Does paclitaxel improve the chemoradiotherapy of locoregionally advanced esophageal cancer? A nonrandomized comparison with fluorouracil-based therapy.

PURPOSE: A phase II trial of accelerated fractionation radiation with concurrent cisplatin and paclitaxel chemotherapy was performed to investigate the role of the paclitaxel, when substituted for fluorouracil (5-FU), in the chemoradiotherapy of esophageal cancer. PATIENTS AND METHODS: Patients with an esophageal ultrasound stage of T(3) or N(1) or M(1) (nodal) esophageal cancer were treated with two courses of a cisplatin infusion (20 mg/m(2)/d for 4 days) and paclitaxel (175 mg/m(2) over 24 hours) concurrent with a split course of accelerated fractionation radiation (1.5 Gy bid to a total dose of 45 Gy). Surgical resection was performed 4 to 6 weeks later followed by a single identical postoperative course of chemoradiotherapy (24 Gy) in patients with significant residual tumor at surgery. Toxicity and results of this treatment were retrospectively compared with our previous 5-FU and cisplatin chemoradiotherapy experience. RESULTS: Between September 1995 and July 1997, 40 patients were entered onto this study. Although dysphagia proved worse in our 5-FU-treated patients, profound leukopenia and a need for unplanned hospitalization were significantly more common in the paclitaxel group. Thirty-seven patients (93%) proved resectable for cure. The 3-year projected overall survival is 30%, locoregional control is 81%, and distant metastatic disease control is 44%. When compared with a similarly staged cohort of 5-FU-treated patients, there was no advantage for any survival function studied. CONCLUSION: This paclitaxel-based treatment regimen for locoregionally advanced esophageal cancer produced increased toxicity with no improvement in results when compared with our previous 5-FU experience. Paclitaxel-based treatments must be carefully and prospectively studied before their incorporation into the standard management of esophageal cancer.     

Phase I trial of Orzel (UFT plus leucovorin), cisplatin, and radiotherapy in the treatment of potentially resectable esophageal cancer

PURPOSE: Fluorinated pyrimidines have been established as radiosensitizers in the combined modality therapy of esophageal cancer. UFT, an oral combination of a 5-fluorouracil pro-drug (uracil) and a dihydropyrimidine dehydrogenase inhibitor (ftorafur), may provide improvement in the ease of administration with equal efficacy. This Phase I study was designed to determine the maximal tolerated dose and dose-limiting toxicity of UFT, leucovorin, and cisplatin when given with radiotherapy in the neoadjuvant treatment of resectable esophageal cancer. METHODS: Chemotherapy consisted of i.v. cisplatin 80 mg/m(2) (Days 1 and 22) and UFT with leucovorin orally on Days 1-35. UFT was escalated in 50-mg/m(2) increments, starting at 200 mg/m(2)/d. Radiotherapy consisted of 4500 cGy in 25 fractions. Patients underwent resection 4-6 weeks after chemoradiotherapy. RESULTS: Ten patients with resectable esophageal cancer were enrolled. Of the 7 patients entered at dose level 1, 1 developed a dose-limiting toxicity of nausea. All 3 patients entered at dose level 2 developed dose-limiting toxicity. The maximal tolerated dose for UFT was the starting level, 200 mg/m(2)/d. Of the 10 patients enrolled, 8 underwent esophagectomy and 2 developed progressive disease and did not undergo surgery. The disease of 6 of the 8 patients was downstaged at surgery. CONCLUSION: The recommended UFT dose for Phase II studies is 200 mg/m(2)/d given orally in two divided doses when given with leucovorin, cisplatin, and radiotherapy.     

