结肠癌全身辅助化疗的进展

Ⅲ期结肠癌的术后辅助化疗具有明显的生存效益,主要采用以5-FU为基础的全身化疗方案,包括5-FU/Lev、Mayo(FU/LV)方案、持续小剂量灌注(PVI)5-FU、口服氟尿嘧啶类抗癌药(UFT、Xeloda)等;5-FU合用草酸铂可以进一步提高疗效,与依立替康合用的疗效有待于进一步研究。Ⅱ期结肠癌术后辅助化疗的生存效益目前尚有争议,对高危Ⅱ期肠癌患者也应考虑行术后辅助化疗。本文综述了近年来结肠癌术后辅助化疗的进展。     

Overview of preoperative and postoperative therapy for colorectal cancer: the European and United States perspectives

Surgery is the primary modality for cure in patients with localized colorectal cancer. However, despite potential curative surgery, the risk of recurrence is high. In colon cancer, the role of adjuvant chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV) is now established in stage III disease. The benefit of adjuvant treatment in stage II disease is likely to be small, and studies performed thus far have been generally underpowered to detect what might be a clinically significant effect on survival. Whereas bolus scheduling of 5-FU and LV is favored in North America, infusion of 5-FU/LV is preferred in Europe. Indeed, infused 5-FU/LV may be a safer partner with new drugs such as oxaliplatin and irinotecan. Oral fluoropyrimidines are attractive agents that might one day replace parenteral 5-FU. In rectal cancer, postoperative combined chemoradiation was recommended as standard practice in stages II and III disease. Despite a lack of randomized data demonstrating clinical benefit, preoperative chemoradiation has been increasingly used in patients with T3 disease in North America. However, preoperative radiation therapy is more frequently used in Europe. There are discrepancies in pathologic reporting of circumferential resection margin involvement and lymph node status between the United States and Europe. Standardized reporting with improved preoperative imaging would allow patients with truly early-stage disease to undergo more conservative management and be spared the morbidity and mortality of unnecessary adjuvant or neoadjuvant treatment.     

Adjuvant radio-chemotherapy in stage II-III rectal cancer with 24-hour infusion of high-dose 5-fluorouracil and folinic acid: evaluation of feasibility.

BACKGROUND: Postoperative radio-chemotherapy has been established as standard treatment for stage II and III rectal cancer patients in the last decade. To improve the efficacy of this therapy, we decided to evaluate continuous 24-hour infusion of 5-fluorouracil (5-FU) with folinic acid (FA) in combination with local radiation versus standard bolus 5-FU/FA with local radiation in a randomized study. Here we report on the first 28 patients to receive the experimental treatment. PATIENTS AND METHODS: Patients with stage II and III rectal cancer received weekly 2-hour infusions of FA 500 mg/m2 followed by continuous 24-hour infusions of 5-FU 2,600 mg/m2 postoperatively via a Port-A-Cath system. The first cycle included 8 consecutive weekly administrations, the 1st-4th in full dose, the 5th-8th with 50% reduced dose while local irradiation (45 or 50.4 Gy) was performed. Thereafter, two further chemotherapy cycles (6 weekly administrations, 100% dose) followed. RESULTS: 28 patients received continuous 5-FU/FA treatment, of whom only 21 were evaluable for tolerability. 19 patients (90.4%) completed the first cycle, only 14 patients entered the second treatment cycle. Especially during the combined radiochemotherapy, increased toxicity was observed with grade III/IV diarrhea (n = 2), nausea (n = 1), leukopenia (n = 1), and cardiac toxicity (n = 1). CONCLUSION: The high rate of premature treatment dropout indicate that the chosen schedule of weekly high-dose 5-FU/FA continuous infusion and combined postoperative radiotherapy should not be recommended for further use in postoperative adjuvant treatment.     

Have the changes in treatment of rectal cancer made a significant difference to our patients?

