每周低剂量长春瑞滨、顺铂同步后程适形放射治疗局部晚期非小细胞肺癌的Ⅱ期临床研究

目的：探讨每周低剂量长春瑞滨（NVB）、顺铂（PDD）同步后程适形放射治疗局部晚期非小细胞肺癌（NSCLC）的可行性及观察其近期疗效和毒副反应。方法：首程经病理确诊的21例局部晚期NSCLC（根据UICC1997分期标准ⅢA期8例，ⅢB期13例）患者，符合KPS≥70分，年龄≤70岁，近3月体重下降≤5％，器官功能正常。全部患者均行每周1次低剂量NP方案（NVB12．5mg／m^2，PDD20mg／m^2）化疗，共7～9次。每周化疗结束后立即行放疗，先期同步常规放疗38Gy／19F，继之适形放疗推量至60～64Gy／6～7周；锁骨上区照射者推量至60Gy。结果：21例全部完成治疗计划，可行疗效评估，肺原发灶完全缓解（CR）14、3％（3／21），部分缓解（PR）61、9％（13／21），无变化和进展（NC＋PD）22．8％（5／21），总有效率（CR＋PR）为76．2％（16／21）。1年和2年生存率分别为76．2％、40、8％。3～4级白细胞减少发生率为33．3％（7／21）；3级血小板减少发生率为4．8％（1／21）；3级放射性食管炎9．6％（2／21）；无3级及以上放射性肺炎的发生。加用糖皮质激素后症状及影像学表现均好转，无治疗相关性死亡。结论：同期化疗加适形放疗治疗局部晚期NSCLC能为绝大多数患者耐受，有较好的近期疗效，值得临床进一步研究。     

Induction chemotherapy with docetaxel/cisplatin/5-fluorouracil followed by randomization to two cisplatin-based concomitant chemoradiotherapy schedules in patients with locally advanced head and neck cancer (CONDOR study) (Dutch Head and Neck Society 08-01): A randomized phase II study

PurposeTo study the feasibility of induction chemotherapy added to concomitant cisplatin-based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer (LAHNC).Patients and methodsLAHNC patients were treated with 4 courses of docetaxel/cisplatin/5-fluorouracil (TPF) followed by randomization to either cisplatin 100 mg/m² with conventional radiotherapy (cis100 + RT) or cisplatin 40 mg/m² weekly with accelerated radiotherapy (cis40 + ART). Primary endpoint was feasibility, defined as receiving ≥90% of the scheduled total radiation dose. Based on power analysis 70 patients were needed.Results65 patients were enrolled. The data safety monitoring board advised to prematurely terminate the study, because only 22% and 41% (32% in total) of the patients treated with cis100 + RT (n = 27) and cis40 + ART (n = 29) could receive the planned dose cisplatin during CRT, respectively, even though the primary endpoint was reached. Most common grade 3–4 toxicity was febrile neutropenia (18%) during TPF and dehydration (26% vs 14%), dysphagia (26% vs 24%) and mucositis (22% vs 57%) during cis100 + RT and cis40 + ART, respectively. For the patients treated with cis100 + RT and cis40 + ART, two years progression free survival and overall survival were 70% and 78% versus 72% and 79%, respectively.ConclusionAfter TPF induction chemotherapy, cisplatin-containing CRT is not feasible in LAHNC patients, because the total planned cisplatin dose could only be administered in 32% of the patients due to toxicity. However, all but 2 patients received more than 90% of the planned radiotherapy.Clinical Trials Information: NCT00774319.     

A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas.

BACKGROUND AND PURPOSE: This phase II study evaluated the efficacy and toxicity of weekly cisplatin along with concomitant boost accelerated radiation regimen in patients with locally advanced unresectable head and neck carcinoma. MATERIAL AND METHODS: A total of 94 patients (median age, 58 years) with UICC stage III (n = 19) and IV (n = 75) cancer of the oropharynx, larynx, hypopharynx and oral cavity were included. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1-40 and 1.5 Gy boost on days 25-40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m(2) weekly, for the first 4 weeks. RESULTS: Most patients (95%) received both radiation and chemotherapy according to protocol. Toxicity was manageable with grade III mucositis and pharyngeal-oesophageal toxicity in 85 and 50% of patients, respectively. Haematological toxicity was mild. Four patients (4%) died due to complications. With a median follow of 41 months, median overall survival and time to progression were 27 and 25 months, respectively. The estimated overall survival at 4 years was 41%. CONCLUSIONS: Concomitant boost accelerated radiation plus concurrent weekly cisplatin is a feasible schedule in patients with locally advanced unresectable head and neck carcinoma, with acceptable toxicity and survival data.     

