treating locally advanced rectal cancer with tas-102 chemotherapy plus neoadjuvant radiotherapy

Conditions: Rectal Cancer

Summary: the goal of this phase 2 trial is to evaluate a neoadjuvant treatment mode for locally advanced rectal cancer (larc), consisting of radiotherapy and concurrent trifluridine/tipiracil (tas-102). the main questions it aims to answer are: (i) whether tas-102 is effective in treating larc, when combined with radiotherapy; (ii) whether tas-102 is safe in combination with radiotherapy. participants will receive one cycle of tas-102 chemotherapy and neoadjuvant radiotherapy based on intensity-modulated technique. then the ones with a possibility of r0 resection will receive radical surgery followed by 6 cycles of adjuvant xelox (capecitabine plus oxaliplatin) chemotherapy.

the standard management recommended by the national comprehensive cancer network for locally advanced rectal cancer (larc) is neoadjuvant chemo-radiotherapy followed by surgery plus adjuvant chemotherapy or not. currently, the regimens of neoadjuvant chemotherapy are based on fluorouracil or capecitabine. the therapeutic effects of these regimens are satisfactory, with a pathological complete response (pcr) and 3-year disease-free survival (dfs) rate of 14% and 68%. addition of oxaliplatin has been proven to further improve the pcr and dfs rates, by the cao/aro/aio-04, fowarc and adore trials. however, the acute toxicities of fluorouracil and capecitabine remain as a concern. it was reported that the incidence of the grade 3/4 symptomatic toxicities brought by these two agents was nearly 15%. when combined with oxaliplatin, the incidence could rise to 25%. a special toxicity, hand-foot syndrome, was seen in 43-71% of the patients receiving capecitabine. it included blister, ulceration, numbness, pain and paresthesia, and seriously influenced the daily work and life of the patients. trifluridine/tipiracil (tas-102) is a new generation of cytotoxic agent whose therapeutic effects in metastatic colorectal cancer have been confirmed by a series of large-scale, multicenter, randomized controlled trials. and the latest tasco1 trial reported that tas-102 exhibited a trend to improve overall survival, compared to capecitabine. moreover, it could be well tolerated, with an incidence of grade 3/4 symptomatic toxicities of merely 1.5%. until now, there was few study focusing on combination of tas-102 and radiotherapy. this phase 2 trial intended to evaluate the therapeutic and adverse effects of tas-102 concurrently with neoadjuvant radiotherapy, in a small patient cohort with larc. the results might provide an effective and low-toxic choice which improves patients' experience of chemo-radiotherapy.

Eligibility criteria:
inclusion criteria: * pathologically diagnosed rectal adenocarcinoma via biopsy * pretreatment clinical tnm stage as t3-4n0m0 or t1-4n1-2m0 (uicc tnm staging classification, version 8) * tumor with proficient dna mismatch repair confirmed by immunohistochemical analysis * age between 18 and 75 years old * karnofsky performance score ≥ 70 * distance from tumor lower margin to anal verge \< 12 cm exclusion criteria: * inguinal lymph node metastasis * multiple primary colorectal cancer * complete obstruction or perforation * uncontrolled tuberculosis, aids or mental diseases * severe cardiac, renal, hepatic or hematopoietic dysfunctions unsuitable for chemotherapy or radiotherapy * prior history of other malignancies with 5 years, except cured cervical carcinoma in situ and skin basal cell carcinoma * prior history of rectal surgery, pelvic radiotherapy or chemotherapy * pregnant or lactating women * other situations for which the investigators consider a patient inappropriate to participate

Keywords: rectal cancer trifluridine/tipiracil radiotherapy