Integration of Novel Agents into Combined-Modality Treatment for Rectal Cancer Patients

Rödel, Claus; Sauer, Rolf

doi:10.1007/s00066-007-9000-9

Cited by 83 publications

(58 citation statements)

References 80 publications

(52 reference statements)

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“…Furthermore, inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) has been shown beneficial in metastatic colorectal cancer (180)(181)(182). In clinical trials for rectal cancer, all these compounds have been incorporated as part of CRT regimens (183).…”

Section: New Crt Regimensmentioning

confidence: 99%

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Inhibitory effects of oxaliplatin in experimental radiation treatment of colorectal carcinoma: does oxaliplatin improve 5-fluorouracil-dependent radiosensitivity?

Folkvord

Flatmark

Seierstad

et al. 2008

Radiotherapy and Oncology

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Section: New Crt Regimensmentioning

confidence: 99%

“…• Oxaliplatin: Several phase I and II studies, including the ongoing LARC-RRP study, have been conducted with oxaliplatin combined with 5-FU based CRT in LARC with relatively high pCR rates of 16-28% (183,(195)(196)(197). Randomized phase III trials are still recruiting patients (Table 5) (51,(198)(199)(200).…”

Section: New Crt Regimensmentioning

confidence: 99%

Inhibitory effects of oxaliplatin in experimental radiation treatment of colorectal carcinoma: does oxaliplatin improve 5-fluorouracil-dependent radiosensitivity?

Folkvord

Flatmark

Seierstad

et al. 2008

Radiotherapy and Oncology

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“…The German Rectal Cancer Study Group and other groups [3][4][5][6] have shown that preoperative radiotherapy (RT) combined with 5-FU chemotherapy (used as a radiosensitizer) improves locoregional tumor control with less acute and chronic toxicity compared with postoperative radiochemotherapy (RCT). Therefore, this preoperative setting became the standard treatment for stage II and III rectal cancer, as defined by the Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC) [7].…”

Section: Introductionmentioning

confidence: 99%

“…Although local control rates were improved by this preoperative multimodal strategy, distant metastases still remained the major mode of failure and recurrence rates of 30%-45% have been reported 5 years after treatment [1,3]. Intensified chemotherapy regimens, including standard RCT with 5-FU monotherapy and additional oxaliplatin, have been tested in different clinical trials to increase the rate of complete pathological tumor regression (pCR) and long-term progression-free survival [6]. After chemotherapy treatment modalities are intensified, the risk of high-grade acute toxicity during therapy increases [8 -11].…”

Section: Introductionmentioning

confidence: 99%

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Gender-Specific Acute Organ Toxicity during Intensified Preoperative Radiochemotherapy for Rectal Cancer

et al. 2011

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Learning Objectives After completing this course, the reader will be able to: Describe present strategies of treatment of locally advanced rectal cancer and ongoing clinical trials, including neoadjuvant radiochemotherapy with 50.4 Gy and concomitant 5-FU +/− oxaliplatin.Define the basic clinical parameters, with special emphasis on gender and BMI, correlating with radiochemotherapy-associated side effects in rectal cancer patients and differences in severity of toxicity. CME This article is available for continuing medical education credit at CME.TheOncologist.com Patients with locally advanced rectal cancer (cUICC stages II/III) are typically treated with preoperative 5-fluorouracil–based (5-FU–based) radiochemotherapy (RCT). However, trials are currently being conducted to improve the complete remission rates and the systemic control by combining 5-FU with oxaliplatin. The primary objective was to identify the subgroups of rectal cancer patients who were at risk for high-grade toxicity. All 196 patients who were included in the present study were treated with 50.4 Gy and chemotherapy that included either 5-FU (n = 115) or 5-FU+oxaliplatin (n = 81). The preoperative RCT was followed by a total mesorectal excision and adjuvant chemotherapy. Acute toxicity was monitored weekly and a toxicity grade ≥3 (Common Toxicity Criteria) for a skin reaction, cystitis, proctitis, or enteritis was defined as high-grade acute organ toxicity. After RCT with 5-FU+oxaliplatin, complete tumor remission was achieved in 13.6% of the patients and in 11.3% after RCT with 5-FU alone. Complete irradiation dosages of 50.4 Gy were given to 99% (5-FU) and 95% (5-FU+oxaliplatin) of the patients. Concomitant chemotherapy was fully administered in 95% of the patients treated with 5-FU compared with the 84% of patients treated with 5-FU+oxaliplatin. A significantly higher proportion of acute organ toxicity was found in the patients who were treated with 5-FU+oxaliplatin compared with those who were treated with 5-FU. Additionally, women with a low body mass index were at the highest risk for acute organ toxicity. These results suggest that there are basic clinical parameters, such as gender and body mass index, that may be potential markers for generating individual risk profiles of RCT-induced toxicity.

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Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

Petersen

Harling

Kirkeby

et al. 2012

Cochrane Database of Systematic Reviews

228

170

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Background Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery-which remains the mainstay of treatment for resectable primary tumours-postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes´C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes´C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. Objectives We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). Search methods CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect*-2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour-3. Adjuv*-4. Chemother*-5. Postoper* Selection criteria Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen.

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Integration of Novel Agents into Combined-Modality Treatment for Rectal Cancer Patients

Abstract: Phase III trials are needed to determine, if these novel combination regimens offer an advantage compared with 5-FU-based combined modality. These studies have now been started in Germany (CAO/ARO/AIO-04), Europe (PETACC 6), and the USA (NSAPB-R04, E5204 Intergroup Trial).

Cited by 83 publications

References 80 publications

Inhibitory effects of oxaliplatin in experimental radiation treatment of colorectal carcinoma: does oxaliplatin improve 5-fluorouracil-dependent radiosensitivity?

Inhibitory effects of oxaliplatin in experimental radiation treatment of colorectal carcinoma: does oxaliplatin improve 5-fluorouracil-dependent radiosensitivity?

Gender-Specific Acute Organ Toxicity during Intensified Preoperative Radiochemotherapy for Rectal Cancer

Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

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