Systematic Review: Adjuvant Chemotherapy for Locally Advanced Rectal Cancer with respect to Stage of Disease

Background. Recent meta-analysis of 21 randomised controlled trials (RCTs) supports the use of adjuvant chemotherapy for nonmetastatic rectal carcinoma. In order to define a subgroup of patients who can potentially benefit from postoperative adjuvant chemotherapy, this study aims to review trials investigating adjuvant chemotherapy with respect to stage of disease in patients with locally advanced rectal cancer who had undergone surgery for cure (stage II and stage III). Methods. We searched electronic information sources to identify randomised trials evaluating adjuvant chemotherapy in patients with stages II and III rectal cancer with overall survival or disease-free survival as outcomes. Scottish Intercollegiate Guidelines Network notes on methodology were used to assess the methodological quality of the selected studies. Random-effects models were applied to calculate pooled outcome data. Results. Eight studies reporting total of 5527 patients were selected for analysis. Adjuvant chemotherapy was associated with statistically significant improvement in disease-free survival and overall survival compared to surgery alone in both stage II and stage III cancer. Conclusions. This study indicates that both stage II and stage III rectal cancer patients may benefit from postoperative adjuvant chemotherapy. However, the benefits of adjuvant chemotherapy for patients who already had neoadjuvant chemoradiation still remain unknown.

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Preoperative chemoradiotherapy and postoperative chemotherapy with 5-fluorouracil and oxaliplatin versus 5-fluorouracil alone in locally advanced rectal cancer: First results of the German CAO/ARO/AIO-04 randomized phase III trial.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.18_suppl.lba3505 ◽

2011 ◽

Vol 29 (18_suppl) ◽

pp. LBA3505-LBA3505 ◽

Cited By ~ 17

Author(s):

C. Roedel ◽

H. Becker ◽

R. Fietkau ◽

U. Graeven ◽

W. Hohenberger ◽

...

Keyword(s):

Rectal Cancer ◽

Adjuvant Chemotherapy ◽

Primary Endpoint ◽

Locally Advanced ◽

Disease Free Survival ◽

Advanced Rectal Cancer ◽

Preoperative Chemoradiotherapy ◽

Locally Advanced Rectal Cancer ◽

Free Survival ◽

Disease Free

LBA3505 Background: The German CAO/ARO/AIO-94 trial established preoperative chemoradiotherapy (CRT), surgery, and postoperative chemotherapy with 5-FU as standard treatment for locally advanced rectal cancer. With this approach local relapse rates are below 10%. The development of distant metastasis is the predominant mode of failure. Integrating more effective systemic treatment into combined modality therapy was the goal of CAO/ARO/AIO-04. Methods: Between 7/2006-2/2010, patients with rectal cancer within 12 cm from the anal verge and clinical evidence of perirectal fat or lymph node involvement were randomly assigned to receive preoperative CRT, surgery, and adjuvant chemotherapy with 5-FU according to CAO/ARO/AIO-94 (arm 1), or preoperative CRT (50.4 Gy in 28 fractions) with 5-FU (250 mg/m2/days 1-14 and 22-35) and oxaliplatin (50 mg/m2/days 1, 8, 22, 29), surgery, and 8 cycles of adjuvant chemotherapy according to modified FOLFOX6 regimen (arm 2). Disease-free survival was the primary endpoint. We present early secondary endpoints, including acute toxicity, treatment compliance, and pCR-rates. Results: 637 patients were randomly assigned to arm 1 and 628 to arm 2. Full dose preoperative RT and full dose concurrent chemotherapy was delivered in 97% and 74% of patients in both arms, respectively. Preoperative grade 3/4 toxicity occurred in 21.6% in arm 1 and in 22.9% in arm 2. The R0-resection rate was 95.4% in both arms, and abdominoperineal resections were limited to 11.9% and 12.2% in arms 1 and 2, respectively. Overall postoperative complications were not different between both arms (21.0% and 21.9%). The pCR rate (ypT0N0) was 13.1% in arm 1 and 17.6% in arm 2 (p = 0.033, Cochran-Mantel-Haenszel Chi-Squared Test without continuity correction for conditional independence of pCR rate in the two treatment arms in each stratum). Conclusions: Inclusion of oxaliplatin to 5-FU based CRT was well tolerated and associated with increased pCR-rates compared with 5-FU-CRT alone. Longer follow-up is necessary to evaluate the primary endpoint, disease-free survival.

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Preoperative Chemoradiotherapy and Postoperative Chemotherapy with Capecitabine +/- Oxaliplatin in Locally Advanced Rectal Cancer: Interim Analysis for Disease-Free Survival of Petacc 6

Annals of Oncology ◽

10.1093/annonc/mdu333.8 ◽

2014 ◽

Vol 25 ◽

pp. iv170 ◽

Cited By ~ 1

Author(s):

H.J. Schmoll ◽

K. Haustermans ◽

T.J. Price ◽

B. Nordlinger ◽

R. Hofheinz ◽

...

Keyword(s):

Rectal Cancer ◽

Interim Analysis ◽

Locally Advanced ◽

Disease Free Survival ◽

Advanced Rectal Cancer ◽

Preoperative Chemoradiotherapy ◽

Locally Advanced Rectal Cancer ◽

Postoperative Chemotherapy ◽

Free Survival ◽

Disease Free

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Intensification of neoadjuvant therapy in patients with locally advanced rectal cancer

Pelvic Surgery and Oncology ◽

10.17650/2686-9594-2021-11-2-19-28 ◽

2021 ◽

Vol 11 (2) ◽

pp. 19-28

Author(s):

Z. Z. Mamedli ◽

A. V. Polynovskiy ◽

D. V. Kuzmichev ◽

S. I. Tkachev ◽

A. A. Aniskin

Keyword(s):

Rectal Cancer ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Disease Free Survival ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Control Group ◽

Free Survival ◽

Disease Free

The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.

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