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Optimize the dose of oxaliplatin for locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by radical surgery and adjuvant chemotherapy.

ABSTRACT:

Background

Addition of oxaliplatin to capecitabine remains controversial for locally advanced rectal cancer (LARC). And cumulative oxaliplatin dose (COD) varied among clinical trials showing different therapeutic effects of this regimen. The objective of this study was to explore how COD affected tumor metastasis and patient survival.

Methods

Totally 388 patients diagnosed with stage cII-III rectal cancer and treated with neoadjuvant chemoradiotherapy followed by radical surgery plus adjuvant chemotherapy were consecutively enrolled into this study and retrospectively reviewed. After grouping by total chemotherapy cycle (TCC), influences of COD on adverse effects and patients' survivals were analyzed in each group. Univariate and multivariate survival analyses were performed through Kaplan-Meier approach and COX proportional hazards model, respectively. Age, gender, anemia, differentiation, carcinoembryonic antigen, carbohydrate antigen 19-9, pretreatment clinical stage and postsurgical pathologic stage were used as covariates.

Results

COD 2 emerged as an independent predictor of poorer overall, metastasis-free and disease-free survivals, in patients treated with TCC???7. The hazard ratios were 1.972, 1.763 and 1.637 (P values were 0.021, 0.028 and 0.041), respectively. But it was note-worthy that COD ?460?mg/m² increased incidence of acute toxicities from 38.4 to 70.8% (P?ConclusionsFor LARC patients treated with insufficient TCC (? 7), oxaliplatin of ?460?mg/m² might be needed to improve survival, though it might resulted in more acute toxicities.

SUBMITTER: Chang H

PROVIDER: S-EPMC7268650 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Optimize the dose of oxaliplatin for locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by radical surgery and adjuvant chemotherapy.

Chang Hui H Tao Ya-Lan YL Jiang Wu W Chen Chen C Liu Shi-Liang SL Ye Wei-Jun WJ Gao Yuan-Hong YH

BMC cancer 20200601 1

<h4>Background</h4>Addition of oxaliplatin to capecitabine remains controversial for locally advanced rectal cancer (LARC). And cumulative oxaliplatin dose (COD) varied among clinical trials showing different therapeutic effects of this regimen. The objective of this study was to explore how COD affected tumor metastasis and patient survival.<h4>Methods</h4>Totally 388 patients diagnosed with stage cII-III rectal cancer and treated with neoadjuvant chemoradiotherapy followed by radical surgery p ...[more]

PMID: 32487091

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Project description:Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer.Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life.Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer.ClinicalTrials.gov NCT01558921.

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Dataset Information

Optimize the dose of oxaliplatin for locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by radical surgery and adjuvant chemotherapy.

Background

Methods

Results

Publications

Optimize the dose of oxaliplatin for locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by radical surgery and adjuvant chemotherapy.

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