TP诱导联合DDP同期放化疗治疗局部晚期食管癌临床研究

  目的  研究不适手术的局部晚期食管癌患者行TP方案诱导化疗联合DDP同期放化疗的毒性及疗效。  方法  33例胸段食管鳞癌T₃N₀M_O~T₄N₂M₀期患者（不包括腹腔淋巴结转移）,第1天和第22天行TP方案诱导化疗,多西他赛（艾素）75 mg/m2, DDP 75 mg/m2。第43天开始放疗,采用三维适形放疗,总剂量60 Gy,2 Gy/次,5次/周。同期化疗:DDP 30 mg/m2,1次/周,放疗开始的第1、8、15、22、29、36天给药。  结果  诱导化疗Ⅳ级骨髓毒性为12.12%（4/33）,无Ⅲ级或以上的肝、肾毒性。同期放化疗骨髓毒性最高为Ⅲ级,红细胞、粒细胞、血小板Ⅲ级毒性分别为21.21%（7/33）、15.15%（5/33）、3.03%（1/33）,无Ⅱ级以上的肝肾毒性。Ⅲ级放射性食管炎为9.10%（3/33）,未发现Ⅲ级以上的放射性食管炎及Ⅰ级以上的急性放射性肺炎。治疗结束评价显效（CR+PR）84.85%（28/33）,稳定（SD）12.12%（4/33）,进展（PD）3.03%（1/33）;治疗后2个月评价显效（CR+PR）75.76%（25/33）,稳定（SD）9.10%（3/33）,进展（PD）15.15%（5/33）。全组死亡病例15例。1年生存率66.4%,最主要失败模式是局部失败46.67%（7/15）,局部+远处失败26.67%（4/15）。  结论  局部晚期食管癌患者行TP方案诱导化疗+DDP同期放化疗的毒性可以耐受,局部失败仍然是主要的失败模式。      

Phase I trial of escalating-dose irinotecan given weekly with cisplatin and concurrent radiotherapy in locally advanced esophageal cancer.

PURPOSE: To identify the maximum-tolerated dose and dose-limiting toxicity (DLT) of weekly irinotecan combined with cisplatin and radiation in esophageal cancer. PATIENTS AND METHODS: Nineteen patients with clinical stage II to III esophageal squamous cell or adenocarcinoma were treated on this phase I trial. Induction chemotherapy with weekly cisplatin 30 mg/m2 and irinotecan 65 mg/m2 was administered for four treatments during weeks 1 to 5. Radiotherapy was delivered weeks 8 to 13 in 1.8-Gy daily fractions to a dose of 50.4 Gy. Cisplatin 30 mg/m2 and escalating-dose irinotecan (40, 50, 65, and 80 mg/m2) were administered on days 1, 8, 22, and 29 of radiotherapy. DLT was defined as a 2-week delay in radiotherapy for grade 3 to 4 toxicity. RESULTS: Minimal toxicity was observed during chemoradiotherapy, with no grade 3 or 4 esophagitis, diarrhea, or stomatitis. DLT caused by myelosuppression was seen in two of six patients treated at the 80-mg/m2 dose level, thus irinotecan 65 mg/m2 was defined as the recommended phase II dose. Dysphagia improved or resolved after induction chemotherapy in 13 (81%) of 16 patients who reported dysphagia before therapy. Only one patient (5%) required a feeding tube. Six complete responses (32%) were observed, including four pathologic complete responses in 15 patients selected to undergo surgery (27%). CONCLUSION: Cisplatin, irinotecan, and concurrent radiotherapy can be administered on a convenient schedule with relatively minimal toxicity and an acceptable rate of complete response in esophageal cancer. Further phase II evaluation of this regimen is ongoing. A phase III comparison to fluorouracil or taxane-containing chemoradiotherapy should be considered.     