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

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

健择联合顺铂合并放疗治疗进展期食管癌的临床研究

对41例初治进展期食管癌患者采用健择联合顺铂合并放射治疗。38例患者可以评估疗效和毒性。健择1000mg/m2,静脉滴入,d1、d8;顺铂20mg/m2,静脉滴入,d1~d4;同时合并放射治疗,每次2Gy,每周5次,共5周,总剂量为50Gy;化疗周期每21或28d重复。结果5例患者完全缓解,17例患者部分缓解,总有效率为58%;27例患者吞咽困难缓解,缓解率为71%;中位生存期为11·3个月;1、2年生存率分别为63%和45%;最常见的3、4度毒性是血小板下降(29%)、贫血(21%)、白细胞下降(24%)和食道炎(21%);无治疗相关死亡和3、4度的神经毒性。初步研究结果提示,健择加顺铂合并放疗方案治疗进展期食管癌耐受性好,疗效显著,值得临床广泛推广应用。     

同期放化治疗局部晚期非小细胞肺癌的临床研究

目的：观察同期放、化疗加适形(3D-CRT)补量放疗治疗局部晚期非小细胞肺癌的近期疗效和毒副反应。方法：36例局部晚期非小细胞肺癌(Ⅲa或Ⅲb期)患进入同期放化疗加适形补量组，全部患均行TP方案(紫杉醇140～160mg／m^2 d1给予；顺铂60～80mg／m^2 d1或分2～3d给予；21d为1个周期)化疗加常规放射治疗结合3DCRT补量同步治疗。结果：36例全部完成治疗计划，肺原发灶完全缓解（CR)占19．4%，部分缓解(PR)占75．0％，无变化和进展(NC PD)占5．6％，总有效率(CR PR)为94．4％；1～2级急性骨髓抑制发生率为89％，3～4级为36％。1～2级放射性食管炎和放射性肺炎的发生率分别为44％和11％，无3～4级发生率。12、18月生存率分别为78．9％、63．2％，12、18月局部控制率为68．4%、47．4％。结论：同期放化疗加适形补量治疗局部晚期非小细胞肺癌能为绝大多数患耐受，有较好的近期疗效。     

Accelerated postoperative radiotherapy with weekly concomitant boost in patients with locally advanced head and neck cancer.

BACKGROUND AND PURPOSE: To assess the feasibility and efficacy of accelerated 66-Gy postoperative radiotherapy (PORT) using a single-fraction regimen from Mondays to Thursdays and a concomitant boost on Friday afternoon sessions in patients with locally advanced head and neck cancer (LAHNC). PATIENTS AND METHODS: Between December 1997 and June 2002, 89 consecutive patients with pT1-pT4 and/or pN0-pN3 LAHNC were included. PORT was indicated in patients with positive surgical margins, T4 tumors, or extracapsular nodal infiltration. RT consisted of 66 Gy (2 Gy/fr) in 5 weeks and 3 days. Median follow-up was 21 months (range 2-59). RESULTS: Acute morbidity was acceptable: grade 3 mucositis in 20 (22%) patients, grade 3 dysphagia in 22 (25%) patients, and grade 3 skin erythema in 18 (20%) patients. Median weight loss was 2 kg (range 0-14.5). No grade 4 toxicity was observed. Late effects included grade 3 xerostomia in 6 (7%) patients, and grade 3 edema in 2 (2%) patients. Median time to locoregional relapse was 10 months (range 2-21). Two-year overall, cause-specific, and disease-free survival rates were 70% (95% confidence interval (CI) 59-81), 75% (95% CI 64-86), and 63% (95% CI 52-74), respectively. The 2-year actuarial locoregional control rate was 80% (95% CI 70-90). Distant metastasis probability at 4 years was 38% (95% CI 20-56). Multivariate analysis revealed that pT-classification (pT1-2 vs. pT3-4) and extranodal extension (0, 1 vs. 2 or more) were the two factors independently influencing the outcome. CONCLUSIONS: We conclude that reducing the overall treatment time using an accelerated PORT schedule including a once-weekly concomitant boost (six fractions per week) is easily feasible with excellent local control. Acute and late RT-related morbidity is acceptable. Given the disease progression pattern (distant metastases), adjuvant chemotherapy should be considered.     

