Preoperative sequential short-term radiotherapy plus chemotherapy can induce complete remission in T3N2 rectal cancer

To the editor: In rectal cancer, preoperative short-term radiotherapy with 25 Gy administered within one week leads to significant reduction of local recurrences but no down staging because surgery is generally performed within only a few days [1 /3]. For the same reason co-administration of systemic chemotherapy seems to make no sense and has not been attempted. Sequential use of both treatment modalities followed by surgery at a later time point, however, might have the same ‘‘antitumour potential’’ as preoperative long-term radiochemotherapy, today’s probably optimal treatment choice in patients with locally advanced rectal cancer [4]. The present report describes the successful use of this novel therapeutic concept in two patients with MRI-staged T3N2 rectal cancer (located at 4 cm and 7 cm from the anal verge without distant metastases) who attended our clinic in May and July 2004. Conventional preoperative long-term radiochemotherapy was offered to them routinely. Because of personal/geographical reasons as well as financial needs, both refused this treatment strategy; they wanted to continue regular work and attend the clinic as seldom as possible. After extensive information and discussion about possible alternative treatment options, it was decided to combine short-term radiotherapy immediately followed by dose-intensified capecitabine /oxaliplatin, a combination regimen that has shown an encouraging therapeutic index in patients with metastatic colorectal cancer [5]. Both patients consented in writing to undergo this hitherto untested combination of two treatments that have been studied in different settings in this disease. Prior to therapy, a full diagnostic workup including routine laboratory examinations, rectoscopy with biopsy, colonoscopy, thoracic plus abdominal CT, and pelvic MRI was performed. Radiotherapy was designed on the basis of a planning computed tomography with three fields covering the entire mesorectum including the tumour and lymph-nodes with a 1 cm safety margin [6]. The whole anal canal was included in the first patient, but not in the second. Single doses of 5 Gy to be administered daily to a total dose of 25 Gy were prescribed at the ICRU point. After completion of radiotherapy, chemotherapy was started on Monday of the following week. Oxaliplatin 85 mg/m was administered iv on days one and 15 with usual antiemetic premedication (5-HT3 antagonist /dexamethasone), and capecitabine 3500 mg/m was given orally in two divided doses from days one to seven and 15 to 21 as previously described [5]. Treatment was repeated every four weeks for three cycles. A complete restaging with thoracic and abdominal CTand pelvic MRI was scheduled thereafter, before surgery. The first patient, a 55 year-old male, presented with about seven fecal discharges per day, permanent painful urge, incontinence for fluid stools, and the feeling of pressure at micturition. Otherwise he was in very good general condition. Upon diagnostic workup, a 7 cm long rectal cancer with infiltration of the anal canal, infiltration of perirectal tissue and multiple suspicious lymph nodes (T3N2) was found upon MRI. There was no evidence of distant