Prospective evaluation of preoperative chemotherapy in resectable squamous cell carcinoma of the thoracic esophagus. Randomized trial of preoperative chemotherapy for squamous cell cancer of the esophagus. The Chirurgische Arbeitsgemeinschaft Fuer Onkologie der Deutschen Gesellschaft Fuer Chirurgie Study Group. Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. Induction chemotherapy in the treatment of patients with carcinoma of the esophagus. [A randomized clinical study of preoperative chemotherapy for esophageal carcinoma]. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagus: a prospective randomized trial. Randomized clinical trial of preoperative and postoperative adjuvant chemotherapy with cisplatin, vindesine, and bleomycin for carcinoma of the esophagus.
A prospective study was performed to clarify the surgical outcome of patients with esophageal carcinoma who would benefit from induction chemotherapy followed by surgery. Of 55 eligible patients, 42 (76.3%) agreed to randomization with either chemotherapy followed by surgery (n = 21) or surgery alone (n = 21). The other 13 refused. The chemotherapy consisted of cisplatin, 5-fluorouracil and leucovorin. All 55 patients underwent esophagectomy with two- or three-field resection, including two (3.6%) hospital mortalities. Of the 21 patients receiving chemotherapy, the response rate was 33.3% after the first course and 60% after the second course. A complete response was not obtained. Responders to the first course showed a prolonged survival, however time to treatment failure did not differ between patients treated with chemotherapy followed by surgery or surgery alone. This chemotherapy offered a worse surgical outcome for patients with pretreatment diagnosis of T3. Multivariate analysis identified a partial response to the first course of chemotherapy to be a favorable prognostic indicator. Preoperative chemotherapy does not give a survival benefit over surgery alone for patients with advanced tumor (T3). Initial response to the first dose of chemotherapy is deemed to be a prognostic factor for patients with less advanced tumor (T1/T2). Of 77 patients with potentially resectable squamous cell carcinoma of the esophagus who were asked to participate in a phase III trial of treatment with either immediate surgery (n = 24) or surgery plus preoperative chemotherapy (n = 22), only 46 agreed to randomization. A priori, 13 patients chose chemotherapy before surgery and 18 patients chose surgery only. The complete chemotherapy program consisted of three cycles with fluorouracil, 1 g/m2 per day for 5 days, and cisplatin, 20 mg/m2 per day for 5 days. The response rate to chemotherapy was 50% (17 of 34 patients). Side effects of therapy were higher than expected based on results of previous phase II studies. Two drug-related deaths were observed. The resectability rate for patients in the surgery only group was 79% (33 of 42 patients) compared with 70% (19 of 27 patients) for patients receiving chemotherapy. The postoperative rates of septic complications (41% [11 of 27 patients] vs 26% [11 of 42 patients]) and respiratory disorders (48% [13 of 27 patients] vs 31% [13 of 42 patients]) were higher for patients with preoperative chemotherapy than for those treated with surgery only. Surgery-related mortality was increased in the chemotherapy group (19% [five of 27 patients]) compared with the surgery only group (10% [four of 42 patients]). Patients responding to preoperative chemotherapy had prolonged survival (median, 13 months) compared with nonresponders (median, 5 months), but the median survival for the chemotherapy group and the surgery only group was identical (10 months). We conclude that the preoperative chemotherapy regime used in this multi-institutional trial neither influences resectability nor increases the overall survival of patients with localized esophageal cancer. However, preoperative chemotherapy is associated with considerable side effects and a high postoperative mortality rate. In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival. A prospective randomized phase III trial was carried out at Songklanagarind Hospital from August 1988 to December 1990. The objectives of the study were to evaluate the effect of chemotherapy regimen in squamous cell carcinoma of the esophagus and to determine whether induction chemotherapy improves symptom-free period and survival in these patients compared to surgical treatment alone. Twenty-four patients were randomized to receive 2 cycles of chemotherapy, cis-platinum 100 mg/m2 intravenously on day 1, bleomycin 10 mg/m2 loading dose on day 3, followed by 10 mg/m2/day continuous intravenous infusion on days 4 through 7, and vinblastine 3 mg/m2 given intravenously on days 1, 8, 15, 22. The cycle was repeated on day 29. Fifteen patients completed 2 courses of chemotherapy and among these, 2 patients had a complete clinical response (13%), 6 (40%) had a partial response, and 7 patients (47%) had no response. Four patients died during chemotherapy treatment. Grade 3 hematologic toxicity (ECOG criteria) was observed in 47% (7/15) of patients. Twenty-two patients were randomized to conventional treatment (surgery alone). Median survival time was 17 months in both groups. However, early survival appeared to be better in the control group. Kaplan-Meier survivals at 6 months were 69% and 89% and at 3 years were 31% and 36% for the induction chemotherapy group and control group, respectively. The survival time differences were not statistically significant (P = 0.186). These findings demonstrate that although this chemotherapy regimen had some effect on squamous cell carcinoma of esophagus, it did not improve survival. On the contrary, survival seems to be better in the control group. The 6-month survival discrepancy between both groups might be due to the poor nutritional status of our patients, who may better tolerate smaller dosages of chemotherapy. To evaluate the effect of preoperative chemotherapy on the prognosis of stage II or III patients with esophageal carcinoma.
                From February 1991 to June 1994, 50 patients with stage II, III esophageal carcinoma were treated with preoperative combination (CDDP) chemotherapy and compared with 50 patients received operation alone.