The treatment for patients with locally advanced, resectable rectal cancer has evolved over the years. Various combinations and sequences of chemotherapy, radiation therapy, and total mesorectal excision (TME)-based surgery are the mainstay of current therapy. Preoperative combined chemoradiation, followed by surgery, is now the preferred treatment strategy, with the majority of patients receiving either infusion fluorouracil (5-FU) or capecitabine (Xeloda) with radiation. Clinical trials with oxaliplatin (Eloxatin)-based neoadjuvant chemoradiation have not shown improvement in the pathologic complete response rate (pCR) compared with 5-FU; however, final data addressing local recurrence rates and disease-free survival are pending.The use of adjuvant chemotherapy following preoperative chemoradiation and surgery has not been optimally defined. Some studies have shown that patients who obtained significant pathologic downstaging after chemoradiation and surgery have improved survival with the use of adjuvant chemotherapy. Since FOLFOX (folinic acid, 5-FU, and oxaliplatin) is the preferred adjuvant chemotherapy regimen for stage III colon cancer based on randomized clinical trial results, FOLFOX is also recommended for rectal cancer patients as an adjuvant therapy approach.     

Current Options for the Management of Rectal Cancer

Opinion statement Patients diagnosed with rectal cancer should undergo locoregional staging with transrectal endoscopic ultrasound (EUS) or surface coil array MRI of the pelvis if that technique is available. Patients thought to have more than very early stage (T1 or T2) disease should undergo abdominal imaging as well by CT or MRI, and chest imaging with either CXR or preferably CT. The care of rectal cancer patients should be coordinated amongst an experienced multidisciplinary team to maximize the chance of cure and to minimize both local recurrence and complications of therapy. For patients with very early stage disease (T1N0 or T2N0), local resection with or without chemoradiation may be adequate therapy, but these patients must be selected carefully and should be without any poor prognostic factors. For the majority of patients with T3N0 or greater rectal cancer, standard therapy consists of neoadjuvant continuous 5-FU and radiation followed by surgery and further chemotherapy (either with 5-FU, capecitabine, or FOLFOX). The use of capecitabine, irinotecan, and oxaliplatin during radiotherapy shows promise, but remains investigational pending results of phase III studies. Neoadjuvant therapy is preferred because it decreases local recurrence and appears to result in improved postoperative bowel function in comparison with postoperative therapy. Select patients with high (>10 cm from the anal verge) uT3N0 tumors may be at sufficiently low risk of local recurrence to justify omission of radiotherapy. Patients who experience pathologic complete response to radiotherapy should still receive postoperative adjuvant chemotherapy to reduce systemic recurrence risk until data demonstrate that this is not necessary. Patients with stage IV rectal cancer may still require local therapy with radiation, surgery, or both; however, care should be taken in these patients that chemotherapy is not excessively delayed as this is the one modality in this case that can result in improved survival.     

The present situation regarding postoperative adjuvant chemotherapy

The purpose of postoperative adjuvant chemotherapy is to achieve a higher or rate of surgical radical cure and to eliminate recurrence of cancer. There are many differences between colon cancer and rectal cancer. Recurrence of colon cancer almost always metastasizes to liver and lung Adjuvant chemotherapy is indicated for stage III and high risk stage II. Standard adjuvant chemotherapy is a combination of Leucovorin and 5-FU, or a combination of oxaliplatin, 5-FU and Leucovorin. Combination treatment with VEGF antibody and EGFR antibody has shown no evidence of effectiveness in adjuvant chemotherapy. In rectal cancer, radiation is the standard form of neoadjuvant therapy. In the future, treatment of colorectal cancer may make remarkable improvement with the introduction of new drugs.     

Adjuvant and neoadjuvant chemoradiation therapy for primary colorectal cancer

The management of rectal cancer presents substantial challenges. Patients with T3 and/or node-positive rectal cancers are at high risk for local failure and distant metastases (DM). Adjuvant radiation has been shown to decrease local recurrence (LR) rates; however, this local therapy has not been demonstrated to improve survival when compared to surgery alone. In several prospective randomized trials adjuvant chemoradiation with 5-fluorouracil-(5-FU)-based chemotherapy improved LR rates, DM rates, and overall survival (OS). The optimal chemotherapeutic regimen has not been determined; however, studies comparing standard IV bolus 5-FU administration with continuous infusion (CI) 5-FU demonstrated that CI administration was superior. Preoperative therapy has potential advantages over adjuvant therapy such as less acute bowel toxicity and improved sphincter preservation. Preoperative chemoradiation has been shown in several studies to improve LR rates and OS when compared to surgery alone. Our current approach to patients with resectable T3 or N1 cancer in the distal two-thirds of the rectum on preoperative staging is preoperative chemoradiation with planned postoperative chemotherapy. This regimen offers the best chance for local control and disease-free survival while potentially downstaging the tumor and improving sphincter preservation.     