Preoperative concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced non-small-cell lung cancer

The objective of this study was to assess the feasibility and effectiveness of an induction chemoradiotherapy regimen followed by surgery in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). A total of 22 patients with LA-NSCLC were treated with induction chemoradiotherapy consisting of cisplatin (40 mg m(-2)) and docetaxel (40 mg m(-2)) given on days 1, 8, 29 and 36 plus concurrent thoracic irradiation at a dose of 40-60 Gy (2 Gy fraction(-1) day(-1)). Surgical resection was performed within 6 weeks after completion of induction therapy. Objective response to the induction therapy was obtained in 16 patients (73%). In all, 20 patients (91%) underwent surgery and complete resection was achieved in 19 patients (86%). Pathological downstaging and pathological complete response were obtained in 14 (64%) and five (23%) patients, respectively. With a median follow-up period of 32 months, the calculated 3-year overall and progression-free survival rates were 66 and 61%, respectively. It is noteworthy that the 3-year overall survival rate in 14 patients achieving pathological downstaging was extremely high (93%). Toxicity was manageable with standard approaches. No treatment-related deaths occurred. This combined modality treatment is feasible and highly effective in patients with LA-NSCLC. The results warrant further large-scale study to confirm the effectiveness of this regimen.     

Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer

Background:

Locally advanced oesophageal cancer (LAEC) is associated with poor survival and more effective treatments are needed. The aim of this phase I trial was to assess the maximum tolerated dose (MTD) of a novel weekly docetaxel and cisplatin regimen concurrent with radical radiotherapy.

Methods:

Patients with unresectable, non-metastatic LAEC were eligible. Treatment comprised docetaxel 15–30 mg m⁻² per week and cisplatin 15–30 mg m⁻² per week in six planned dose levels (DLs) in 3–6 patient cohorts with 50 Gy radiotherapy in 25 fractions. Maximum tolerated dose was based on defined dose-limiting toxicities (DLTs) during therapy and 2 weeks post therapy.

Results:

A total of 24 patients were enrolled. There were two DLTs: grade 3 fever in DL1 (docetaxel 15 mg m⁻², cisplatin 15 mg m⁻²) and grade 3 nausea in DL2 (20 mg m⁻², 15 mg m⁻²). These DLs were each expanded to six patients without further DLTs. The most common acute toxicity was grade 3 radiation oesophagitis (37.5%). There were no grade 4 toxicities, and haematologic toxicity was minimal. Cisplatin and docetaxel dose intensity was 100% at the highest dose level (DL6). A MTD was not reached in this trial. Tumour overall response rate was 50% (33% complete, 17% partial).

Conclusion:

Cisplatin and docetaxel each 30 mg m⁻² per week concurrent with 50 Gy radiotherapy is recommended for use in phase II clinical trials in oesophageal cancer.     

Phase II study of weekly docetaxel combined with cisplatin in patients with advanced non-small-cell lung cancer

Purpose To evaluate the safety and efficacy of the combination of cisplatin on day 1 and docetaxel on days 1, 8 and 15 every 4 weeks for the treatment of previously untreated patients with non-small-cell lung cancer (NSCLC).Patients and methods A group of 38 patients with advanced or metastatic NSCLC who had not received prior treatment and who were aged under 75 years were enrolled. The patients received intravenous infusions of docetaxel (25 mg/m², days 1, 8, 15) and cisplatin (80 mg/m², day 1), followed by a week of rest.Results Six patients had grade 3/4 neutropenia (18%), but there were no episodes of neutropenic fever. Nonhematologic toxicities were also mild. There were 12 partial responses for an objective response rate of 31.6%. The median survival was 11.8 months, and the 1-year survival rate was 46.5%.Conclusion Cisplatin combined with weekly administration of docetaxel is efficacious against NSCLC with low hematotoxicity, and this schedule may be an alternative for the treatment of NSCLC.     

Phase I trial of weekly docetaxel combined with cisplatin in patients with non-small cell lung cancer

The phase I study was conducted to evaluate the maximum tolerated dose (MTD) and toxicity of weekly administered docetaxel combined with cisplatin in patients with non-small-cell lung cancer (NSCLC). In a dose escalation study, 22 patients, under 75 years old, with unresectable and metastatic untreated NSCLC with performance status (0-1) were enrolled. Patients were treated with cisplatin (day 1) and weekly docetaxel (days 1, 8, 15). Dose escalation levels in mg/m(2) were for cisplatin and docetaxel; 70 and 15 (level 1), 80 and 15 (level 2), 80 and 20 (level 3), 80 and 25 (level 4), 80 and 30 (level 5), respectively. Chemotherapy was repeated for at least two cycles every 28 days. All patients were assessable for toxicities. Although grade 3 neutropenia occurred in one case in level 4, there were no significant modifications of chemotherapy schedule until level 4. Grade 3 neutropenia occurred in all cases receiving level 5. One patient developed an infection, and two had incomplete recovery of neutropenia by the 28th day after the first cycle of chemotherapy. Nonhematological toxicities, including nephrotoxicity, nausea/vomiting, alopecia and hypersensitivity reaction, were tolerable. However, one case developed severe hyponatremia. Among 21 patients evaluable for response, eight cases achieved partial response, thus the overall response was 39%. Weekly administration of docetaxel at 25 mg/m(2) (days 1, 8, 15) combined with cisplatin 80 mg/m(2) (day 1) is recommended for phase II studies. The responses observed in the present study suggest an identical high degree of activity against NSCLC with less hematotoxicity compared with a standard schedule of cisplatin and docetaxel.     

