Neoadjuvant therapy with weekly docetaxel and cisplatin, 5-fluorouracil continuous infusion, and concurrent radiotherapy in patients with locally advanced esophageal cancer produced a high percentage of long-lasting pathological complete response

Cancer ◽  
2012 ◽  
Vol 119 (5) ◽  
pp. 939-945 ◽  
Author(s):  
Felice Pasini ◽  
Giovanni de Manzoni ◽  
Andrea Zanoni ◽  
Antonio Grandinetti ◽  
Carlo Capirci ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Continuous Infusion ◽  
Neoadjuvant Therapy ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Esophageal Cancer ◽  
Weekly Docetaxel ◽  
Concurrent Radiotherapy ◽  
Locally Advanced Esophageal Cancer

Phase II cisplatin, irinotecan, cetuximab and concurrent radiation therapy followed by surgery for locally advanced esophageal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4064-4064 ◽  
Author(s):  
P. C. Enzinger ◽  
T. Yock ◽  
W. Suh ◽  
P. Fidias ◽  
H. Mamon ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Radiation Therapy ◽  
Phase Ii ◽  
Locally Advanced ◽  
Complete Response ◽  
Tumor Location ◽  
Advanced Esophageal Cancer ◽  
Early Results ◽  
Ecog Ps ◽  
Locally Advanced Esophageal Cancer

4064 Background: Weekly irinotecan, cisplatin, and concurrent radiation therapy is a well-tolerated, active regimen in locally advanced esophageal cancer. (Ilson. JCO 2003) Cetuximab, an EGFR inhibitor, is a potent radiation sensitizer in head and neck cancer. (Bonner. Proc ASCO 2004) Methods: In this phase II trial, patients (pts) with T2–4N0–1M0–1A esophageal adenocarcinoma (A) or squamous cell carcinoma (S) receive 5040 cGy/28 fractions of radiation therapy (RT) and concurrent weekly cisplatin 30mg/m2 plus irinotecan 65 mg/m2 on weeks 1, 2, 4, and 5, followed by surgery 4–8 weeks after completion of RT. Additionally, pts receive weekly infusions of cetuximab 250 mg during RT, up to one week before surgery, and for 6 months following surgery. Results: Seventeen pts have been entered: male: female = 14:3, median age 54, ECOG PS 0:1 = 6:11, A:S = 17:0, stage IIA:IIB:III:IVA = 6:1:8:2, tumor location-esophagus-mid:lower:gastroesophageal junction = 1:4:12, >10% weight loss-yes:no = 8:9. Of 17 pts entered, 15 pts have proceeded to surgery, 1 pt died from Aspergillus infection resulting in respiratory failure and sepsis, and 1 pt is pending surgery. Of the 15 pts who underwent surgery, 2 (13%) had a complete pathologic response; pathologic stage for other pts: 0 = 1, I = 3, IIA = 3, IIB = 1, III = 4, IV = 1. Grade III/IV toxicity (17 pts) was: diarrhea 9 pts, neutropenia 9 pts, febrile neutropenia 5 pts, anorexia 5 pts, vomiting 4 pts, fatigue 3 pts, mucositis 1 pt. Chemotherapy dose attenuation was required for diarrhea in 5 pts, for neutropenia in 4 pts, and for folliculitis in 1 pt. One patient was removed from study during week 6 for prolonged diarrhea/ dehydration. Due to the 2-step design of the trial, accrual is on hold pending a 3rd required pathologic CR in the first 17 patients. Conclusions: Compared to other trials of irinotecan, cisplatin, radiation therapy, and surgery in similar groups of esophageal cancer patients, early results for this combination with cetuximab suggest a lower complete response rate and higher overall toxicity. Additional data will be available at ASCO. Supported by Bristol-Myers Squibb. No significant financial relationships to disclose.