Competing causes of death in patients with locoregionally advanced head and neck cancer treated with concomitant boost radiation plus concurrent weekly cisplatin

Background

This study analyzes the morbidity and the contribution of different causes of death to the outcome of patients with locally advanced head and- neck cancer after weekly cisplatin plus concomitant boost accelerated radiation treated in our center.

Materials and methods

Ninety-four patients with locally advanced head and neck carcinoma were included in this phase II trial consisting of concomitant boost radiation plus concurrent weekly cisplatin. The 43 patients treated in our centered with long-term follow-up were analyzed. Patients received radiotherapy with a concomitant boost scheme (1.8 Gy on days 1–40 and 1.5 Gy boost on days 25–40 with a total dose of 72 Gy) and concurrent cisplatin, 40 mg/m² weekly, for the first 4 weeks.

Results

Most patients (93 %) received both radiation and complete chemotherapy according to protocol. Severe late toxicity presented were subcutaneous (5 %), larynx (2 %) and esophagous (5 %). Grade I–II late toxicity included mainly xerostomy (30 %), skin (16 %) and mucosal (16 %) toxicity. With a median follow-up of 95 months (9–135), the median overall survival and progression-free survival were 26 and 19 months, respectively (95 % CI 1–52; and 95 % CI 0–45); 60 % of the patients died because of head and neck cancer and 12 % of a second neoplasm, while 27 % of non-cancer patients died.

Conclusions

Patients with locoregionally advanced head and neck cancer treated with concomitant boost accelerated radiation plus chemotherapy show significant risks of mortality from causes other than disease progression.     

Concomitant weekly cisplatin and altered fractionation radiotherapy in locally advanced head and neck cancer

BACKGROUND:

Both concomitant chemotherapy and altered fractionation radiotherapy (RT) have been shown to improve outcomes for patients with locoregionally advanced head and neck squamous cell carcinomas. However, both strategies also increase acute toxicity, and it is questionable whether the 2 can be safely combined. Traditional concomitant chemotherapy regimens include high‐dose cisplatin given at 100 mg/m² every 3 weeks. The authors' purpose was to report efficacy and toxicity after weekly cisplatin (30 mg/m²/wk) concurrent with altered fractionation RT.

METHODS:

One hundred twenty‐one patients with American Joint Committee on Cancer stages II (3%), III (13%), or IV (84%) squamous cell carcinomas of the oropharynx (70%), hypopharynx (20%), or larynx (10%) were treated between 2000 and 2006 at the University of Florida with hyperfractionated RT (55 patients) or concomitant boost RT (66 patients) and concomitant cisplatin (30 mg/m²/wk).

RESULTS:

Median follow‐up was 2.9 years; median follow‐up on survivors was 3.6 years. Seventy‐nine percent of patients completed ≥6 cycles of chemotherapy; 94% received ≥7200 centigrays. Seven (6%) patients changed from cisplatin to carboplatin because of bone marrow toxicity. Gastrostomy tube feeding was required in 54% of patients either before (16%) or during RT (38%). Two (1.6%) patients died from therapy‐related complications. The 5‐year outcomes were: local control, 83%; locoregional control, 79%; distant metastasis‐free survival, 88%; cause‐specific survival, 76%; and overall survival, 59%. Seven (6%) patients had severe late complications. Three (3%) patients required a permanent gastrostomy tube.

CONCLUSIONS:

Concomitant weekly cisplatin with altered fractionation RT is a safe and effective treatment regimen. Cancer 2010. © 2010 American Cancer Society.     