A phase II study of concurrent chemoradiotherapy with weekly docetaxel and cisplatin in advanced oesophageal cancer

Background

Concurrent chemoradiotherapy (CRT) is a main treatment option for patients with advanced oesophageal cancer. However, improvement of survival outcomes and toxicities according to the selected treatment is still needed. This phase II trial was conducted to assess the efficacy and safety of concurrent CRT with weekly docetaxel and cisplatin in advanced oesophageal cancer.

Methods

Patients with unresectable oesophageal cancer due to advanced stage or patients medically unfit for surgery were enrolled. Patients received 20?mg/m² docetaxel and 25?mg/m² cisplatin in weeks 1, 2, 3, 5, 6, and 7 with concurrent 54-Gy radiotherapy at 200?cGy/day.

Results

Thirty-six patients with oesophageal squamous cell carcinoma were enrolled from December 2007 to December 2009. Among them, the toxicity and response rate of 35 were evaluated. Thirty-five patients completed radiotherapy as planned, and 33 completed chemotherapy as planned. Grade 3 or 4 toxicity during CRT included leucopenia (5.7?%), febrile neutropenia (2.9?%), oesophagitis (22.9?%), and tracheo-oesophageal fistula (5.7?%). After CRT, 8 patients (22.9?%) had a complete response, 22 (62.9?%) had a partial response, 4 (11.4?%) had stable disease, and 1 (2.9?%) had progressive disease. Improvement of dysphagia was observed in 85.3?%. At a median follow-up of 26.7?months, the median time to progression was 13.5?months, and median overall survival was 26.9?months. The 3-year progression-free survival rate was 16.7?%, and survival rate was 27.8?%.

Conclusion

Concurrent CRT with weekly docetaxel and cisplatin was well tolerated and is a convenient combination with promising efficacy. This result indicated favourable activity in terms of both tumour and symptom control.     

A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer

This study investigated the maximum-tolerated dose of gemcitabine based on the frequency of dose-limiting toxicities of weekly gemcitabine treatment with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Fifteen patients with locally advanced pancreatic cancer that was histologically confirmed as adenocarcinoma were enrolled in this phase I trial of weekly gemcitabine (150-350 mg x m(-2)) with concurrent radiotherapy (50.4 Gy in 28 fractions). Gemcitabine was administered weekly as an intravenous 30-min infusion before radiotherapy for 6 weeks. Three of six patients at the dose of 350 mg x m(-2) of gemicitabine demonstrated dose-limiting toxicities involving neutropenia/ leukocytopenia and elevated transaminase, while nine patients at doses of 150 mg x m(-2) and 250 mg x m(-2) did not demonstrate any sign of dose-limiting toxicity. Of all 15 enrolled patients, six patients (40.0%) showed a partial response. More than 50% reduction of serum carbohydrate antigen 19-9 level was observed in 13 (92.9%) of 14 patients who had pretreatment carbohydrate antigen 19-9 levels of 100 U x ml(-1) or greater. The maximum-tolerated dose of weekly gemcitabine with concurrent radiotherapy was 250 mg x m(-2), and this regimen may have substantial antitumour activity for patients with locally advanced pancreatic cancer. A phase II trial of weekly gemcitabine at the dose of 250 mg x m(-2) with concurrent radiation in patients with locally advanced pancreatic cancer is now underway.     