Survivin expression in esophageal cancer: Association with histomorphological response to neoadjuvant therapy and prognosis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4536-4536 ◽  
Author(s):  
D. Vallboehmer ◽  
E. Kuhn ◽  
J. Brabender ◽  
R. Metzger ◽  
U. Warnecke-Eberz ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Protein Expression ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Survivin Expression ◽  
Neoadjuvant Radiochemotherapy ◽  
Advanced Esophageal Cancer ◽  
Survivin Protein ◽  
Histopathologic Response ◽  
Locally Advanced Esophageal Cancer

4536 Background: The poor prognosis associated with locally advanced esophageal cancer prompted an evaluation of combined modality treatments including neoadjuvant radiochemotherapy in combination with surgery. However, it has been well established that only patients with a complete pathological response to neoadjuvant therapy will have a significant survival benefit. Therefore, predictive markers to allow a tailored radiochemotherapy are needed. The aim of this study was to examine the association of the protein expression of survivin, an inhibitor of apoptosis, with histopathologic response to neoadjuvant radiochemotherapy and prognosis of patients with locally-advanced esophageal cancer. Methods: 59 patients with esophageal cancer (cT2–4, Nx, M0) received neoadjuvant radiochemotherapy (cisplatin, 5-FU, 36 Gy) followed by esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10 % and as minor response when resected specimens contained more than 10 % of residual vital tumor cells. Pre- and post-therapeutic intratumoral protein expression of survivin was determined and correlated with clinicopathologic parameters. Results: The pre-therapeutic intratumoral survivin protein expression was not associated with any clinicopathologic factor, including histopathologic response and prognosis. Survivin protein expression was significantly reduced during neoadjuvant therapy, showing lower levels in post-therapeutic tumor samples (p<0.01). Higher postoperative survivin levels were significantly associated with a higher ypT-stage (p<0.009), a poorer histopathologic response (p<0.01) and a shorter overall survival (p<0.028). Conclusions: The intratumoral protein expression of survivin was significantly down-regulated during neoadjuvant therapy, whereas a higher survivin level after pre-operative therapy was significantly associated with a worse histopathologic response and prognosis. Therapeutic strategies which are able to reduce survivin expression or to block survivin mediated pathways might increase the histopathologic response rate and prognosis in the multimodal therapy of patients with locally-advanced esophageal cancer. No significant financial relationships to disclose.

Outcomes of recurrence after complete response to definitive chemoradiotherapy for stage II/III (non–T4) esophageal squamous cell carcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 179-179
Author(s):  
Hiroki Kuwabara ◽  
Ken Kato ◽  
Yusuke Sasaki ◽  
Naoki Takahashi ◽  
Hirokazu Shoji ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Survival Time ◽  
Cox Regression ◽  
Performance Status ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Esophageal Cancer ◽  
Locoregional Failure ◽  
Distant Failure ◽  
Locally Advanced Esophageal Cancer

179 Background: Recurrence after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer is associated with poor outcome. We examined patterns of recurrence and clinical outcomes in patients with recurrence after complete response (CR) to dCRT. Methods: We retrospectively investigated 238 patients who had achieved initial CR after dCRT for locally advanced esophageal cancer between January 2000 and December 2010. From among these patients we selected 95 who had developed disease recurrence after CR. Overall survival was defined as survival time from recurrence to death and was calculated by using the Kaplan-Meier method. Univariate and multivariate analyses were performed with the Cox regression model to determine prognostic factors for survival. Results: The characteristics of the 95 patients were as follows: male: female = 84:11; median age = 64 years (range 46 to 80); clinical stage at diagnosis (UICC 6th edition) IIA/IIB/III = 20/31/44; and performance status at recurrence (0/1) = (51/44). Primary CRT consisted of 5-FU+cisplatin (n = 87), 5-FU+nedaplatin (n = 3), S-1+cisplatin (n = 3), 5-FU+cisplatin+ nimotuzumab (n = 1), or docetaxel (n = 1). The pattern of recurrence was locoregional failure (n = 53) or any distant failure (n = 42). Median time from the start of dCRT to recurrence was 13.0 months, and median survival time from recurrence to death was 19.6 months. Median survival time according to the pattern of failure was 34.7 months (locoregional failure) or 17.0 months (any distant failure). Application of the Cox regression model, including the additional prognostic variables of age, ECOG performance status, number of organs in which metastases were present, and LDH, revealed that any distant failure (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.2 to 4.1; P = 0.01) and recurrence before 13.0 months (HR 2.1; 95% CI 1.2 to 3.6; P = 0.01) were predictors of poor overall survival. Conclusions: Early recurrence and any distant failure were associated with poor prognosis after CR to dCRT for locally advanced esophageal cancer.

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