Mature survival results with preoperative cisplatin,protracted infusion 5-fluorouracil,and 44-Gy radiotherapy for esophageal cancer

PURPOSE: To assess the long-term survival results after cisplatin, protracted infusion 5-fluorouracil, and concurrent radiotherapy (RT) followed by surgical resection of esophageal cancer. METHODS AND MATERIALS: Ninety-two patients with esophageal cancer (65 with adenocarcinoma and 27 with squamous cell carcinoma) were treated in two sequential protocols of preoperative chemoradiotherapy. The patients had tumor confined to the esophagus and regional nodes, including celiac nodes for middle and distal lesions. In trial A (1989-1994), 50 patients were treated with 44 Gy RT (2 Gy/d) along with concurrent 5-fluorouracil 300 mg/m(2)/d given by protracted venous infusion on Days 1-30 and cisplatin 26 mg/m(2) on Days 1-5 and 26-30. In trial B (1995-1997, 42 patients), the chemotherapy dosages during RT were reduced to 5-fluorouracil 225 mg/m(2)/d protracted venous infusion and cisplatin 20 mg/m(2)/d on Days 1-5 and 16-30; three cycles of paclitaxel 135 mg/m(2)and cisplatin 75 mg/m(2) were given postoperatively. Surgery generally occurred 4-6 weeks after completion of the planned preoperative therapy. Transhiatal resection was performed whenever possible. RESULTS:Of the 92 patients, 86 (93%) underwent surgery (1 refused, 2 died preoperatively, and 3 developed evidence of metastatic disease). Of the 92 patients, 80 (87%) had complete resections with negative margins (3 had positive margins and 3 had distant metastases discovered at surgery). The pathologic complete response rate was 33% (30 of 92). The median follow-up was 63.5 months. The median survival and disease-specific survival for all enrolled patients was 35 and 59 months, respectively. The 5-year survival and disease-specific survival rate was 40% and 49%, respectively. Patients with a pathologic complete response had a 67% survival rate at 5 years (median not reached), and the remainder of patients had a 5-year survival rate of 27% (median 21 months; p <0.001). For 21 patients alive after 5 years (60-121 months), 2 died of their disease and all others were disease free. Eight patients with pathologic Stage I tumor at the time of surgery had survival similar to those with a complete response to preoperative therapy. The median survival for patients with pathologic Stage IIA, IIB, III, and IV disease at the time of surgery was 22, 13.5, 18, and 4.9 months, respectively. The pattern of initial failure was local/regional alone in 6% (5 of 90), local/regional plus distant in 3% (3 of 90), and distant alone in 47% (42 of 90). No differences were noted in survival or response rate between those with adenocarcinoma or squamous cell carcinoma. CONCLUSION: The promising 5-year survival results and low rate of late cancer-related deaths suggest that these regimens of intensive neoadjuvant therapy may improve the overall cure rate. The pathologic stage after neoadjuvant therapy is an important predictor of survival and may be useful in selecting patients for novel adjuvant therapies. Isolated local failure is uncommon, indicating that efforts to improve the therapeutic outcome should focus on optimizing systemic therapy rather than intensifying the RT. Additional randomized data are needed to assess the benefits of this therapeutic approach fully.     

A three-step strategy of induction chemotherapy then chemoradiation followed by surgery in patients with potentially resectable carcinoma of the esophagus or gastroesophageal junction

BACKGROUND: Patients with locoregional carcinoma of the esophagus or gastroesophageal junction have a poor survival rate after surgery. Preoperative chemotherapy or chemoradiotherapy has not improved the outcome for these patients. Our study was designed to assess the feasibility of preoperative induction combination chemotherapy in addition to chemoradiotherapy to improve the curative resection rate, local control, and survival. PATIENTS AND METHODS Patients having histologic proof of localized carcinoma (either squamous cell carcinoma or adenocarcinoma) of the esophagus or gastroesophageal junction underwent full classification including endoscopic ultrasonography (EUS). Patients first received up to two courses of induction chemotherapy consisting of 5-fluorouracil at 750 mg/m(2)/day as continuous infusion on Days 1--5, cisplatin at 15 mg/m(2)/day as an intravenous bolus on Days 1--5, and paclitaxel at 200 mg/m(2) as a 24-hour intravenous infusion on Day 1. The second course was repeated on Day 29. This was followed by radiotherapy (45 grays in 25 fractions) and concurrent admission of 5-fluorouracil (300 mg/m(2)/day as a continuous infusion 5 days/week) and cisplatin (20 mg/m(2) on Days 1--5 of radiotherapy). After chemoradiotherapy, patients underwent surgery. The feasibility of this approach, curative resection rates, patient survival, and patterns of failure were assessed. RESULTS: Thirty-seven of 38 patients enrolled were evaluable for toxicity and survival. Adenocarcinoma and distal esophageal location of carcinoma were observed frequently. Thirty-five (95%) of the 37 patients underwent surgery, all of whom had an R0 (curative) resection. A pathologic complete response was noted in 11 (30%) of the 37 total patients. In addition, 5 patients (14%) had only microscopic carcinoma. According to EUS classification, 31 (89%) of the 35 patients who underwent surgery had a T3 carcinoma whereas according to pathologic classification only 3 (9%) had a T3 carcinoma (P 相似文献   

