Tadashi Sugita

CONCURRENT RADIOTHERAPY AND CHEMOTHERAPY WITH PROTRACTED CONTINUOUS INFUSION OF 5-FLUOROURACIL IN INOPERABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

PURPOSE The feasibility of a concurrent chemoradiotherapeutic protocol for patients with inoperable esophageal squamous cell carcinoma was tested. METHODS AND MATERIALS Concurrent chemoradiotherapy using protracted low-dose continuous infusions of five-fluorouracil (5-FU; 250-300 mg/m2/24 h) and standard external beam irradiation was given to 28 patients with inoperable esophageal squamous cell carcinoma between November 1991 and June 1993. RESULTS For 25 patients receiving a total dose of > or = 60 Gy and concurrent 5-FU infusion for more than 5 weeks, the complete response rate was 52%. Local progression-free rate in this chemoradiotherapy group was significantly higher than the historical controls treated by radiotherapy alone (p < 0.05). A multivariate analysis revealed the treatment scheme (concomitant chemoradiotherapy vs. radiotherapy alone) to be a significant factor in local control (p < 0.01). Swallowing pain (39%), anorexia (39%), and nausea (32%) were the most frequent early reactions. Serious late radiation complications have not been observed. CONCLUSION The concurrent chemoradiotherapy using protracted low-dose continuous infusion of 5-FU and standard radiotherapy is an effective and safe method to obtain a local control in inoperable esophageal squamous cell carcinoma.

Risk factors for enlargement of cardiac silhouette on chest radiography after radiotherapy for esophageal cancer.

PurposeTo evaluate the incidence and risk factors of enlargement of cardiac silhouette on chest radiographs after radiotherapy for esophageal cancer.Materials and methodsWe analyzed 67 patients with esophageal cancer who received external beam radiation therapy with a total dose of ≥50 Gy and were followed for ≥6 months. Sixteen patients received radiation alone, and the remaining 51 received chemoradiotherapy. The difference between the cardiothoracic ratio (CTR) on the pretreatment chest radiograph and that on the posttreatment radiograph with maximum cardiac silhouette for each patient was used for the analysis.ResultsThe average maximum increase in CTR for the entire group was 4.5%, which was statistically significant. Only the area of the cardiac silhouette in the initial radiation field was a significant risk factor for enlargement of the cardiac silhouette. Pericardial effusions were observed in all patients who underwent computed tomography with severe enlargement of the cardiac silhouette.ConclusionThe CTR value significantly increased after radiotherapy for esophageal cancer. Radiation-induced pericardial effusion may be the main cause of enlargement of the cardiac silhouette. The irradiated cardiac area was the only significant risk factor for enlargement of the cardiac silhouette; the use of chemotherapy was not.

Concurrent chemoradiotherapy using low-dose continuous infusion of 5-fluorouracil for postoperative regional lymph node recurrence of esophageal squamous cell carcinoma

BackgroundRadiotherapy plays an important role in salvaging patients who suffer locoregional recurrence; however, it displays poor prognosis. Because concurrent chemoradiotherapy offers superior treatment results compared to radiotherapy alone in patients with localized esophageal cancer, to improve survival rates, we treated patients displaying postoperative regional lymph node recurrence of esophageal squamous cell carcinoma using radiotherapy combined with protracted low-dose continuous infusion of 5-fluorouracil (5-FU).MethodsBetween January 1992 and December 2001, 14 patients with postoperative regional lymph node recurrence of esophageal squamous cell carcinoma were treated with concurrent chemoradiotherapy. Radiotherapy was delivered at 1.8–2.0 Gy/day, for a total dose of 56–70 Gy (median, 60 Gy). Chemotherapy was administered 5 days/week as continuous infusion of 5-FU (250–300 mg/m2) for at least 5 weeks. Median follow-up time was 27 months.ResultsTwelve patients demonstrated partial response, and 2 patients displayed stable disease. Response rate was therefore 86% (12/14). In-field recurrence occurred in 3 patients. Involved lymph nodes that recurred in the irradiation field were ≥40 mm in maximum diameter and invaded into the surrounding normal tissues. Local progression-free rate at 2 years was 72%. As an initial failure, 6 patients displayed out-field recurrence. Disease progression-free rate at 2 years was 42%. Overall survival rates at 1 and 2 years were 85% and 57%, respectively.ConclusionsConcurrent chemoradiotherapy using low-dose continuous infusion of 5-FU was effective for patients with postoperative regional lymph node recurrence of esophageal squamous cell carcinoma. Close follow-up is crucial, and further investigation is required to prevent out-field recurrence.

Neoadjuvant chemotherapy followed by concurrent chemotherapy and radiotherapy for locally advanced esophageal carcinoma with bulky upper abdominal lymphadenopathy. Case report.

A 60-year old male patient who had locally advanced esophageal carcinoma with bulky upper abdominal lymphadenopathy underwent neoadjuvant chemotherapy consisting of 5-fluorouracil (5-FU) and cisplatin (CDDP), followed by concurrent radiotherapy and chemotherapy using protracted low-dose continuous infusion of 5-FU and CDDP. The treatment brought about complete remission in the primary lesion and good partial remission in the upper abdominal lymphadenopathy. He subsequently underwent trans-hiatal esophagectomy after one cycle of adjuvant chemotherapy because local recurrence was suspected. Histopathologic study of the resected specimen demonstrated no malignant tissue in the primary lesion and the lymph nodes. The patient is still alive and disease-free at 26+ months. This result suggests that neoadjuvant chemotherapy followed by concomitant chemotherapy and radiotherapy for patients who have locally advanced squamous cell carcinoma of the esophagus with intensive abdominal lymphadenopathy may offer some chance for sterilization of local and regional metastases and longer survival.

Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan

OBJECTIVE Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese. METHODS Patients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II-IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70mg/m2 for level 0, 80mg/m2 for level 1, and 100mg/m2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200mg/m2, response rate, and incidences of adverse events. RESULTS A CDDP dose of 100mg/m2 was the MTD for phase I, and the recommended dose for phase II was 80 mg/m2. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200mg/m2, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event. CONCLUSION The present phase I study indicated that a CDDP dose of 80mg/m2 is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80mg/m2 as compared with a dose of 100mg/m2, and a dose of 80mg/m2 is therefore recommended in CCRT for the Japanese. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification No. UMIN000010369).