Preoperative or Postoperative Therapy for Stage II or III Rectal Cancer: An Updated Practice Guideline

AimsUncertainty remains regarding the optimal therapy for patients with stage II or III rectal cancer. Systematic reviews and practice guidelines on preoperative and postoperative therapy for rectal cancer were published by the Gastrointestinal Cancer Disease Site Group in 2003 and 2000, respectively. The systematic reviews were updated and revised and new recommendations for preoperative and postoperative therapy were developed based on the updated body of evidence. The following research questions were addressed: After appropriate preoperative staging tests, should patients with resectable clinical stage II or III rectal cancer be offered preoperative radiotherapy (with or without chemotherapy)? What is the role of postoperative radiotherapy and/or chemotherapy for patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy, in terms of improving survival and delaying local recurrence?Materials and methodsThe MEDLINE, EMBASE and Cochrane Library databases, as well as meeting proceedings from the American Society of Clinical Oncology, were searched for reports of randomised controlled trials and meta-analyses comparing preoperative or postoperative therapy with surgery alone or other preoperative or postoperative therapy for stage II or III rectal cancer. The draft practice guideline and systematic reviews were distributed through a mailed survey to 129 health care providers in Ontario for review.ResultsSystematic reviews on preoperative and postoperative therapy for rectal cancer were developed. On the basis of the evidence contained in these reviews, the Gastrointestinal Cancer Disease Site Group drafted recommendations. Of the 33 practitioners who responded to the mailed survey, 97% agreed with the draft recommendations as stated, 88% agreed that the report should be approved as a practice guideline and 94% indicated that they were likely to use the guideline in their own practice.ConclusionsPreoperative chemoradiotherapy is preferred, compared with standard fractionation preoperative radiotherapy alone, to decrease local recurrence. Preoperative chemoradiotherapy is also preferred, compared with a postoperative approach, to decrease local recurrence and adverse effects. For patients with relative contraindications to chemotherapy in the preoperative period, an acceptable alternative is preoperative radiotherapy alone followed by surgery. Patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy should be offered postoperative therapy with concurrent chemoradiotherapy plus fluoropyrimidine-based chemotherapy.     

Adjuvant and neoadjuvant radiotherapy and concurrent radiochemotherapy for rectal cancer

Radical surgery with negative margins remains the most important prognostic factor in the treatment of rectal cancer. Combined modality treatment is the recommended standard adjuvant therapy for patients with locally advanced rectal cancer in the USA and in Germany. During the last decade substantial progress has been made in treatment modalities: surgical management currently includes a broad spectrum of operative procedures ranging from radical operations to innovative sphincter-preserving techniques. Specialized groups have reported excellent local control rates with total mesorectal excision (TME) alone. New and improved radiation techniques (conformai radiotherapy, intraoperative radiotherapy) and innovative schedules (protracted intravenous infusion, chronomodulated infusion) and combinations (oxaliplatin, irinotecan) of chemotherapy may have the potential to further increase the therapeutic benefit of adjuvant treatment. Moreover, the basic issue of timing of radio-(chemo-) therapy preoperative versus postoperative within a multimodality regimen is currently being addressed in prospective trials. Evidently, the current monolithic approaches, established by studies conducted more than a decade ago, to apply either the same schedule of postoperative radiochemotherapy to all patients with stage II/III rectal cancer or to give preoperative intensive short-course radiation according to the Swedish concept for all patients with resectable rectal cancer irrespective of tumor stage and treatment goal (e.g. sphincter preservation), need to be questioned. This review will discuss different irradiation settings in more recent and ongoing studies of perioperative radiotherapy for rectal cancer and will focus on the issue which patient should receive radiotherapy at all, and if so, how and when?     

Efficacy of postoperative adjuvant chemotherapy for colorectal cancer

We attempted postoperative adjuvant chemotherapy for stage II or III colorectal cancer. To investigate the efficacy of the adjuvant chemotherapy, we retrospectively reviewed all 293 colorectal cancer patients who underwent curative resection between 1990 and 1996 in Kurume University Hospital. The patients were divided into two groups according to whether or not they received postoperative adjuvant chemotherapy. Patients in Group 1 (n = 156) underwent resection followed by administration of oral fluorouracil. Some also received intravenous 5-FU or MMC after surgery. Patients in Group 2 (n = 95) underwent surgery alone. The disease-free survival rate in Group 1 was significantly higher than that in Group 2, but only for those with rectal cancer, with no significant difference for those with colon cancer. The results were also analyzed according to tumor stage, degree of lymphatic and venous invasion, and histological grading. Findings were similar between the two groups for those with stage II, stage IIIa, a low grade of lymphatic and venous invasion, and well-differentiated adenocarcinoma. Postoperative adjuvant chemotherapy in colorectal cancer might reduce the risk of recurrence, particularly in cases of rectal cancer. However, postoperative adjuvant chemotherapy was insufficient for those with highly advanced cancer or a biologically aggressive tumor.     