中晚期食管癌98例同步放化疗的疗效观察

目的探讨同期放化疗对中晚期食管癌的疗效。方法 98例食管癌中43例行单纯放射治疗（单放组）,以6 MVX常规照射,2 Gy/次,5次/周,照射总剂量为50 Gy,另55例行化放疗联合治疗（化放组）,予顺铂（DDP）联合氟尿嘧啶（5-Fu）（DDP 20 mg/m2,d1～d5;5-Fu 500 mg/m2,d1～d5）,28天为1个周期,放疗方案同单放组,观察两组的近期疗效、远期疗效和不良反应。结果化放组有效率（RR）为65.4%,高于单放组（44.1%）（P〈0.05）。KPS评分化放组较单放组显著提高（P〈0.05）,化放组3年生存率为11.9%,高于单放组（6.9%）（P〈0.05）。两组主要不良反应包括白细胞减少、消化道反应和放射性食管炎,化放组白细胞减少发生率高于单放组（P〈0.05）。结论对中晚期食管癌患者,同期放化疗较单纯放疗的近期疗效更好,可明显改善患者的生存质量,延长患者生存时间,且相对安全。     

Multimodality therapy in advanced paranasal sinus carcinoma: superior long-term results.

PURPOSE: This study was conducted to determine the efficacy of multimodality treatment for stage III and IV, locoregionally advanced paranasal sinus carcinoma. PATIENTS AND METHODS: A subgroup analysis of 19 consecutive patients with stage III or IV paranasal sinus carcinoma treated with multimodality therapy from head and neck cancer protocols between 1984 and 1996 were analyzed for outcome. Sixteen patients received induction chemotherapy consisting of three cycles of cisplatin and 5-fluorouracil, followed by traditional resection (14 patients) or surgical debulking (two patients). Surgery was followed by concomitant chemoradiotherapy with hydroxyurea and 5-fluorouracil in a week-on, week-off sequence in 15 patients. One patient received standard radiation therapy. An additional three patients were treated with a sequence of surgical resection followed by concomitant chemoradiotherapy. The median total dose to the primary tumor was 60 Gy (range, 45-74 Gy). RESULTS: The overall survival at 5 and 10 years by lifetable analysis was 72.7% and 53.9%, respectively, and the disease-free survival at both 5 and 10 years was 66.6%. Local control was 76.1% at both 5 and 10 years. In the subgroup of patients treated with induction chemotherapy, 87% (14/16) achieved a clinical response. A complete response was confirmed at the time of surgery in five patients, whereas 11 patients had residual disease in the surgical specimen. Regional and distant failures were unusual (one patient each), with a 10-year regional control rate of 93% and a distant control rate of 95.5%. Serious, nonreversible long-term complications included two cases of unilateral blindness, one cataract, and one case of ototoxicity. DISCUSSION: An excellent long-term outcome with respect to local control, overall survival, and disease-free survival is achieved in locoregionally advanced paranasal sinus cancer treated with induction chemotherapy, surgery, and concomitant chemoradiotherapy. The 15 patients treated with this regimen had 10-year overall survival, disease-free survival, and local control rates of 56%, 73%, and 79%, respectively. These results are encouraging and are superior to the 40% survival achieved with surgery and radiation therapy. Further investigation of this regimen is warranted.     

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.     