Cisplatin and weekly docetaxel with concurrent thoracic radiotherapy for locally advanced stage III non-small-cell lung cancer

Purpose  Our objective was to assess the efficacy and toxicity of concurrent chemoradiotherapy with cisplatin + weekly divided-dose docetaxel in patients with stage III non-small-cell lung cancer (NSCLC). Methods  A total of 34 patients aged less than 75 years old with locally advanced stage III NSCLC were enrolled. The patients received intravenous infusions of cisplatin (80 mg/m²; day 1) and docetaxel (20 mg/m²; days 1, 8, 15), followed by a week’s drug-free interval. Standard concurrent thoracic radiotherapy was given for 6 weeks (2 Gy per fraction; total dose, 60 Gy). Results  Over Grade 3 neutropenia, esophagitis and pulmonary toxicities were observed in 23.5, 17.6 and 11.8% of the cases, respectively. One complete response and 20 partial responses were obtained, with an objective response rate of 61.8%. The median survival time was 26.4 months (95% CI 16.9—not reached) and the 1- and 3-year survival rates were 76.5 and 41.2%, respectively. Conclusion  Cisplatin + weekly docetaxel with concurrent radiotherapy is a feasible and effective regimen for locally advanced NSCLC.     

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.     

多西他赛联合顺铂和5-氟尿嘧啶治疗晚期复治食管癌的临床疗效

目的探讨多西他赛联合顺铂和5-氟尿嘧啶治疗晚期复治食管癌的临床疗效。方法选取2012年5月至2016年5月间云南省肿瘤医院收治的80例晚期复治食管癌患者,采用等距随机抽样法分为观察组与对照组,每组40例。观察者患者采用多西他赛联合顺铂和5-氟尿嘧啶治疗,对照组患者采用多西他赛联合顺铂治疗,2个疗程后比较临床疗效。结果观察组患者治疗总有效率为62.5%,生活质量总分(88.14士1.21)分,对照组患者总有效率为47.5%,生活质量总分(75.33±1.25)分,两组比较差异均有统计学意义(均P<0.05);对照组患者不良反应发生率为15.0%,观察组患者为17.5%,两组比较差异无统计学意义(P>0.05)。结论多西他赛联合顺铂与5-氟尿嘧啶化疗方案治疗晚期复治食管癌疗效显著,可作为首选治疗方案推广使用。     

Phase I/II study of weekly docetaxel dose escalation in combination with fixed weekly cisplatin and concurrent thoracic radiotherapy in locally advanced non-small cell lung cancer

Purpose: We conducted a phase I study to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly docetaxel and cisplatin (DOC/CDDP) with concurrent thoracic radiotherapy (TRT) in patients with unresectable stage III non-small-cell lung cancer (NSCLC). Materials and methods: The DOC/CDDP administration schedules consisted of a split schedule (SS) with administration in 3 out of every 4 weeks, and a continuous schedule (CS) with administration every week. TRT was given to a total dose of 60 Gy at 2 Gy per fraction over 6 weeks. Results: Twenty-one patients entered the study. The patient characteristics were: PS 0/1/2, 6/13/2; Sq/Ad, 16/5; stage IIIA/IIIB, 4/17. The principal DLT was grade3 esophagitis. The MTD of DOC on the SS and CS in combination with CDDP (25 mg/m2/week) was 25 and 20 mg/m²/week, respectively. We determined the RD and schedule of DOC/CDDP on the SS to be 20/25 mg/m²/week. The serum α-1-acid glycoprotein (AAG) concentration values were found to be negatively correlated with the grade of esophagitis. The median survival time was 23.1 months. Conclusion: The chemoradiation regimen tested in this study has promising activity and manageable toxicity. The continuous schedule could not be recommended due to excessive toxicity. The main DLT was esophagitis, and it significantly correlated with the plasma AAG concentration.Conflicts of interest: The authors indicated no potential conflicts of interest     

