A Phase II Study of Sequential Neoadjuvant Gemcitabine and Paclitaxel, Radiation Therapy With Cisplatin and 5-Fluorouracil and Surgery in Locally Advanced Esophageal Carcinoma
Andrew M. LowyIrfan FirdausDebasish RoychowdhuryKevin P. RedmondJohn A. HowingtonJonathan SussmanMalek M. SafaSyed A. AhmadMichael F. ReedPatricia RoseLaura E. JamesAbdul Rahman Jazieh
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Abstract:
To evaluate the feasibility and efficacy of sequential neoadjuvant chemotherapy, chemoradiation, and surgery in patients with locally advanced esophageal cancer.There were 29 patients who received paclitaxel 150 mg/m2 and gemcitabine 3000 mg/m2 2 weeks apart. Two weeks later, patients received cisplatin 75 mg/m2 and 5-fluorouracil (5-FU) 1000 mg/m2/d continuous infusion for 4 days with concurrent radiotherapy in 15 fractions to a total dose of 4000 cGy. After 6 weeks, cisplatin and 5-FU were repeated at the above doses. After 4 to 6 weeks, patients were restaged and underwent surgical resection.All 29 patients completed the prescribed gemcitabine, paclitaxel, and radiation therapy. Febrile neutropenia occurred in 1 patient and 4 patients received growth factor support. After neoadjuvant treatment, 1 patient refused surgery, 23 underwent R0 resection (82%), while 5 developed progressive disease. Four patients developed anastomotic leaks (17%). Four patients had complete pathologic responses (14%) and 4 (14%) had only residual microscopic disease. Nine patients remain alive at a median follow-up of 48 months. Three-year survival for the entire cohort was 36%.This regimen was associated with a high rate of compliance and induction therapy had an acceptable toxicity profile. The R0 resection rate and 3-year survival data are similar to recently reported studies. While active, gemcitabine and paclitaxel induction therapy was associated with an increased rate of postoperative complications, but no increase in survival. Patterns of failure continue to demonstrate the need for regimens incorporating greater emphasis on systemic therapy for locally advanced esophageal cancer.Keywords:
Regimen
Neoadjuvant Therapy
Chemoradiotherapy
Chemoradiotherapy is a very important factor and one of the 2 pillars of esophageal cancer treatment. Although esophagectomy is the standard treatment for clinical stage Ⅰ(T1N0M0)esophageal cancer, chemoradiotherapy is reported to be effective. Currently, a phaseⅢ clinical trial is underway to compare patients who undergo esophagectomy and those who receive radical chemoradiotherapy. Esophagectomy after neoadjuvant chemotherapy is the standard treatment for clinical stageⅡ/Ⅲ(except for T4) esophageal cancer, whereas chemoradiotherapy is regarded as the standard treatment for patients who wish to preserve their esophagus, those who refuse surgery, and those with inoperable disease. Chemoradiotherapy, rather than surgical treatment, is usually selected for clinical stageⅣ (T4/M1LYM) esophageal cancer. While curability increases with chemoradiotherapy, late adverse events such as cardiopulmonary toxicity and safety problems with salvage treatment of cases with residual tumor or recurrent cancer have been observed. New irradiation techniques using radiation technology are being developed, such as intensity-modulated radiation therapy (IMRT). These innovations are expected to improve treatment results by avoiding irradiation of at-risk organs, without reducing the target radiation volume. New treatments, including salvage protocols, introduction of new radiotherapy equipment such as IMRT, and new drugs, are being developed, and further advances are anticipated.
Chemoradiotherapy
Esophagectomy
Radical surgery
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Chemoradiotherapy
Neoadjuvant Therapy
Complete response
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Chemoradiotherapy
Continuous Infusion
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Neoadjuvant Therapy
Esophagectomy
Complete response
Chemoradiotherapy
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The prognosis of patients with locally advanced esophageal cancer treated by surgery alone is poor. The neoadjuvant chemoradiotherapy is considered to improve the long-term survival of patients with locally advanced esophageal cancer. The combination of neoadjuvant chemoradiotherapy and surgery has been recommended to be the standard treatment for the locally advanced esophageal cancer in China even in Europe and America countries. However, available evidence suggests that only those who had histopathologic response seemed to benefit the most from neoadjuvant chemotherapy while non-responders even had rather worse outcome compared to patients with surgery alone. Therefore, predictive markers of response to neoadjuvant chemoradiotherapy in locally advanced esophageal cancer are highly significant and needed. These markers would allow a tailored treatment to guide non-responders to alternative preoperative therapies and ultimately avoid ineffective, costly and seriously cytotoxic treatments. Results of most studies on biomarkers for predicting response to neoadjuvant chemoradiotherapy in esophageal cancer are promising. The potential utilization of biomarkers in clinical practice is urgently expected and needed, which plays an important role in guiding and improving the individualization of multimodality therapy in locally advanced esophageal cancer.