A prospective randomized study of gemcitabine with doxifluridine versus paclitaxel with doxifluridine in concurrent chemoradiotherapy for locally advanced pancreatic cancer

PURPOSE: The objective of this study was to compare the efficacy and toxicity of gemcitabine-based concurrent chemoradiotherapy (CCRT) with paclitaxel-based CCRT in patients with locally advanced pancreatic cancer. METHODS AND MATERIALS: A total of 48 patients who had received no prior therapy were enrolled. The patients were treated with 4500 cGy radiation in 25 fractions over 5 weeks concomitant with gemcitabine 1000 mg/m(2)/week/intravenously (IV) and doxifluridine 600 mg/m(2)/day/by mouth (PO), or paclitaxel 50 mg/m(2)/week/IV and doxifluridine 600 mg/m(2)/day/PO. After a 4-week rest, the responses were evaluated and maintenance therapies (operation or chemotherapy) (gemcitabine 1000 mg/m(2)/week/IV and doxifluridine 600 mg/m(2)/day/PO) were conducted. RESULTS: The median survival was 12 months in the gemcitabine group vs. 14 months in the paclitaxel group. The response rate was 13.6% vs. 25%, and the median time to progression was 12 months vs. 12.5 months, respectively. The positive rate of the clinical benefit response was 59.1% vs. 41.7%, respectively. Toxicities were acceptable in both groups. CONCLUSION: In this trial, we demonstrated that the gemcitabine-based CCRT and the paclitaxel-based CCRT in combination of doxifluridine are clearly acceptable treatment strategy, and appear more effective than the 5 fluorouracil-based CCRT for locally advanced pancreatic cancer with comparable tolerability. Furthermore, the paclitaxel-based CCRT showed similar efficacy and toxicities to the gemcitabine-based treatment when it was combined with 5-fluorouracil.     

Preoperative hyperfractionated radiotherapy with concurrent chemotherapy in resectable esophageal cancer

PURPOSE: To evaluate the local control rates, survival rates, and patterns of failure for esophageal cancer patients receiving preoperative concurrent chemotherapy and hyperfractionated radiotherapy followed by esophagectomy. METHODS AND MATERIALS: From May 1993 through January 1997, 94 patients with resectable esophageal cancers received continuous hyperfractionated radiation (4,800 cGy/40 fx/4 weeks), with concurrent FP chemotherapy (5-FU 1 g/m(2)/day, days 2-6, 30-34, CDDP 60 mg/m(2)/day, days 1, 29) followed by esophagectomy 3-4 weeks later. If there was evidence of disease progression on preoperative re-evaluation work-up, or if the patient refused surgery, definitive chemoradiotherapy was delivered. Minimum follow-up time was 2 years. RESULTS; All patients successfully completed preoperative treatment and were then followed until death. Fifty-three patients received surgical resection, and another 30 were treated with definitive chemoradiotherapy. Eleven patients did not receive further treatment. Among 91 patients who received clinical reevaluation, we observed 35 having clinical complete response (CR) (38.5%). Pathologic CR rate was 49% (26 patients). Overall survival rate was 59.8% at 2 years and 40.3% at 5 years. Median survival time was 32 months. In 83 patients who were treated with surgery or definitive chemoradiotherapy, the esophagectomy group showed significantly higher survival, disease-free survival, and local disease-free survival rates than those in the definitive chemoradiation group. CONCLUSION: Preoperative chemoradiotherapy in this trial showed improved clinical and pathologic tumor response and survival when compared to historical results. Patients who underwent esophagectomy following chemoradiation showed decreased local recurrence and improved survival and disease-free survival rates compared to the definitive chemoradiation group.     