中晚期宫颈癌多西他赛联合顺铂化疗同步放疗临床观察

目的探讨多西他赛联合顺铂化疗同步放疗治疗中晚期宫颈癌的临床疗效及不良反应。方法内蒙古医科大学附属人民医院2005-04-15-2009-04-15收治96例ⅡB-ⅢB期宫颈癌患者,其中放化疗50例（给予多西他赛联合顺铂化疗同步放疗）,接受单纯放疗46例。单纯放疗组应用盆腔外照射联合腔内近距离照射放疗方案,外照射采用6 MV X直线加速器,利用三维适形技术,盆腔四野盒式照射,剂量达（24-30）Gy/（12-15）次,腔内近距离照射A点剂量为7Gy/次,共6-7次。放化疗组化疗应用TP方案,3周为1个周期,连续治疗2-3个周期。具体用药为多西他赛75mg/m2,静脉滴入,d1;顺铂75mg/m2,静脉滴入,d1-d3。化疗当天开始行放射治疗,放疗方案与单纯放疗组相同。按照WHO实体瘤疗效判定标准,比较两组患者的近期临床疗效及远期临床效果,并比较不良反应。结果 96例患者均完成了放疗和化疗。放化疗组治疗后,完全缓解率为20.0%,显著高于单纯放疗组的6.5%;总体有效率为62.0%,显著高于单纯放疗组的34.8%,χ2=3.972,P=0.031。放化疗组1年生存率为98.0%,与单纯放疗组的93.5%相比,差异无统计学意义,χ2=7.793,P=0.281;放化疗组2年生存率为86.0%,优于单纯放疗组的63.0%,χ2=10.472,P=0.026;放化疗组局部复发率为8.0%,优于单纯放疗组的30.4%,χ2=13.851,P=0.008;放化疗组远处转移率为10.0%,优于单纯放疗组的36.9%,χ2=11.635,P=0.031。放化疗组胃肠道反应、骨髓抑制、放射性直肠炎和放射性膀胱炎的发生率分别为98.0%、96.0%、52.0%和50.0%,显著高于放疗组的71.7%、76.1%、30.4%和28.3%,但经对症处理后均得以缓解,患者可以耐受,不影响治疗的进程。结论顺铂联合多西他赛同步放疗治疗中晚期宫颈癌,可显著增强治疗效果,能明显提高患者的生存率。     

周剂量多西他赛联合顺铂、5-FU治疗晚期食管癌的临床观察

目的:观察周剂量多西他赛联合顺铂、5-FU治疗晚期食管癌的临床疗效及不良反应。方法:47例晚期食管癌患者,应用多西他赛30mg/m2静脉滴注第1、8、15天,顺铂20mg/m2静脉滴注第1-5天,5-FU500mg/m2静脉滴注第1-5天,每28天重复。治疗2个周期评价疗效,每周期评价毒性。结果:47例患者均可评价疗效。获CR 3例,PR 21例,总有效率(CR+PR)为51.06%。所有患者中位疾病进展时间为149天,中位生存时间274天。主要不良反应为骨髓抑制,出现Ⅲ/Ⅳ度中性粒细胞减少13例(27.7%),Ⅲ度血小板减少3例(6.4%),Ⅲ度贫血5例(10.6%),无治疗相关性死亡。结论:周剂量多西他赛联合顺铂、5-FU治疗晚期食管癌疗效较好,毒性可以耐受,值得临床进一步研究。     

周剂量多西他赛联合顺铂、5-FU治疗晚期食管癌的临床观察

目的：观察周剂量多西他赛联合顺铂、5-FU治疗晚期食管癌的临床疗效及不良反应。方法：47例晚期食管癌患者,应用多西他赛30mg/m2静脉滴注第1、8、15天,顺铂20mg/m2静脉滴注第1-5天,5-FU500mg/m2静脉滴注第1-5天,每28天重复。治疗2个周期评价疗效,每周期评价毒性。结果：47例患者均可评价疗效。获CR 3例,PR 21例,总有效率（CR＋PR）为51.06%。所有患者中位疾病进展时间为149天,中位生存时间274天。主要不良反应为骨髓抑制,出现Ⅲ/Ⅳ度中性粒细胞减少13例（27.7%）,Ⅲ度血小板减少3例（6.4%）,Ⅲ度贫血5例（10.6%）,无治疗相关性死亡。结论：周剂量多西他赛联合顺铂、5-FU治疗晚期食管癌疗效较好,毒性可以耐受,值得临床进一步研究。     

