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Review of Neoadjuvant Chemotherapy Alone in Locally Advanced Rectal Cancer

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Abstract

Background

Currently, the standard management of locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy followed by resection. Despite the significant improvement in local recurrence, survival benefits are not gained due to distant failure and radiotherapy-associated toxicity. Compliance to adjuvant chemotherapy after preoperative chemoradiotherapy is also poor. Neoadjuvant chemotherapy alone followed by surgery may be an alternative. The objective of this review is to determine the efficacy of neoadjuvant chemotherapy alone in operable LARC.

Materials and Methods

Electronic databases searched (from database inception–December 2013) were Medline, PubMed, Embase, Scopus, Cochrane library, and the Clinical Trials Register. Specific journals were also hand searched. The selection criteria were studies published in English investigating stage II–III non-metastatic rectal cancer patients treated with neoadjuvant chemotherapy (oral, intravenous or rectal route) followed by curative resection. The primary outcome measure was tumour response. Secondary outcome measures included acute toxicity, operative morbidity, R0 resection, local recurrence, overall survival (OS) and disease-free survival (DFS).

Results

One randomised phase III trial, six single-arm phase II trials and one retrospective case series study were eligible for inclusion. Six studies administered fluoropyrimidine-based multiple agent regimens and two studies administered fluorouracil-based monotherapy. The studies with multiple agents and stronger chemotherapy regimens (intravenous and/or oral) followed by delayed surgery showed better tumour response rates. The overall objective response rate was good and ranged from 62.5 to 93.7 %. Pathological complete response ranged from 3.8 to 33.3 %. The R0 resection and compliance rates were also high ranging from 90 to 100 % and 72 to 100 %, respectively. Grade 3–4 toxicities ranged from 2.3 to 39 %. Four- to 5-year OS and DFS ranged from 67.2 to 91 % and 60.5 to 84 %, respectively.

Conclusion

This review demonstrates that neoadjuvant chemotherapy could be affectively administered in LARC and could provide a good alternative to chemoradiotherapy in moderate-risk rectal cancers without compromising short- and long-term outcomes.

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Abbreviations

APR:

Abdominoperineal resection

CAPOX:

Oxaliplatin and capecitabine

CIV:

Continuous intravenous infusion

cPR:

Complete pathological response

CRC:

Colorectal cancer

CRM:

Circumferential resection margin

CRT:

Chemoradiotherapy

DFS:

Disease-free survival

5-FU:

5-Fluorouracil

FLOFOX:

Oxaliplatin, fluorouracil (5-FU) and folinic acid

IFL:

Irinotecan, 5-fluorouracil and leucovorin

ITT:

Intention to treat

IV:

Intravenous

LAR:

Low anterior resection

MRI:

Magnetic resonance imaging

OS:

Overall survival

PRISMA:

Preferred reporting items for systematic reviews and meta-analyses

RCT:

Randomised controlled trial

RECISTs:

Response evaluation criteria in solid tumours

TPE:

Total pelvic exenteration

XELOX:

Oxaliplatin and capacitabine

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Conflict of Interest

All the authors declare no conflict of interests.

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Correspondence to Omer Jalil.

Appendices

Appendix 1 Search Terms with MeSH Headings: Medline

  1. 1.

    Rectal neoplasm (used for tumour rectal, neoplasm rectal, neoplasms rectal, rectal tumours, rectal neoplasms, cancers rectal, cancer rectum, rectum neoplasms, rectal neoplasm, rectal cancer, neoplasm rectum, rectum neoplasm, cancer of rectum, cancer rectal, cancer of the rectum, tumours rectal, neoplasms rectum, rectum cancer, rectal cancers, cancers rectum, rectum cancers and rectal tumour)

  2. 2.

    Preoperative period (used for period preoperative) or preoperative care (used for preoperative procedure, procedures preoperative, procedure preoperative, preoperative procedure, preoperative care, care preoperative)

  3. 3.

    Neoadjuvant therapy (therapies neoadjuvant, treatments neoadjuvant, neoadjuvant treatments, therapy neoadjuvant, neoadjuvant treatment, neoadjuvant therapy, treatment neoadjuvant and neoadjuvant therapies) or combined modality therapy (treatment multimodal, therapy combined modality, treatments multimodal, multimodal treatment, combined modality therapy, combined modality therapies, modality therapy combined, multimodal treatments, modality therapies combined, therapies combined modality)

  4. 4.

    Drug therapy (used for chemotherapies, therapy drug, chemotherapy, drug therapy, therapies drug pharmacotherapy, drug therapies, pharmacotherapies)

Appendix 2 Quality Assessment Tool for Quantitative Studies

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Appendix 3

Table 3 Data extraction form adapted from Higgins and Green [26]. Available from www.cochrane-handbook.org

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Jalil, O., Claydon, L. & Arulampalam, T. Review of Neoadjuvant Chemotherapy Alone in Locally Advanced Rectal Cancer. J Gastrointest Canc 46, 219–236 (2015). https://doi.org/10.1007/s12029-015-9739-7

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  • DOI: https://doi.org/10.1007/s12029-015-9739-7

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