Concurrent concentrated chemoradiation therapy in squamous cell carcinoma of the esophagus: long term results of a national multicenter phase II study in 122 inoperable patients (FFCD 8803)
Jf. Seitz et al., Concurrent concentrated chemoradiation therapy in squamous cell carcinoma of the esophagus: long term results of a national multicenter phase II study in 122 inoperable patients (FFCD 8803), GASTRO CL B, 24(2), 2000, pp. 201-210
Objectives-Concomitant radiochemotherapy improves survival from inoperable
esophageal cancer compared to radiotherapy alone. Several regimens of radio
therapy (standard or concentrated split course radiotherapy) are used, howe
ver the optimum protocol remains to be determined The aim of this study was
to analyze the efficacy and tolerance of concentrated concomitant split co
urse radiochemotherapy. prognostic factors as well as those positively infl
uencing complete response were also studied.
Methods - This multicentric phase II trial looked at patients with histolog
ically proven, inoperable, squamous cell esophageal carcinoma without metas
tases or invasion of the tracheobronchial mucosa. Treatment included 3 cycl
es of chemotherapy by 5-FU continuous infusion (800 mg/m(2).d D1-D5, D22-D2
6, D43-D47) cisplatin (70 mg/m(2) D2, D23, D44) and radiotherapy 15 Gy/5d (
D1-D5, D22-26, D43-D47). Efficacy was analyzed by endoscopy, biopsy and com
puterized axial tomography during the 12(th) week of treatment.
Results - The trial included 122 patients from 21 centers (110 M and 12 F,
mean age 63.1 +/- 8.6 years, range 40 - 78). In accordance with the TNM-UIC
C classification (1978), 8 patients were classified stage I (T1 N0) 13 stag
e II (T2 N0), 100 stage III (T3 and/or N1) and stage was unknown in 1 patie
nt. Median follow-vp was 63 months. Treatment was complete in half of the p
atients. 5 premature deaths (4.1%) were recorded over the treatment period,
of which was directly linked to the toxicity of the the treatment. 16% of
patients showed at least one severe side-effect. 117 patients received all
3 cycles of the treatment 88 of them without delay, and all were evaluated.
58 (47.5% of the patients included) showed a complete response with a nega
tive biopsy, 36 (29.5%) showed a partial response, 13 (10.7%) were stable a
nd 10 (8.2%) showed progressive disease. The median duration of complete re
sponses wets 11.5 months. Symptomatically, dysphagia improved in 80% of the
the cases, performance status in 40%, and weight gain was observed in 30%
of the patients with weight loss. At evaluation, oral feeding was impossibl
e in 4 patients only and possible in 113 patients; however, endoscopic trea
tment of the dysphagia remained necessary in 28 patients. Median survival i
n the 122 patients included was 13.0 +/- 1.6 months and survival rates were
52.9, 29.8 and 12.1% at 1, 2 and 5 years, respectively. Three pretherapeut
ic prognostic factors influenced survival in a multivariate analysis: initi
al severe dysphagia (risk of premature death increased 3-fold in the first
year), circumferential extension and the differentiated nature of the tumor
(risk of death doubled regardless of the time delay). Factors influencing
a complete clinical response were on early tumor siege, a poorly differenci
ated tumor in patients older than 65, and no circumferential extension. The
risk of recurrence was 54.8% at 1 year in the 58 Patients with complete re
mission. Complete circumferential extension and a well or moderately differ
entiated tumour influenced recurrence.
Conclusion - This trial confirms the efficacy and good tolerance of concent
rated split course radiochemotherapy in patients with inoperable esophageal
cancer with a 5-year survival rate of 12%. This reinforces the need fbr a
comparative trial (split course irradiation vs standard irradiation) such a
s the one currently being conducted in France.