Oxaliplatin in the perioperative, multimodal treatment (preoperative chemoradiotherapy, TME surgery and postoperative chemotherapy) of rectal cancer - a monocentric analysis -
by Beate Michels née Skubich
English
Due to conflicting study results, the use of oxaliplatin (OX) in perioperative multimodal treatment (MMT) for locally advanced adenocarcinoma of the rectum (LARC; clinically staged as cUICC stages II or III) is not recommended in national S3 guidelines "ColoRectal Carcinoma" (2019). Preoperative chemoradiotherapy (CRT: RT with 50.4 Gray combined with 5-fluorouracil (5-FU)), total mesorectal excision (TME) and adjuvant chemotherapy (CTx) with 5-FU continues to be considered as standard.
Between 07/2006 to 06/2016, a total of 177 LARC patients (55 w, 122 m; median age: 63 years) was treated at the university medical center of Göttingen (UMG) according to clinical trial protocols. Feasibility, toxicity (NCI-CTCAE criteria, version 4.03), and compliance to MMT (+/- OX) were investigated as well as treatment efficacy. Patients with cUICC stages II (4%), III (91%) and IV (5%), all localized < 12 cm above anal verge, were divided into cohort A (n=64, control: CRT + TME + adCTx (5-FU), B (n=63, intensified MMT: CRT+OX + TME + adCTx (FOLFOX) and C (n=50, total neoadjuvant treatment, TNT: CRT+OX + 3 applications of FOLFOX + TME).
In 98% RT and 95% CTx, the planned preoperative CRT could be administered (5% dose reduction). The amount of toxicity ≥ CTC-grade 3 was < 5%. For patients of cohorts A and B, postoperative adCTx was associated with low rates of toxicity (≥ CTC-grade 3: < 8%) and resulted in patient`s compliance of 77% (23% dose reduction). After surgery pathological control of specimen revealed optimal, moderate or poor quality of TME in 79%, 18% and 3% (according to MERCURY criteria), respectively. Sphincter-saving low anterior resections were performed in 71%. R0- and negative CRM-status (≥ 2 mm resection margin without cancer cells) as well as MMT-induced shrinkage in tumor extent (ypTE: ≤ 25 mm) were achieved in 96%, 92% and > 50%, respectively. Postsurgical staging revealed stages ypUICC-0 to -IV in 14.5%, 23.1%, 27.7%, 24.9% and 9.6%, respectively. During median follow-up of 73 months, distant metastases were diagnosed in 31.3% and local recurrences in 5.4% of patients. Univariate analyses showed differences in DFS for MMT-induced tumor regression (p = 0.001), ypCRM (p = 0.002) and ypTE (p = 0.023) status as well as in ypUICC stages (p < 0.0009). In multivariate CSS analysis (forest plot), ≤ ypUICC stages II had longer CSS (p = 0.007; HR: 0.31; 95% CI: 0.14-0.73).
The use of OX in perioperative MMT is safe, easy to apply and leads to strong early tumor regression, good compliance and promising survival, especially in TNT (cohort C).
Keywords: Rectal cancer, oxaliplatin, multimodal therapy, total neoadjuvant therapy, survival times (DFS and CSS)
Schlagwörter: Rektumkarzinom, Oxaliplatin, Multimodaltherapie, totale neoadjuvante Therapie, Überlebenszeiten (DFS und CSS)
Persistent Address:
http://dx.doi.org/10.53846/goediss-8414