                The 5-year survival rate of the operation group and preoperative chemotherapy group was 32% and 46%, respectively. The difference was statistically significant.
                Preoperative chemotherapy improves survival of surgically treated esophageal cancer patients. We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer.
                Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival.
                Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites.
                Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus. Surgery is the standard treatment for patients with resectable esophageal carcinoma, but the long term prognosis of these patients is unsatisfactory. Some randomized trials of preoperative chemotherapy suggest that the prognosis of patients who respond may be improved.
                This randomized, controlled trial compared patients with clinically resectable esophageal epidermoid carcinoma who underwent surgery alone (Arm A) with those who received preoperative chemotherapy (Arm B). Overall survival and the prognostic impact of major response to chemotherapy were analyzed. Forty-eight patients were enrolled in each arm. Chemotherapy consisted of two or three cycles of cisplatin (100 mg/m2 on Day 1) and 5- fluorouracil (1000 mg/m2 per day continuous infusion on Days 1-5). In both study arms, transthoracic esophagectomy plus two-field lymphadenectomy was performed. The two groups were comparable in terms of patient characteristics.
                Forty-seven patients were evaluable in each arm. The curative resection rate was 74.4% (35 of 47 patients) in Arm A and 78.7% (37 of 47 patients) in Arm B. Treatment-related mortality was 4.2% in both arms. The response rate to preoperative chemotherapy was 40% (19 of 47 patients), including 6 patients (12.8%) who achieved a pathologic complete responses. Overall survival was not improved significantly. The 19 patients in Arm B who responded to chemotherapy and underwent curative resection had significantly better 3-year and 5-year survival rates (74% and 60%, respectively) compared with both nonresponders (24% and 12%, respectively; P = 0.0002) and patients in Arm A who underwent complete resection (46% and 26%, respectively; P = 0.01): Patients who achieved a pathologic complete response (P = 0.01), but not those who achieved a partial response (P = 0.2), had significantly improved survival.
                Patients with resectable esophageal carcinoma who underwent preoperative chemotherapy and obtained a pathologic complete response had a significantly improved long term survival. Major efforts should be undertaken to identify patients before neoadjuvant treatments who are likely to respond.
                Copyright 2001 American Cancer Society. This study investigated the role of preoperative chemotherapy in squamous cell cancer of the esophagus.
                A prospective randomized trial was undertaken in 147 patients: 74 received preoperative chemotherapy comprising cisplatin and 5-fluorouracil and 73 had surgical therapy alone. End points were cancer and therapy-related deaths.
                Sixty-six patients (89%) in the chemotherapy group underwent resection compared with 69 (95%) in the control group (p = not significant). Of the 60 patients who had resection after completing the chemotherapy program, 35 (58%) had a significant response, of whom four (6.7%) had a complete pathologic response. Postoperative mortality rates were 8.3% and 8.7% in the chemotherapy and control groups, respectively (p = not significant). Significant downstaging was evident with chemotherapy; curative resections were possible in 67% of these patients compared with 35% in the control group (p = 0.0003). T3 and T4 tumors were found in 67% and 91% of the chemotherapy and control groups, respectively (p = 0.0002). The respective figures for N1 disease were 70% and 88% (p = 0.009). An intent-to-treat analysis of survival showed no significant difference between the two groups. Median survivals were 16.8 and 13 months, respectively (p = 0.17). Of those who completed the chemotherapy and resection, responders fared better than control patients. Median survivals were 42.2 months and 13.8 months, respectively (p = 0.003). Median survival (8.3 months) was worse for nonresponders than for control patients (p = 0.03). The recurrence pattern suggested a significant reduction in locoregional disease with chemotherapy.
                Preoperative chemotherapy was safe and resulted in significant downstaging and an increased likelihood of curative resection. Survival was not better than that in the surgery-alone group, but responders did fare better than nonresponders. Thirty-nine patients with potentially resectable cancer of the middle or lower esophagus who had not previously been treated were randomly assigned to receive either immediate operation (n = 20) or operation plus preoperative and postoperative therapy with cisplatin, vindesine, and bleomycin (n = 19). Patients were stratified by tumor size and location and by sex, with no significant differences appearing between the two treatment groups. Median follow-up for both groups was 30 months. The preoperative response rate to chemotherapy was 47%. The postoperative complication rate for patients in the operation-only group was 47%; it was 29% for patients receiving chemotherapy. The overall resectability rates were similar for the two groups. Patients responding to chemotherapy preoperatively had significantly prolonged survival (median greater than 20 months) when compared with either nonresponders (median 6.2 months) or patients receiving only operation (median 8.6 months). A highly significant correlation was noted between a weight loss of less than 10% and response to chemotherapy, which suggested that responses occurred in patients with less advanced disease. We conclude that preoperative and postoperative cisplatin, vindesine, and bleomycin chemotherapy has acceptable toxicity and does not increase the incidence of postoperative complications. The natural history of epidermoid carcinoma of the esophagus is altered and overall survival is prolonged for patients responding to preoperative chemotherapy. Potential responding patients can be identified by the degree of preoperative weight loss.
In summary, preoperative chemotherapy plus surgery may offer a survival advantage compared to surgery alone for resectable thoracic esophageal cancer, but the evidence is inconclusive. There is some evidence of toxicity and preoperative mortality associated with chemotherapy.