Chemoradiotherapy
Neoadjuvant Therapy
Esophagectomy
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Gemcitabine and 5-fluorouracil are the only two compounds with reproducible activity against advanced pancreatic cancer (APC). We have evaluated a novel combination of gemcitabine and 5-fluorouracil on the clinical benefit response (CBR) end point. Eleven consecutive patients with symptomatic APC were entered in a two-stage phase II trial. Gemcitabine was administered by intravenous (i.v.) bolus injection at the dose of 1000 mg m–2 on days 1, 8, 15 and 5-fluorouracil 500 mg m–2 was given by continuous i.v. infusion on days 1–5. Treatment was repeated every 28 days. A CBR was achieved in 7/11 patients. The mean time to loss of CBR was 26.5 weeks (range 14–18, median 22). Toxicity was mild and no APC patient experienced WHO grade 3 toxicity. The gemcitabine/5-fluorouracil combination is well tolerated and produces a symptomatic relief in the majority of APC patients. © 2000 Cancer Research Campaign
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Pancreatic Disease
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瞄准：为了为作为放射利用低剂量 gemcitabine 的局部地先进的胰腺的癌症评估 chemoradiotherapy，抗体每周管理了两次。方法：我们执行了利用在 40 mg/m2 的剂量每周管理两次的 gemcitabine 的 chemoradiotherapy 的回顾的分析。在那以后，维护在 1000 mg/m2 的剂量，有 gemcitabine 的全身的化疗每周被管理因为有 1-wk 的 3 wk 休息直到疾病前进或不能接受的毒性发展了。结果：有局部地先进的 unresectable 的十八个病人胰腺的癌症被注册。三个那些病人不能继续治疗；一个病人在放射治疗期间有间质性肺炎，二个另外的病人在治疗的一个早阶段期间显示出肝转移或腹转移。中部的幸存是 15.0 瞬间，全面 1 年的幸存率是 60% ，当中部的没有前进的幸存是 8.0 瞬间时。显示出肿瘤开发的减小的亚群，超过 50% 为更好的预后显示出一个趋势；然而，包括年龄，性和表演地位的另外的参数没与幸存相关。死于肝转移和腹转移的组的中部的幸存分别地是 13.0 瞬间和 27.7 瞬间。结论：有管理的低剂量的 gemcitabine 的 Chemoradiotherapy 能每周两次对有局部地先进的胰腺的癌症的病人有效；然而，病人发展中肝转移有更坏的预后。另一 chemoradiotherapy 策略可能被需要因为那些病人例如开始管理一个或化疗的二个周期，没有远转移为盒子由 chemoradiotherapy 列在后面。
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We report a case of advanced esophageal cancer, which was treated by chemoradiotherapy combined with surgical treatment. Moreover, 14 advanced esophageal cancer patients treated by chemoradiotherapy are discussed. The chemoradiotherapy showed beneficial control of the tumor; however, it sometimes leads to esophageal stenosis and ulcer. We conclude that additional salvage surgery is needed for such complications.
Chemoradiotherapy
Salvage Surgery
Salvage therapy
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Esophageal cancer is one of the most common gastrointestinal cancers, and chemoradiotherapy is an important part of the multidisciplinary treatment for this disease. In recent years, 18Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) is widely used in esophageal cancer for delineation of gross tumor volume, local boost irradiation in the late stage of radiotherapy, and assessment of the pathologic remission rate after neoadjuvant chemoradiotherapy, response to definitive chemoradiotherapy, and prognosis. In this article, we review the application of FDG PET-CT in the chemoradiotherapy for esophageal cancer.
Key words:
Tomography, positron, emission; Fluorine-deoxyglucose; Esophageal neoplasms/chemoradiotherapy
Chemoradiotherapy
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