新辅助放化疗联合手术与单纯手术治疗局部晚期食管癌的疗效比较

目的探讨新辅助放化疗联合手术治疗局部晚期食管癌较单纯手术治疗能否改善总生存率。方法Ⅱa～Ⅲ期食管癌患者60例,随机分成新辅助放化疗联合手术组及单纯手术治疗组,每组30例。化疗使用PF方案,DDP 75 mg/（m2.d）,d1,5-FU 500 mg/（m2.d）,d1-5持续滴注,第1次化疗与第1次放疗同时实施,每3周1个疗程,放疗期间共2个疗程。放化疗结束后2-4周行食管癌根治术。放疗剂量PTV靶区给予每次2.0 Gy,5次/周,总剂量50 Gy。结果给予新辅助放化疗联合手术组患者必要的对症支持治疗,患者均能够完成同期放化疗。新辅助放化疗联合手术组并发症多于单纯手术组,但两组比较差异无统计学意义。1、2、3年生存率新辅助放化疗联合手术组分别为83.3%、65.3%、42.8%,单纯手术组分别为80.0%、41.6%、25.0%（χ2=3.992,P=0.046）。结论新辅助放化疗联合手术治疗可以改善局部晚期食管癌的总生存率,且不明显增加术后并发症,值得临床推广应用。     

同步放化疗与序贯放化疗治疗中晚期食管癌的临床研究

目的 比较同步放化疗与序贯放化疗治疗中晚期食管癌的近期疗效和长期生存率.方法 168例中晚期食管癌患者随机分为两组:同步放化疗组91例;序贯放化疗组77例.同步放化疗组:放疗2 Gy/次,总量50～ 56 Gy.同步化疗2周期,放疗结束后继续化疗4周期;序贯放化疗组:放疗2 Gy/次,总量60 ～64 Gy.待放疗结...     

TPF诱导化疗或PF诱导化疗联合同期放化疗治疗局部晚期鼻咽癌的临床观察

背景与目的：TPF(多西他赛+顺铂+氟尿嘧啶)诱导化疗加同期放化疗治疗局部晚期鼻咽癌的疗效尚不清楚。该研究旨在比较TPF诱导化疗或PF(顺铂+氟尿嘧啶)诱导化疗联合同期放化疗治疗局部晚期鼻咽癌的疗效和耐受性。方法：将局部晚期鼻咽癌患者随机分为两组。TPF组116例接受TPF诱导化疗(多西他赛60 mg/m2,第1天+顺铂60 mg/m2,第1天+氟尿嘧啶750 mg/m2,持续静脉滴注120 h),每3周重复,共3个疗程。PF组116例接受PF诱导化疗(顺铂80 mg/m2,第1天+氟尿嘧啶750 mg/m2,持续静脉滴注120 h),每3周重复,共3个疗程。诱导化疗结束后行同期放化疗,放疗采用调强适形放疗(intensity modulated radiation therapy,IMRT)技术,大体肿瘤靶区(gross tumor volume,GTV)6810 cGy/30次,5次/周,共6周,同期化疗用顺铂80 mg/m2,第1、22天。评价完全缓解(complete response,CR)、部分缓解(partial response,PR)和有效缓解率(response rate,RR), RR=CR+PR。评价两组患者的近期疗效及不良反应,并随访比较5年无进展生存(progression-free survival,PFS)和5年总生存(overall survival,OS)。结果：诱导化疗结束后和治疗结束后13周TPF组的有效缓解率都高于PF组,两组差异有统计学意义(P=0.001,P=0.002);TPF组中位复发时间为2.98年,5年的PFS为84.48%,PF组中位复发时间为2.32年,5年的PFS为82.75%,差异无统计学意义(P=0.458);TPF组5年的OS为87.06%,PF组5年的OS为85.34%,差异无统计学意义(P=0.274)。TPF组在中性粒细胞下降、血小板下降、肝功能和肾功能损伤、腹泻以及黏膜坏死的发生上均明显高于PF组,差异有统计学意义(P<0.001),TPF组发生Ⅲ度和Ⅳ度不良反应较PF组明显增高,差异有统计学意义(P<0.001)。结论：TPF方案诱导化疗治疗局部晚期鼻咽癌的临床疗效并不优于PF方案诱导化疗治疗局部晚期鼻咽癌,且TPF方案诱导化疗的不良反应较PF方案明显,临床上不适合推广。     

