5FU-leucovorin combination improves treatment outcomes in LARC
The addition of a 4-week chemotherapy regimen comprising 5-fluorouracil (5FU) and leucovorin administered during the resting period between preoperative chemoradiotherapy (CRT) and surgery improves tumour downstaging and survival rates in individuals with locally advanced rectal cancer (LARC), according to a new study.
Twenty-three patients with LARC (median age 59 years, 65.2 percent male, 82.6 percent stage III) received standard preoperative CRT for 6 weeks (RT to the entire pelvis at a total dose of 50.4 Gy of radiation 5 days/week plus concurrent 5FU or capecitabine). Following this, participants received an additional regimen comprising two cycles of 5FU and leucovorin (5FU bolus 400 mg/m2 and leucovorin 200 mg/m2 on day 1 and 5FU infusion 2,400 mg/m2 for 46 hours every 2 weeks). Surgery was performed 2–4 weeks following completion of the additional chemotherapy regimen. Median follow-up duration was 42.0 months. [J Cancer 2019;10:186-191]
Tumour downstaging was observed in 65.2 percent of participants, while pathologic complete remission was observed in 21.7 percent. T and N downstaging were observed in 69.6 percent and 60.9 percent, respectively.
At 4 years, disease-free survival (DFS) and overall survival (OS) rates were 73.9 percent and 90.9 percent, respectively. DFS and OS rates were significantly improved among participants who had tumour downstaging vs those who did not (100 percent vs 25 percent; p<0.001 [DFS] and 100 percent vs 71.4 percent; p=0.031 [OS]).
Tumour response to preoperative CRT appears to be an important prognostic factor for local tumour control and survival, hence the importance of establishing strategies aimed at downstaging tumours, noted the researchers. Evidence shows excellent survival benefits in individuals who have exhibited tumour downstaging following preoperative CRT, [World J Surg 2012;36:675-683; Ann Surg Oncol 2012;19:2822-2832] with a reported downstaging rate of 65–85 percent. [Int J Radiat Oncol Biol Phys 2003;57:84-89; J Clin Oncol 2009;27:5124-5130]
“An increased tumour downstaging rate may not only change definitive surgery strategies for anal preservation but also impact the survival rate,” said the researchers. “Studies have demonstrated that the final pathologic stage remains the most significant prognostic factor in rectal cancer. Therefore, high tumour regression has been a significant goal in preoperative CRT for rectal cancer.”
Preoperative CRT is currently the standard treatment modality for LARC due to organ preservation, increased local control, and less toxicity, noted the researchers. However, up to 30 percent of recipients reportedly had distant metastasis, and the survival benefit of preoperative CRT remains to be established. [N Engl J Med 2004;351:1731-1740]
“[Our findings reveal that] additional chemotherapy … increased tumour downstaging and represented a more effective sphincter-saving resection through a potential antitumour effect,” said the researchers.
However, the findings should be interpreted with caution given the retrospective nature and single-centre design of the study, noted the researchers. Further randomized trials using a large population are warranted to substantiate the findings and arrive at more definitive conclusions, they added.