received IMRT plus three courses of neoadjuvant chemotherapy and two courses of adjuvant chemotherapy consisting of docetaxel (60 mg/m²/day on day 1), cisplatin (25 mg/m²/day on days 1–3), and 5-fluorouracil (500 mg/m²/day on days 1–3).

Results

The overall response rate to neoadjuvant chemotherapy was 89 %. Three months after the completion of radiotherapy, 53 (93 %) patients achieved complete regression, 3 (5 %) achieved partial response (PR), and 1 experienced liver metastasis. However, among the 3 PR patients, 2 patients had no evidence of relapse in the follow-up. With a median follow-up of 27 months (range, 6–43), the 2-year estimated locoregional failure-free survival, distant failure-free survival, progression-free survival, and overall survival were 96.6, 93.3, 89.9, and 98.3 %, respectively. Leukopenia was the main adverse effect in chemotherapy; 14 patients experienced grade 3 or grade 4 neutropenia, and 1 patient developed febrile neutropenia. The nonhematological adverse events included alopecia, nausea, vomiting, anorexia, and diarrhea. The incidence of grade 3 acute radiotherapy-related mucositis was 28.3 %; no grade 4 acute mucositis was observed. No grade 3 or grade 4 hematological toxicity occurred during radiotherapy. None of the patients had interrupted radiotherapy. The common late adverse effects included xerostomia and hearing impairment.

Conclusions

Neoadjuvant–adjuvant chemotherapy using cisplatin, fluorouracil, plus docetaxel combined with IMRT was an effective and well-tolerated alternative for advanced NPC.