Gastroesophageal junction adenocarcinoma

Opinion statement The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing in association with the epidemiologic rise in distal esophageal adenocarcinoma and gastric cardial (AEG type III) tumors [1-4]. The overall survival rate is poor in most patients with AEG because lymph node or visceral metastases are frequently present at the time patients become symptomatic [5]. A few patients are identified early in the disease because of screening for gastroesophageal reflux and Barrett's esophagus [6,7]. Early stage AEG (T1N0 or T2NO, carcinoma in situ, or severe dysplasia [50% risk of developing adenocarcinoma in 5 years]) can in many instances be cured with surgery alone. Ablative treatments for early stage AEG, including endoscopic fulguration by cautery and laser or photodynamic therapy, are investigational at this time [8]. Locoregionally advanced AEG (T3, T4, N1, or M1a [nonregional lymph nodes]) without distant systemic metastases (M1b) has a poor overall survival rate with surgery alone or definitive chemotherapy and radiation therapy without surgery [9,10,11]. Analysis of the use of multimodality treatment strategies for locoregionally advanced AEG types I and II have demonstrated improved survival rates in two small phase III trials with preoperative concurrent chemoradiotherapy followed by surgical resection [12,13]. In contrast, three small phase III trials with preoperative concurrent or sequential chemoradiotherapy in patients with predominantly squamous cell carcinoma did not demonstrate any clear survival advantage [14-16]. Additionally, a randomized phase III study evaluating preoperative chemotherapy without radiation therapy in esophageal cancer (predominantly adenocarcinoma) has demonstrated no survival benefit [10]. In light of these results, additional large randomized phase III studies are needed to confirm the potential benefit of preoperative concurrent chemoradiotherapy. At the present time, preoperative chemoradiotherapy remains investigational. For locoregionally advanced gastric adenocarcinoma, including AEG type III, postoperative concurrent 5-fluorouracil (5-FU)-based chemoradiotherapy is associated with improved survival as demonstrated in a recently completed random assignment trial (INT 0116) [17,18]. As a result, surgery with postoperative chemoradiotherapy has recently become the standard of care for patients with AJCC stage II and III gastric adenocarcinoma (including patients with AEG type III). Metastatic AEG (M1b) should be treated with palliative chemotherapy (in good performance patients) or supportive care (poor performance) in asymptomatic patients. Radiation therapy and endoscopic stent placement (expandable wire mesh) can be used to palliate dysphagia in patients with M1b disease. The development of expandable stents and improved radiotherapy has obviated surgical bypass to palliate patients with symptomatic, metastatic AEG.     

Paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation in locally advanced nasopharyngeal carcinoma.

BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced nasopharyngeal carcinoma (NPC). We conducted a phase II trial using paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation (TFHX). PATIENTS AND METHODS: Fifty-nine patients with locally advanced NPC were treated with CRT consisting of 4-day continuous infusions of paclitaxel (20 mg/m(2)/d) and 5-fluorouracil (600 mg/m(2)/d), and oral hydroxyurea 500 mg bid for nine doses, every 3 weeks concurrent with radiotherapy (RT). RT consisted of once daily 200cGy fractions 5 times per week to a total of 7000cGy. RESULTS: Complete response was seen in 86% and 71% of patients at 4 and 12 months after CRT. The median follow-up was 34 months. Twenty-three patients experienced relapse. Sixteen deaths occurred: 13 from progressive disease. Three-year overall survival and progression-free survival were 72% and 54% respectively, with locoregional and distant control rates of 83% and 64% at 3 years respectively. Grade 3 to 4 acute toxicities included oropharyngeal mucositis in 81% of patients treated, dermatitis in 63%, weight loss in 32%, and neutropenia in 22%. Neutropenic fever was seen in 14%. There were no treatment-related deaths from acute toxicity. CONCLUSIONS: TFHX is shown to be feasible in NPC. Non-cross resistant induction chemotherapy should be further studied with this regimen.     

