Prospective randomised study of split-course radiotherapy versus cisplatin plus split-course radiotherapy in inoperable squamous cell carcinoma of the oesophagus
Introduction
The prognosis of patients with oesophageal cancer is poor, even after a curative resection. Most of the patients die from distant metastases which indicates that from the first clinical symptoms of the disease it is systemic in most of the patients. This fact ensures strong support for combined treatment modalities that expect to have a maximal local effect and to eradicate distant micrometastases in order to improve survival. The Gastro Intestinal Tract Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC) initiated in 1983 a phase III controlled clinical trial of irradiation versus irradiation and cisplatin (CDDP) in patients with irresectable squamous cell carcinoma of the oesophagus (EORTC 40831). In the early eighties, results from phase II trials showed that CDDP and bleomycin were among the most active drugs against oesophageal carcinomas. The group chose to test CDDP as a single agent in combination with irradiation because of the risk of pulmonary toxicity associated with the use of bleomycin which might be aggravated with concomitant mediastinal irradiation and because there was no clear demonstration of a benefit with polychemotherapy. At that time, the total dose of irradiation was given on an inpatient basis due to the poor tolerance by the majority of the patients. An admission of more than 5 weeks was considered to be too long for patients with an expected short survival. To prevent a long hospital stay, it was therefore decided to introduce a split-course scheme, a method which was described for patients with bronchogenic carcinoma [1], head and neck cancer [2] and in the early seventies for oesophagus carcinoma [3].
Section snippets
Patients
All patients were required to have squamous cell carcinoma, be aged under 70 years, have had no prior chemotherapy, a performance status of World Health Organization (WHO) 0–2; any T1–3 lesion according to the 1979 International Union Against Cancer (UICC) classification (T1: tumour ⩽5 cm, T2: tumour >5 cm, T3: extra oesophageal spread), but without superficial (cervical) lymph node metastases or distant metastases (infradiaphragmatic lymph node involvement was not a reason for exclusion
Results
From December 1983 to February 1989, 221 patients from 11 institutions were randomised (Fig. 1). Then it was decided to close the trial because of the low accrual rate. There were 111 patients in the radiotherapy arm (A) and 110 in the radiotherapy+CDDP arm (B). All patients were evaluated and 18 (8%) were considered ineligible (10 in A and 8 in B). The reasons for ineligibility were inadequate staging (15), poor physical condition (2) and prior treatment (1).
Except for clinical stage at entry,
Discussion
CDDP is a common component of combination chemotherapy for squamous cell carcinoma of the oesophagus, although it is not known whether CDDP is really an essential component of combination chemotherapy for oesophageal cancer 7, 8. CDDP-containing combinations may, however, give a response rate of almost 50%. In these combinations toxic effects are considerable, and although tolerable, these effects may have a very negative effect on the remaining months of the patient's life. CDDP as a single
Acknowledgements
This publication was supported by grant number 2U10 CA11488-13 through 5U CA1488-29 from the National Cancer Institute (Bethesda, MD, USA) Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute.
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A network meta-analysis of the treatments for esophageal squamous cell carcinoma in terms of survival
2018, Critical Reviews in Oncology/HematologyChemoradiation for Esophageal Cancer
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2012, Surgical Clinics of North AmericaCitation Excerpt :Early results showing improved local control and survival with CRT led to randomized controlled trials comparing RT alone with concurrent CRT.34–38,48–51 Most of these trials showed a survival benefit to concurrent CRT, but most of them did not use modern chemotherapy regimens or used split-course RT.34–37,48–51 Several other randomized trials investigated the use of sequential chemotherapy and RT for locally advanced esophageal cancer and found no benefit in local control or survival but did report increased toxicity.52–54 Radiation Therapy Oncology Group (RTOG) 8501 compared RT alone (64 Gy) with CRT (50 Gy with 4 cycles of concurrent and adjuvant cisplatin and 5-FU) and revealed a 5-year overall survival benefit to CRT of 26% compared with 0%.37,38
Randomized Clinical Trials in Esophageal Carcinoma
2010, Surgical Oncology Clinics of North AmericaCitation Excerpt :Furthermore, given that the accepted standard of care at the time of patient accrual for these studies was CRT, it is difficult to justify the presence of an RT-only arm in three of the four studies. Likewise, when chemotherapy was included it was either as single agent48,50 or the doses were too low.51 In none of theses studies did the clinical staging include a PET scan or EUS, making comparisons between groups and studies difficult.
A Phase I/II Study to Evaluate the Toxicity and Efficacy of Accelerated Fractionation Radiotherapy for the Palliation of Dysphagia from Carcinoma of the Oesophagus
2008, Clinical OncologyCitation Excerpt :In a phase II trial by Hayter et al.[15], where a moderate dose of radiotherapy, 30 Gy in 10 fractions, was combined with 5-fluorouracil and cisplatin, a 68% complete response rate with a low toxicity profile suggested that further study of modest-dose chemotherapy and radiotherapy is warranted. Existing randomised trials comparing chemotherapy and conventional radiotherapy with radiotherapy have focused predominantly on survival in the high-dose curative setting [36–43] with limited or no significant advantage for dysphagia relief in this setting. The paucity of randomised trials to address the relative effectiveness of different radiotherapeutic approaches for the palliation of dysphagia has contributed to the significant heterogeneity in clinical practice.