Extended-field radiotherapy and high-dose-rate brachytherapy in carcinoma of the uterine cervix: clinical experience with and without concomitant chemotherapy

BACKGROUND: It has long been recognized that many patients with locally advanced carcinoma of the cervix harbor occult paraaortic metastases. A randomized study demonstrated that elective paraaortic irradiation improved survival and reduced distant metastases. More recently, concomitant chemotherapy with pelvic irradiation has improved survival among patients with locally advanced carcinoma of the cervix. This has led to a reexamination of the role of extended-field irradiation. An important issue is the toxicity of concomitant chemotherapy and extended-field radiotherapy. The authors report a retrospective analysis of their experience with extended-field radiotherapy and high-dose-rate brachytherapy with or without concomitant chemotherapy. METHODS: The authors treated 54 women with biopsy-confirmed carcinoma of the cervix using extended-field radiotherapy and high-dose-rate brachytherapy with or without concomitant chemotherapy. The histology was squamous cell carcinoma in 49 patients (91%) and nonsquamous cell carcinoma in 5 patients (9%). The median size of the primary tumor was 7 cm (range, 3-10 cm). Each patient received 45 grays (Gy) of external beam radiotherapy to the pelvis and the paraaortic region, followed by a parametrial boost (9 Gy) in the patients with disease extension to the parametrium or the pelvic side wall(s). Each patient also underwent two applications of high-dose-rate brachytherapy, 1 week apart. The median dose delivered to Point A from each application was 9 Gy. Forty-four of the 54 patients (81%) received concomitant chemotherapy (cisplatin, 20 mg/m(2)/day for 5 days) during the first and the fourth weeks of external beam radiotherapy, and once after the second high-dose rate application. Chemotherapy was not assigned randomly. RESULTS: One of the 10 patients (10%) treated without chemotherapy experienced acute toxicity, whereas 41 of 44 patients (93%) who received chemotherapy suffered from acute toxicity, including hematologic toxicity, gastrointestinal toxicity, and deep venous thrombosis. During a median follow-up period of 28 months (range, 12-70 months), 6 of the 54 patients have died (11%). The actuarial rate of local control at 3 years is 100% among the patients treated without chemotherapy, compared with 85% among those receiving chemotherapy. No one failed in the paraaortic region. The actuarial rates of freedom from distant metastases are 90% and 95% among the patients treated without and with chemotherapy, respectively. The actuarial incidence of late toxicity is 10% among the patients treated without chemotherapy and 6% among those receiving chemotherapy. CONCLUSIONS: The regimen of extended-field radiotherapy with concomitant cisplatin and high-dose-rate brachytherapy produced substantial acute toxicity, but its long-term toxicity is low and the preliminary tumor control excellent, albeit with limited follow-up. Only prospective, randomized trials can evaluate whether these results are truly better than those of pelvic radiotherapy with concomitant chemotherapy, or those of other regimens of extended-field radiotherapy with concomitant chemotherapy. Cancer 2003;97:1781-8.     

Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer

Recent studies have suggested the superiority of concomitant over sequential administration of chemotherapy and radiotherapy. Docetaxel and cisplatin have demonstrated efficacy in advanced non-small-cell lung cancer (NSCLC). This study evaluated the safety, toxicity, and antitumour activity of docetaxel/cisplatin with concurrent thoracic radiotherapy for patients with locally advanced NSCLC. Patients with locally advanced NSCLC (stage IIIA or IIIB), good performance status, age or=3 toxicities of 71, 60, 24, and 19%, respectively. Toxicity was significant, but manageable according to the dose and schedule modifications. Dose intensities of docetaxel and cisplatin were 86 and 87%, respectively. Radiotherapy was completed without a delay in 67% of 42 patients. The overall response rate was 79% (95% confidence interval (CI), 66-91%). The median survival time was 23.4+ months with an overall survival rate of 76% at 1 year and 54% at 2 years. In conclusion, chemotherapy with cisplatin plus docetaxel given on days 1, 8, 29, and 36 and concurrent thoracic radiotherapy is efficacious and tolerated in patients with locally advanced NSCLC and should be evaluated in a phase III study.     

Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy.

PURPOSE: To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. PATIENTS AND METHODS: From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. RESULTS: There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. CONCLUSION: The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.     