紫杉醇脂质体联合5-FU/DDP治疗晚期食管癌49例临床观察

目的观察紫杉醇脂质体联合5-FU/DDP治疗晚期食管癌的疗效及不良反应。方法 49例患者使用紫杉醇脂质体135 mg/m2,5-FU 500 mg/m2静脉滴注,第1-5天;顺铂25 mg/m2静脉滴注,第1-3天。21天为1周期,连用2周期后按照实体瘤疗效评价标准(RECIST 1.0)评价疗效。结果 49例患者共完成212周期化疗,平均完成4.3周期,CR 4例(8.2%),PR 19例(38.8%),SD 12例(24.4%),PD 14例(28.6%),总有效率(CR+PR)47.0%,临床受益率(CR+PR+SD)74.4%。中位疾病进展时间6月(95%CI:5.09～6.91)。49例患者1年生存率为79.6%(39/49),2年生存率为46.9%(23/49)。不良反应主要为血液学毒性及消化道反应。结论紫杉醇脂质体联合5-FU/DDP治疗晚期食管癌具有较好的有效性及安全性。     

Sequential administration of methotrexate, cisplatin, and 5-fluorouracil in multimodal therapy for locally advanced head and neck cancer

Thirty-eight previously untreated patients with locally advanced head and neck cancer received three cycles of induction chemotherapy with methotrexate (120 mg/m2) followed by cisplatin (100 mg/m2) and a 5-day continuous infusion of 5-fluorouracil (1,000 mg/m2 per day). The response rate in 34 evaluable patients was 94%, with a complete response rate of 26%. Thirty-one patients underwent local therapy following induction chemotherapy, and 25 (81%) were rendered free of disease: 14 of 15 treated with surgery and radiotherapy and 11 of 16 treated with radiotherapy alone. At a median follow-up of 11 months, 8 patients have relapsed while the remaining 17 patients continue free of disease. The dose-limiting toxicity of chemotherapy was mucositis resulting in reduction of the 5-fluorouracil dose in 28 patients. This regimen is highly effective in inducing responses in patients with locally advanced head and neck cancer; 81% of the patients who complete local therapy are rendered free of disease with this multimodal approach. Due to short follow-up, the relapse rate, overall survival, and disease-free survival cannot yet be determined.     

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。     

Radiochemotherapy with short daily infusion of low-dose oxaliplatin,leucovorin, and 5-FU in T3-T4 unresectable rectal cancer: a phase II IATTGI study

PURPOSE: Oxaliplatin (OXA)/5-fluorouracil (5-FU) have confirmed their preclinical synergy in advanced colorectal cancer patients. Chemoradiotherapy with 5-FU + leucovorin (LV) is considered the standard treatment in unresectable rectal cancer patients. The objective was to evaluate OXA with 5-FU + LV and concurrent radiotherapy in unresectable rectal cancer patients. PATIENTS AND METHODS: Treatment: OXA 25 mg/m(2)/day in 30-min infusions, followed by bolus LV 20 mg/m(2)/day and bolus 5-FU 375 mg/m(2)/day. All drugs were given on 4 days during Weeks 1 and 5 of a standard radiotherapy cycle (50.4 Gy). A single OXA dose (50 mg/m(2)) was also given on the third week of radiotherapy. A cycle of OXA with 5-FU + LV was administered 4 weeks after chemoradiotherapy, with surgery planned 4 weeks later. RESULTS: Between March 1998 and April 2000, 22 patients with T3-T4 unresectable rectal cancer were accrued. Patient characteristics included the following: 11 females, 11 males, median age 58 (range: 18-76). Performance status ECOG (PS) 0: 2 patients, PS 1: 7 patients, and PS 2: 13 patients. The following RTOG Grade 3-4 toxicities were reported: diarrhea, 6 patients; cutaneous, 3 patients; neutropenia-leukopenia, 2 patients; and thrombocytopenia, 1 patient; 1 treatment-related death resulted (febrile neutropenia-sepsis after chemoradiotherapy). Only 1 patient had neurosensory Grade 2 (OXA-specific Levi's scale) toxicity. Nine patients had PS worsening during treatment. Five patients had chemoradiotherapy delay (median: 6 days). Of 22 patients, 16 underwent surgery (without serious surgical complications); 12/16 had a complete resection (5/12 had sphincter preservation). Pathologic examination revealed 3/12 complete remissions, 2/12 minimal microscopic residual disease, 2/12 T2N0, 1/12 T3N0, and 4/12 positive nodes; 4/16 had unresectable disease. Median follow-up was 15 months (range: 3.0-43.4 months), median time to progression was 15.7 months (CI 95%, 0, 31.7), and median overall survival was 19.5 months (CI 95%, 18.0, 21). CONCLUSIONS: Outpatient treatment with low-dose, 30-min daily OXA infusion was feasible and very active, with acceptable toxicity.     

