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: a phase 2 study.

BACKGROUND: This phase 2 study was aimed at defining the pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, continuous infusion (c.i.) of 5-fluorouracil (5-FU) and concomitant radiotherapy (RT) in untreated stage II-III adenocarcinoma and squamous cell carcinoma of mid-distal thoracic esophagus. METHODS: The schedule consisted of a first phase of chemotherapy alone and of a second phase of concurrent chemoradiation. Doses were as follows: docetaxel 35 mg/m(2) and cisplatin 25 mg/m(2) on days 1, 8, 15, 29, 36, 43, 50, and 57 plus 5-FU c.i. (180 mg/m(2) on days 1-21 and 150 mg/m(2) on days 29-63); RT (50 Gy) started at day 29. Surgery was planned 6 to 8 weeks after the completion of chemoradiation. RESULTS: A total of 74 patients were enrolled; pathological complete remission (pCR) was found in 47% (35 of 74) and near pCR (microfoci of tumor cells on the primary tumor without lymph nodal metastases) (pnCR) in 15% of the patients (11 of 74). Grade 3-4 neutropenia, nonhematological toxicity, and toxic deaths occurred in 13.5%, 32.4%, and 4% of the patients, respectively. Median follow-up was 55 months (range, 3-108 months). Median survival of all 74 patients was 55 months, whereas it was not reached in the pCR subset. The 3- and 5-year survival rates were, respectively, 83% and 77% for pCR, 73% and 44% for pnCR, and 21% and 14% for Residual Tumor subsets (P < .001). CONCLUSIONS: This study shows that 1) this intensive weekly schedule produced a high pathological response rate, 2) responders had high and long-term durable survival rates.

Chemoradiotherapy followed by surgery for squamous cell carcinoma of the thoracic esophagus with clinical evidence of adjacent organ invasion.

BACKGROUND: The role of surgery for esophageal squamous cell carcinoma (SCC) with clinical evidence of adjacent organ invasion (cT4) is a debated issue. This study was aimed at analyzing our experience with chemoradiotherapy (CRT) followed by surgery as treatment for non-metastatic cT4 SCC of the thoracic esophagus. METHODS: The results of 51 patients consecutively treated at the First Department of General Surgery, University of Verona, from January 1987 to December 2004 were analyzed. RESULTS: The most frequently clinically involved structures were the trachea (43.1%), the main left bronchus (17.6%), and the thoracic aorta (15.7%). CRT was completed in all but one of the patients (98.0%) without toxicity-related deaths. After completion of induction treatment 49 patients underwent surgery (96.1%), and resection was possible in 40 patients (78.4%) but R0 surgery was rarely obtained (39.2%). Pathologic downstaging was achieved in 18 cases (35.3%) while a major response (responders) was observed in 10 patients (19.6%) and a complete response (pT0N0) in 7 (13.7%). The overall median survival time was 11.1 months with a 3-year survival rate of 8.8%. A significantly better survival (P < 0.001) was observed after a R0 resection (median: 22.3 months; 3-year survival: 25.4%; P < 0.001) and for responders (median: 33.1 months; 3-year survival: 25.7%; P = 0.019). CONCLUSIONS: Aggressive multi-modal therapy with CRT followed by surgery in cT4 SCC of the thoracic esophagus is feasible. Surgery should be limited to patients with significant response to induction treatment and a high probability of R0 resection.

Induction chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus: impact of increased dosage on long-term results.

BACKGROUND: This study analyzed the impact on long-term results of an increase in the dosage of an induction chemoradiotherapy protocol for squamous cell carcinoma (SCC) of the thoracic esophagus. METHODS: Two groups were considered among 177 patients who underwent preoperative chemoradiotherapy for SCC of the thoracic esophagus. Group A includes 111 patients (from 1987 to 1995) who were submitted to cisplatin and 5-fluorouracil (two cycles) and radiotherapy (3,000 cGy). Group B includes 66 patients (from 1995 to 2002) in which the doses were raised both in terms of chemotherapy (three cycles) and radiotherapy (5,000 cGy). RESULTS: The induction treatment was completed in most of the patients (92.1%) with an acceptable treatment-related mortality (2.6%). Surgery was accomplished in 148 patients; 78.4% and 92.4% in groups A and B, respectively (p = 0.015). The postoperative in-hospital mortality was 8.8%. Tumor resection was possible in 91.8% with a better R0-resection rate for group B (83.9%; p = 0.004). Responders represented 34.9% of the patients with 20.1% of "complete" responses (29.5% in group B; p = 0.018). The overall 5-year survival rate was improved in group B (30.2%; p = 0.017), and when survival analysis was restricted to responders (70.1%; p = 0.027). CONCLUSIONS: No differences in feasibility and complication rate were observed during the two study periods. A higher rate of R0-resections was achieved in group B. The increased dosage led to an increased rate of complete responses and to an improved overall 5-year survival.

[Preliminary results of neoadjuvant treatment of adenocarcinoma of the gastro-esophageal junction]. / Risultati preliminari del trattamento neoadiuvante dell'adenocarcinoma del giunto esofago-gastrico.

The prognosis of adenocarcinoma of the gastro-oesophageal junction is poor and only surgery yields long-term survival in no more than 30% of patients. We tested a new neoadjuvant chemo-radiotherapy regimen based on the administration of weekly docetaxel and cisplatin and continuous infusion of 5-FU with concurrent radiotherapy in order to evaluate its feasibility and efficacy. Thirty-three patients enrolled in a dose-finding study and observed at the 1st Division of General Surgery of the University of Verona between January 2000 and October 2003 underwent neoadjuvant chemo-radiotherapy for gastro-oesophageal junction adenocarcinoma (Siewert type I and II). The induction treatment was completed in 97.0% of cases with no treatment-related mortality. After completion of chemo-radiation 30 patients underwent surgery (90.9%) while three patients did not (progression in 2 cases and chemotherapy toxicity in one). Two operated patients did not undergo resection because of liver metastasis at laparotomy (respectability: 84.8%) and 3 more cases had incomplete tumour resection (R0-resectability: 75.8%). No postoperative in-hospital mortality was observed. A complete response (pT0N0) was achieved in 7 cases (23.3%) while minimal residual disease without evidence of lymph node involvement was found in a further 5 cases (16.7%). Worthy of note is the high rate of positive histopathological responses in the later period (6 out of 8) with 4 cases presenting complete responses. This protocol regimen proved to be feasible and well tolerated. Surgery-related deaths and morbidity were not increased. A high rate of positive pathological responses was obtained particularly in the later period of the study with the increased dosage of the protocol regimen.