Phase II study of chemoradiotherapy with S-1 and low-dose cisplatin for inoperable advanced gastric cancer

PURPOSE: The results of a pilot study using S-1/low-dose cisplatin/radiotherapy led us to hypothesize that the initial chemoradiotherapy regimen would induce a 70% efficacy rate with a 10% pathologic complete response rate. PATIENTS AND METHODS: Only patients with unresectable or incurable advanced gastric cancer were eligible. The patients received induction S-1 and cisplatin therapy with radiotherapy followed by chemotherapy alone. RESULTS: Of the 30 patients recruited and assessed, 29 were eligible for clinical evaluation of measurable lesions. The response rate was 65.5%, with 19 with a partial response, 8 with no change, and 2 with progressive disease of 29 patients. Of the 30 patients recruited, 10 (33.3%) underwent stomach resection and D2 LN dissections. The pathologic complete response rate was 13.3% (4 patients), and the R0 resection rate was 100% (10 patients). The survival analysis showed a median survival time of 25 months. Grade 3 toxicity occurred in 66.7% for leukocytopenia, 33.3% for thrombocytopenia, 23.3% for nausea and appetite loss, and 6.7% for anemia, diarrhea, and renal dysfunction. Although all the patients had been hospitalized with a poor performance status with a giant tumor, 97% (29 of 30) could be discharged after the first cycle, resulting in an improvement in quality of life. CONCLUSION: Chemoradiotherapy could be a powerful regimen for controlling tumor progression in advanced gastric cancer, improving patients' quality of life with tolerable toxicity. A complete histologic response rate of >10% would be expected, even for large tumors with metastatic lesions.     

Treatment of HIV-associated invasive anal cancer with combined chemoradiation

There is an increased frequency of invasive anal cancer in HIV-seropositive men. Early treatment strategies in this patient group employed reduced dosages of chemotherapy or radiotherapy alone to reduce toxicity. Since 1989 we have used combined modality treatment consisting of chemotherapy 5-fluorouracil (5-FU) and mitomycin C, and concomitant radical radiotherapy to the pelvis (38-51 Gy in 20-30 fractions), with most patients receiving a perineal boost (10-18 Gy). 12 homosexual HIV-positive men have been treated. The median CD4 count at diagnosis of anal cancer was 209 cells/microl (range: 29-380 cells/microl), 5 had prior AIDS defining diagnoses. No patients had metastatic disease. Complete remissions were obtained in 9/11 evaluable patients and in 1 further patient following surgery. 2 patients relapsed both within 6 months of diagnosis. At a median follow-up of 4.8 years (range: 0.4-10 years), 4 patients have died (2 from anal cancer, 1 from treatment-related consequences and 1 from opportunistic infection in remission). Actuarial 2-year survival is 60% (95% confidence interval (CI): 29-91%). Grade 3 haematological toxicity was recorded in 3 patients, grade 4 and 5 gastrointestinal toxicity in 1 patient each and grade 3 skin toxicity in 1 patient. Radical chemoradiation may be given safely at conventional doses in HIV-positive patients, with a high complete response rate.     

长春瑞滨和顺铂联合同步放疗治疗局部晚期非小细胞肺癌临床研究

目的观察和评价长春瑞滨和顺铂联合同步放疗治疗局部晚期非小细胞肺癌的疗效和不良反应.方法 50例局部晚期非小细胞肺癌患者随机分为同步治疗组和序贯治疗组.同步治疗组累及野常规分割放射治疗:DT 60～64 Gy/30～32次/42～45 d.同步化疗:长春瑞滨25 mg/m2,d1,8,22,29;顺铂25 mg/m2,d1,2,8,9,22,23,29,30.同步放化疗后继续接受辅助化疗.序贯治疗组单纯累及野放疗同前,辅助化疗同前.结果同步治疗组和序贯治疗组的有效率分别为76.0%和36.0%;1,3年总生存率分别为64.0%、36.0%和37.5%、11.1%;1,3年无进展生存率分别为40.0%、16.0%和18.8%、0,差异均有显著性.结论长春瑞滨和顺铂联合同步常规分割放射治疗是局部晚期非小细胞肺癌较为理想的治疗模式.     