Postoperative chemoradiotherapy in gastric cancer: a phase I study of radiotherapy with dose escalation of oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX regimen)

Concurrent chemoradiotherapy begins to be more and more widely accepted as a standard adjuvant treatment in gastric cancer. And oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) also reveals to be a very effective regimen in gastric cancer. But the safety and the dosages of FOLFOX combining with radiotherapy are still unknown. This study was to determine the maximum-tolerated dose and the dose-limiting toxicity of FOLFOX with higher-dose concurrent radiotherapy (RT) as adjuvant treatment in patients with gastric cancer. Patients with Stage II/III gastric cancer after surgery were recruited. They received one cycle of induction chemotherapy (standard FOLFOX4). Then, they received 50.4 Gy in 1.8-Gy fractions in combination with two cycles of concurrent FOLFOX, and oxaliplatin among this regimen was administered with escalating doses. Dose-limiting toxicity including grade 3 or grade 4 hematologic and nonhematologic toxicities was investigated. Fifteen patients were enrolled at the following dose levels: oxaliplatin 55 mg/m(2) (3 patients), 65 mg/m(2) (6 patients), and 75 mg/m(2) (6 patients). Dose-limiting toxicity was observed in 1 patient at 65 mg/m(2) (grade 4 leukopenia) and in 3 patients at 75 mg/m(2) (1 patient had grade 4 leukopenia, 1 had grade 3 thrombocytopenia, and 1 had grade 3 stomatitis). Combination chemotherapy FOLFOX with oxaliplatin 65 mg/m(2), d 1; leucovorin 200 mg/m(2), 2 h, d1-2; 5-fluorouracil 400 mg/m(2), iv, d 1-2 and 600 mg/m(2) civ, 22 h, d 1-2 given concurrently with RT (50.4 Gy) can be recommended as a safer and preferable regimen for the adjuvant treatment of patients with gastric cancer.     

Cisplatin, fluorouracil, and leucovorin induction chemotherapy followed by concurrent cisplatin chemoradiotherapy for organ preservation and cure in patients with advanced head and neck cancer: long-term follow-up.

PURPOSE: The poor functional outcome in patients with advanced head and neck squamous cell carcinoma (HNSCC) with surgery and radiation has led to alternative approaches to advanced disease. We conducted a phase II study of induction chemotherapy followed by concurrent chemoradiotherapy for organ preservation in patients with advanced resectable and unresectable (nasopharyngeal) tumors. PATIENTS AND METHODS: Forty-two patients with stage III to IV resectable HNSCC and nasopharyngeal tumors received induction chemotherapy with two courses of cisplatin (20 mg/m2/d continuous infusion [CI]), fluorouracil (800 mg/m2/d CI), and leucovorin (500 mg/m2/d CI; PFL) for 4 days followed by concurrent therapy with cisplatin (100 mg/m2/d on days 1 and 22) and approximately 70 Gy of external-beam radiotherapy. RESULTS: Response to induction chemotherapy included partial response rate of 52% and complete response rate of 24%. The most common grade 3 or 4 toxicity was neutropenia (59%). After cisplatin chemoradiotherapy the complete response rate was 67%. Toxicities of cisplatin chemoradiotherapy consisted of grade 3 or 4 mucositis (79%) and neutropenia (51%). At a median follow-up of 71.5 months, 43% of the patients are still alive and disease-free. The 5-year progression-free survival (PFS) rate was 60%, and the 2- and 5-year overall survival (OS) rates were 67% and 52%, respectively. Three patients died of second primaries. Late complications of treatment included xerostomia and hoarseness. One patient had persistent dysphagia and required laser epiglotectomy 108 months after treatment. CONCLUSION: Induction chemotherapy with PFL followed by concurrent cisplatin chemoradiotherapy is well tolerated and results in a good likelihood of organ preservation and excellent PFS and OS.