5-fluorouracil and cisplatin therapy after palliative surgical resection of squamous cell carcinoma of the esophagus - A multicenter randomized trial

Background The curative rate of surgical resection of squamous cell carcinoma of the esophagus is low. Reports on the efficacy of preoperative and postoperative chemotherapy are conflicting or have included limited disease or radical surgery alone. Objective The authors' objective was to study the results of chemotherapy on the duration and quality of survival in patients who have undergone palliative surgical resection for esophageal squamous cell carcinoma. Patients and Methods Of 124 patients with histologically proven esophageal squamous cell carcinoma situated more than 5 cm from the upper end of the esophagus, 4 patients were withdrawn for failure to comply with the protocol. The remaining 120 patients, 116 males and 4 females (mean age, 57 +/- 9 years), were randomly assigned to either a control group who were to receive no chemotherapy (68 patients) or to a group who were to be treated with chemotherapy (52 patients). Patients were subdivided into two strata as follows: (1) stratum I, complete resection of the tumor with lymph node involvement (62 patients) and (2) stratum II, incomplete resection leaving macroscopic tumor tissue in situ or with metastases. Noninclusion criteria were histologically proven tracheobronchial involvement, esotracheal fistula, major alteration of general health status (Karnofsky score 30% of parenchyma) hepatic metastasis, peritoneal carcinomatosis, associated or previously treated upper airway cancer, or, conversely, complete resection of tumor without lymph node involvement. Chemotherapy was given in 5-day courses, every 28 days, with a maximum of 8 courses. Cisplatin was administered either as a single dose of 100 mg/m(2) at the beginning of the course or as 20 mg/m(2)/day for 5 days given over 3 hours. 5-Fluorouracil (5-FU) (100mg/m(2)/day) was infused over 24 hours for 5 days. The duration of treatment ranged from 6 to 8 months. The main aim was to establish median survival and actuarial survival curves. The subsidiary aim was to evaluate quality of survival as judged by complications due to treatment and the duration of autonomous oral feeding, that is, without palliative endoscopic treatment. No difference in survival was noted between the two groups, overall (median, 14 months), or between the strata. Conversely, significantly more patients in the treated group had hematologic, neurologic, and renal complications compared with the control group, Four patients died of complications of chemotherapy. The duration of autonomous oral alimentation was exactly the same in both groups (median, 121/2 months). Conclusion The results oi this study suggest that 5-FU and cisplatin are not useful for patients with squamous cell carcinoma of the esophagus who have not undergone curative resection

5-fluorouracil and cisplatin as palliative treatment of advanced oesophageal squamous cell carcinoma: A multicentre randomised controlled trial

Objective: To compare chemotherapy with no chemotherapy as palliative treatment for oesophageal squamous cell carcinoma. Design: Randomised study. Setting: Multicentre trial in France. Subjects: Of 161 patients with histologically confirmed oesophageal squamous cell carcinoma located more than 5 cm from the mouth of the oesophagus, five were withdrawn because of protocol violation. The remaining 156 patients, 149 men and 7 women, mean (SD) age 58 (9) years range 36 to 77, were randomly allocated to either a control group without chemotherapy (n = 84) or a group treated by chemotherapy (n = 72). Patients were divided into four strata: I = complete resection of the tumour but with lymph node involvement (n = 62); II = incomplete resection of tumour leaving gross tumour behind (n = 58); III = no resection because of local or regional invasion (n = 22); and IV = no resection because of distant metastasis (n = 14). Exclusion criteria were histologically confirmed tracheobronchial involvement, oesophagotracheal fistula, Karnosky score < 50, cerebral metastases, or hepatic metastases occupying more than 30% of the liver, peritoneal carcinomatosis, associated or previously treated ear-nose-throat carcinoma, or complete resection of tumour without lymph node involvement. Interventions: 5 fluorouracil (5FU) and cisplatin (CDDP) were given in 5-day courses, once every 28 days, for a maximum of eight cycles. 5 FU, 1 g/m 2, was infused for 24 hours after a water overload, during five days. Cisplatin was given either in one dose of 100 mg/m 2 at the beginning of the cycle or 20 mg/m 2/day over three hours for five days. Duration of treatment ranged from 6-8 months. Outcome measures: Median and actuarial survival. The subsidiary endpoint was quality of survival judged by complications of treatment, swallowing disorders, and the duration of ability to feed normally. Results: There was no difference in survival, either overall (median = 12 months) or in any of the strata. There were however significantly more patients with neurological (p < 0.003), haematological (p < 0.0001), and renal (p < 0.0002) complications in the treated group compared with the control group. Four patients (6%) died of complications of chemotherapy. The course of swallowing disorders did not differ between the two groups. The duration of autonomous oral feeding was exactly the same in both groups (median = 10.5 months). Conclusion: The results suggest that 5FU and CDDP do not help in patients with squamous cell carcinoma of the oesophagus whether or not the tumour has been resected