Phase 2 trial of preoperative irinotecan plus cisplatin and conformal radiotherapy,followed by surgery for esophageal cancer

BACKGROUND:

Esophagectomy for locally advanced esophageal cancer (LAEC) is associated with limited survival. Trimodality therapy yields a small survival advantage, with cisplatin and 5‐fluorouracil regimens most frequently studied. Newer regimens may impact these poor outcomes. This phase 2 trial assessed the feasibility and efficacy of induction chemoradiotherapy with cisplatin and irinotecan followed by esophagectomy.

METHODS:

Patients with LAEC of the thoracic esophagus or gastroesophageal junction underwent chemotherapy with preoperative irinotecan (65 mg/m²) plus cisplatin (30 mg/m²) on Weeks 1, 2, 4, 5, 7, and 8 with concurrent conformal radiotherapy (40 grays [Gy]/20 fractions during Weeks 4‐7) and external beam boost (10 Gy/5 fractions at Week 8). Esophagectomy was performed between Weeks 12 and 16. Pathologic response was the primary endpoint with follow‐up data on progression, survival, and toxicity as secondary endpoints.

RESULTS:

Fifty‐two patients were enrolled from November 2002 to October 2005. Nineteen patients had American Joint Committee on Cancer stage II, 22 had stage III, and 11 had stage IVA disease. Grade 3 to 4 toxicity (graded according to the National Cancer Institute Common Toxicity Criteria 2.0) during induction included neutropenia (36%), febrile neutropenia (8%), diarrhea (10%), and esophagitis (4%). Three patients withdrew from treatment due to toxicity. There was 1 treatment‐related death. Clinical responses included complete response in 2%, partial response in 30%, stable disease in 62%, and progressive disease in 6% of patients. Dysphagia improved/resolved in 72% of patients during induction. Forty‐three patients underwent esophagectomy and 7 (16%) achieved pathologic complete responses. Median and 3‐year overall survival for patients receiving trimodality therapy was 36 months and 51%, respectively.

CONCLUSIONS:

In LAEC, concurrent irinotecan/cisplatin and radiotherapy followed by esophagectomy is reported to be associated with dysphagia improvement in 72% of patients, a significant but manageable toxicity profile, and encouraging survival compared with historic controls. Cancer 2010. © 2010 American Cancer Society.     

Concomitant chemotherapy and external radiotherapy plus brachytherapy for locally advanced esophageal cancer: results of a retrospective multicenter study

AIMS AND BACKGROUND: In October 1995, the Piedmont AIRO (Italian Society of Radiation Oncology) Group started a multi-institutional study of radiochemotherapy on locally advanced esophageal cancer, characterized by external radiotherapy followed by an intraluminal high dose-rate brachytherapy boost. Most patients were re-evaluated for surgery at the end of the program. The primary aim of the study was to assess efficacy of curative radiochemotherapy regarding overall survival and local control rates. The secondary aim was to evaluate the ability of radiochemotherapy to make resectable lesions previously considered inoperable. METHODS AND STUDY DESIGN: Between January 1996 and March 2000, 75 patients with locally advanced esophageal cancer were enrolled. All were treated with definitive radiotherapy; due to age or high expected toxicity, chemotherapy was employed only in 53 of them. Treatment schedule consisted of 60 Gy external radiotherapy (180 cGy/d, 5 days/week for 7 weeks) concomitant with two 5-day cycles of chemotherapy with cisplatin and fluorouracil (weeks 1 and 5). One or two sessions of 5-7 Gy intraluminal high dose-rate brachytherapy were carried out on patients whose restaging showed a major tumor response. Surgery was performed in 14 patients. RESULTS: At the end of radiotherapy, dysphagia disappeared in 46/75 cases (61%), and in 20/75 (27%) a significant symptom reduction was recorded. Complete objective response at restaging after radiotherapy was obtained in 33% of patients and a partial response in 53%. At the end of the multimodal treatment program, including esophagectomy, complete responses were 34 (45%); 4 of 14 (28.5%) cases proved to be disease free (pT0) at pathological examination. No G3-G4 toxicity was recorded. Two- and 5-year overall survival rates of all patients were, respectively, 38% and 28%; 2- and 5-year local control rates were, respectively, 35% and 33%. In a subgroup of 20 nonsurgical patients in complete response after radiochemotherapy, the overall survival rate at 3 and 5 years was 65% and the local control rate at 3 and 5 years was 75%. According to multivariate analysis, prognostic factors for survival were Karnofsky index and esophagectomy. CONCLUSIONS: For patients with locally advanced disease, radiochemotherapy showed improved clinical and pathologic tumor response and survival compared to surgery or radiotherapy alone. Intraluminal brachytherapy with a small fraction size allows an increased dose to the tumor without higher toxicity. Esophagectomy following radiochemotherapy could improve survival rates compared to definitive radiochemotherapy, but it is necessary to optimize selection criteria for surgery at the re-evaluation phase.     