三维适形放疗联合周剂量多西他赛治疗局部晚期非小细胞肺癌疗效观察

目的观察三维适形放疗(3DCRT)联合周剂量多西他赛化疗治疗局部晚期非小细胞肺癌(NSCLC)的近期疗效及耐受性。方法36例局部晚期NSCLC患者,实施3DCRT,照射剂量60Gy~72Gy。同步行多西他赛化疗,方案为每周1次多西他赛25mg/m2。36例患者共完成210个周期的化疗。结果36例患者全部完成治疗计划,CR为11.1%(4/36),PR为63.9%(23/36),有效率为75.0%(27/36),NC和PD分别为11.1%(4/36)和13.9%(5/36)。放射性肺炎和放射性食管炎发生率均为22.2%(8/36),白细胞下降发生率为63.9%(23/36)。结论三维适形放疗联合周剂量多西他赛同步治疗局部晚期非小细胞肺癌近期疗效较好,能明显提高患者的生活质量,不良反应能为大多数患者耐受。     

Phase II trial of weekly irinotecan plus cisplatin in advanced esophageal cancer.

PURPOSE: To evaluate the response, toxicity, survival, and quality of life in patients with unresectable or metastatic esophageal cancer treated with weekly irinotecan and cisplatin. PATIENTS AND METHODS: Thirty-five patients with metastatic or unresectable esophageal adenocarcinoma (23 patients) or squamous cell carcinoma (12 patients) were treated. No prior chemotherapy was allowed. The majority of patients had metastatic and bidimensionally measurable disease (34 patients each [97%]). Patients were treated with cisplatin 30 mg/m(2) and irinotecan 65 mg/m(2), repeated weekly for 4 weeks, followed by a 2-week rest period. Treatment was recycled every 6 weeks. Degree of dysphagia relief was monitored, and quality of life was measured prospectively using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 and Functional Assessment of Cancer Therapy-General instruments. RESULTS: Thirty-five patients were assessable for response and toxicity. Major objective responses were observed in 20 patients (57%; 95% confidence interval, 41% to 73%), including two complete responses (6%). Similar response rates were observed for adenocarcinoma (12 of 23 patients; 52%) and squamous carcinoma (eight of 12 patients; 66%). The median duration of response was 4.2 months (range, 1 to 8.8+ months). Median actuarial survival was 14.6 months (range, 1 to 15.2+ months). In 20 patients with dysphagia assessable at baseline, 18 (90%) noted either improvement or resolution of dysphagia on chemotherapy. Global quality of life improved in responding patients, primarily because of improvements in pain, emotional state, and relationships with family and friends. Toxicity was relatively mild and included only three patients (9%) with grade 4 neutropenia and four (11%) with grade 3 diarrhea. There were no treatment-related deaths. CONCLUSION: The combination of weekly cisplatin plus irinotecan had significant activity in metastatic esophageal carcinoma and resulted in significant relief of dysphagia. The regimen was well tolerated, with acceptable myelosuppression and rare treatment-related diarrhea. Further evaluation of the combination of weekly irinotecan and cisplatin, including the addition of other agents to this regimen, is indicated.     

Phase I trial of strictly time-scheduled gemcitabine and cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer

PURPOSE: Maximal therapeutic gain in xenograft sarcoma and toxicity for jejunal mucosa is time dependent for concurrent gemcitabine and radiotherapy (RT). We used a time-dependent schedule to determine the maximal-tolerated dose and dose-limiting toxicities (DLTs; Grade 4 hematologic or Grade 3 other toxicity). METHODS AND MATERIALS: Patients with pancreatic cancer (n = 33), periampullary carcinoma (n = 1), or bile duct cancer (n = 2) were treated with 3-day conformal RT with 50.4 Gy (tumor, lymphatics) plus a 5.4-Gy boost. Concurrent cisplatin (20 mg/m(2)/d on Days 1-5 and 29-33) and gemcitabine (initially 600 mg/m(2), weekly on Fridays 68 h before RT) were administered. Because of DLT, the doses were reduced to 500 mg/m(2) weekly and then 500, 400, or 300 mg/m(2) on Days 2, 5, 26, 33. RESULTS: DLT occurred at all dose levels of gemcitabine >300 mg/m(2). Fourteen patients were treated at the recommended Phase II dose of gemcitabine (300 mg/m(2)) without DLT. The response to chemoradiation allowed 10 of 30 initially unresectable patients with primary pancreatic carcinoma to undergo radical surgery, including a complete response in 2 cases. CONCLUSIONS: At the recommended Phase II dose, chemoradiation with gemcitabine and cisplatin can be administered safely in pancreatic carcinoma. However, at higher dose levels, toxicity is severe and frequent. Patients with a chance for conversion to resection could benefit from this schedule.