Intense Therapy in Patients with Locally Advanced Esophageal Cancer beyond Hope for Surgical Cure: A Prospective, Multicenter Phase II Trial of the Swiss Group for Clinical Cancer Research (SAKK 76/02)

Abstract

Background: There is no standard treatment for patients with locally advanced esophageal carcinoma without systemic metastasis in whom surgery is no longer considered a reasonable option. Patients and Methods: Patients with cervical esophageal tumors, locally very advanced stage (T4 and/or M1a) or locally advanced (T3 and/or N+) with comorbidities were included. Therapy: 2 cycles of induction chemotherapy (cisplatin and docetaxel, both 75 mg/m2 3-weekly) followed by chemoradiation therapy (CRT) comprising a total radiation dose of 59.4 Gy together with docetaxel 15 mg/m² and cisplatin 25 mg/m² (5 weekly doses). Primary endpoint: Histologically proven freedom from local failure 6 months after CRT completion. Results: 21 patients were included: 12 had locally very advanced tumors, 3 had cervical esophagus tumors, and 6 were medically unfit for surgery. 18 patients completed therapy per protocol. Grade 3/4 toxicities during CRT were thrombopenia (10%) and dysphagia (15%). 1 patient died due to herpes simplex infection. The primary endpoint was achieved by 4 patients, 6 were alive after median follow-up of 34 months, and median survival was 16 months. Most patients experienced lasting improvement of dysphagia following induction chemotherapy. Conclusions: This regimen is feasible, showed clinically meaningful, long-lasting improvements in quality of life and resulted in long-term survival in 29% of the patients.

Prospective, open, multi-centre phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and oxaliplatin in patients with adenocarcinoma of the oesophagogastric junction

“…Efficacy endpoints should be confirmed in larger clinical trials, preferably including newer biological agents and again preferably focusing on specific esophagogastric sites to omit different possible post-operative morbidity and mortality rates [26,27]. …”

Outcomes of Definitive Chemoradiotherapy for Stage Iva (T4b Vs N4) Esophageal Cancer Based on the Japanese Classification System: A Retrospective Single-center Study 

“…Moreover, if recurrence occurs in an area that was prophylactically irradiated using a dose of approximately 40 Gy, it would not be feasible to perform de nitive radiotherapy at a dose of > 50 Gy at the same area, which may preclude salvage CRT for the recurrent lesion and worsen local control and OS [33]. Neo-adjuvant CRT for esophageal cancer provides a pathological CR rate of only 23-68% when various chemotherapy regimens were combined with a radiation dose of approximately 40 Gy [34][35][36][37][38][39]. Thus, a prophylactic dose of 40 Gy may be insu cient to achieve local control and might preclude adequate salvage CRT if the patient experiences local lymph node recurrence.…”

Outcomes of Definitive Chemoradiotherapy for Stage IVa (T4b vs. N4) Esophageal Squamous Cell Carcinoma Based on the Japanese Classification System: A Retrospective Single-Center Study

“…Moreover, if recurrence occurs in an area that was prophylactically irradiated using a dose of approximately 40 Gy, it would not be feasible to perform definitive radiotherapy at a dose of >50 Gy in the same area, which may preclude salvaged CRT for the recurrent lesion and may worsen local control and OS [26]. Neo-adjuvant CRT for esophageal cancer provides a pathological CR rate of only 23-68% when various chemotherapy regimens were combined with a radiation dose of approximately 40 Gy [27][28][29][30][31][32]. Thus, a prophylactic dose of 40 Gy for the ENI area in definitive CRT may be insufficient to achieve local control and might preclude adequate salvaged CRT if the patient experiences local lymph node recurrence.…”