局部晚期鼻咽癌同期放化疗的疗效分析

目的评估同期放化疗方案对局部晚期鼻咽癌患者的疗效、急性毒性反应、依从性和晚期损伤情况。方法74例Ⅲ、Ⅳ期中国人种局部晚期鼻咽癌患者,按照北美Intergroup0099方案接受了同期放疗加辅助化疗的治疗,其急性与晚期毒性反应采用美国放射治疗协作组织（RTOG）的标准进行评价。结果74例患者的5年生存率和无瘤生存率分别为71．3％和43．5％。无5级毒性反应发生,3,4级急性毒性反应主要为造血系统25例,占33．8％;咽部黏膜19例,占25．7％;放疗区皮肤损伤6例,占8．1％。完成放疗、同期放化疗和全部化疗者分别为100．0％、75．7％和47．3％;3—4级晚期并发症主要为唾液腺损伤（17例）、听力损伤（13例）、皮肤及皮下组织损伤（7例）,晚期损伤的5年累积发生率为44．3％。结论与常规放射治疗相比,同期放化疗方案有助于中国人种局部晚期鼻咽癌患者疗效的提高,其急性毒性反应有所增加,晚期损伤基本相同。     

Induction chemotherapy with paclitaxel and cisplatin and CT-based 3D radiotherapy in patients with advanced laryngeal and hypopharyngeal carcinomas--a possibility for organ preservation.

BACKGROUND: To evaluate the effect of paclitaxel/cisplatin induction chemotherapy (ICHT) and CT-based radiotherapy (RT) on larynx preservation, tumor control, and survival in patients with larynx/hypopharynx carcinoma eligible for total laryngectomy (TL) or TL plus partial pharyngectomy (TLPP). PATIENTS AND METHODS: Fifty patients eligible for TL or TLPP were enrolled onto a prospective study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22). In patients with complete or partial tumor response RT (69.9 Gy in 5.5 weeks at the gross tumor, 50.4 Gy in the lymphatic drainage; single dose: 1.8 Gy, concomitant boost: 1.5 Gy) was applied. Non-responders had TL/TLPP and RT with total doses adapted to the radicality of tumor resection (56-70 Gy). RESULTS: The response rate to ICHT was 88% (10% complete, 78% partial response). At a median follow-up period of 25 months the larynx preservation rate was 84%. The 2-year local-regional control rate was 91% and the 2-year overall survival rate was 72.3%. The 3-year estimate to survive with functional larynx is 60%. CONCLUSION: In a large portion of patients eligible for TL or TLPP the larynx was preserved by paclitaxel/cisplatin ICHT and 3D RT.     

Nedaplatin and 5-fluorouracil combined with radiotherapy for advanced esophageal cancer

We conducted a pilot study of nedaplatin + 5-fluorouracil (5-FU) combined with radiotherapy for 29 patients with primary advanced (stage IV) esophageal cancer. A complete remission (CR) was obtained in 4 (14%) and a partial response in 13 patients (response rate: 59%). The median survival time and one-year survival rate were 238 days and 34.5%, respectively. Of the 29 patients, 24 (83%) completed the treatment schedule and toxicity of stomatitis and the like was infrequent. In conclusion, these results suggest that the efficacy of nedaplatin + 5-FU combined with radiotherapy might not differ from that of cisplatin + 5-FU combined with radiotherapy. Clearly, the usefulness of this combined therapy needs to be assessed in multicenter phase III trials.