Prospective pilot study demonstrates high radiological response and manageable toxicity with neoadjuvant chemo-targeted therapy in KRAS wild-type rectal cancer, indicating feasible tumor downstaging.
AIM: to assess early efficacy and tolerability of preoperative chemotherapy combined with targeted therapy in patients with rectal cancer (RC). PATIENTS AND METHODS : a pilot prospective study including 22 RC patients with KRAS wild-type gene is ongoing from 2021. There are 13 (59.1%) females and 9 (40.9%) males. Stage II RC was diagnosed in 2 (9.1%) patients and stage III RC in 20 (90.9%) patients. All patients received 6 cycles of mFOLFOX 6 chemotherapy combined with cetuximab targeted therapy followed by surgery. After completion of surgical treatment, patients with T4 and/or N + received adjuvant chemotherapy for 6 months (taking into account the time of preoperative treatment). RESULTS: the completion rate of preoperative treatment was 90.9%, and a 15% reduction in drug dosages was required in 9.1% of patients. Adverse events were observed in 45.4% of patients. Grade III toxicity was noted in 13.6% of patients (neutropenia in 9.1% and skin rash in 4.5%). The clinical and radiological response to preoperative chemo-targeted therapy was 77.3%, including complete (9.1%) and partial (68.2%) tumor regression. All patients underwent radical surgery. The rate of postoperative complications was 13.6%. Grade I and grade IIIa complications (according to Сlavien-Dindo classification) were observed in 9.1% and 4.5% of cases. Pathological complete response (pCR, according to Mandard TRG 1) was achieved in 13.6% of patients, and good pathological response (TRG 1-2) was observed in 31.8% of patients. CONCLUSION : preoperative chemotherapy combined with targeted therapy in RC patients with the wild type of the KRAS gene has a pronounced damaging effect on the tumor, and an acceptable toxicity profile does not affect intraand postoperative period. The short-term outcomes have been found to be encouraging. The study is ongoing to analyze the survival of patients.
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Dobrodeev et al. (2025) studied this question.
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