Neoadjuvant chemoradiation for rectal cancer: is more better?

Neoadjuvant chemoradiation is now considered the clear preferable adjuvant standard of care in the management of stage II/III rectal cancer. Neoadjuvant fluorouracil (5-FU) plus radiation results in a decrease in local relapse rates and a favorable toxicity profile in comparison with postoperative adjuvant 5-FU plus radiation therapy. Recent nonrandomized comparative studies have shown that capecitabine (Xeloda) plus radiation result in downstaging and pathologic complete responses equivalent to those of 5-FU plus radiation, making this combination an acceptable alternative neoadjuvant treatment. The addition of oxaliplatin (Eloxatin) or irinotecan (Camptosar) to 5-FU or capecitabine concurrently with radiation therapy appears to result in more favorable pathologic responses in phase I/II trials. These combinations should be investigated further in larger phase III studies before they are endorsed in the routine neoadjuvant treatment of rectal cancer. This article will review the progress of chemoradiation over the past 2 decades, current standards of care, and investigational treatments in the neoadjuvant treatment of rectal cancer.     

Role of Combined-Modality Therapy in the Management of Locally Advanced Rectal Cancer

The majority of patients with nonmetastatic rectal cancer are candidates for an aggressive multimodality approach with curative intent. Preoperative staging is critical in determining which patients should be offered neoadjuvant therapy. Available staging tools include digital rectal examination, transrectal ultrasound, computed tomography, positron-emission tomography, and magnetic resonance imaging scans. Magnetic resonance imaging has emerged as the most accurate staging modality in experienced centers. Multidisciplinary preoperative patient evaluation, better staging techniques, neoadjuvant chemoradiation, acceptance of shorter distal rectal margins, and transanal excision of T1 N0 rectal tumors in close proximity to the anal sphincter have resulted in decreased rates of abdominoperineal resections. Total mesorectal excision has been adopted as the standard surgical approach because of a reduction in rates of pelvic relapse. Preoperative and postoperative radiation therapy was shown to decrease the local recurrence rate, but not overall survival, in patients with resectable rectal cancer. The addition of chemotherapy to radiation was consistently shown to improve local control, and in some trials, improved overall survival. Neoadjuvant combined chemotherapy and radiation therapy are superior to adjuvant combined-modality therapy because of higher rates of sphincter preservation, less toxicity, and lower local recurrence rates. For patients with stage II or III disease, neoadjuvant continuous-infusion 5-fluorouracil (5-FU), concurrently with pelvic radiation, followed by postoperative 5-FU–based chemotherapy, remains the standard multimodality approach. Ongoing trials are testing the integration of newer cytotoxic agents such as capecitabine, oxaliplatin, irinotecan, and biologic agents such as cetuximab and bevacizumab to chemoradiation.     

The use of capecitabine in the combined-modality therapy for rectal cancer

Locally advanced rectal adenocarcinoma is treated by combined-modality therapy, which consists of surgery, chemotherapy, and radiation therapy. A series of randomized trials established a preferred treatment sequence of preoperative radiation therapy and 5-fluorouracil(5-FU)-based chemotherapy, total mesorectal excision, and adjuvant 5-FU-based chemotherapy for patients with stage II/III disease. Capecitabine is an oral prodrug of 5-FU that has potential advantages compared with intravenous 5-FU, including ease of administration and potentially increased therapeutic effect. Capecitabine is converted by a 3-step enzymatic process; the last step involves the enzyme thymidine phosphorylase, which is overexpressed in tumor tissues and is stimulated by concurrent radiation therapy. Over the past 5 years, several phase I/II trials of capecitabine-based therapy were reported. This review discusses the evolution of combined-modality therapy for rectal cancer with specific attention given to the use of capecitabine in conjunction with radiation therapy.     

Use of adjuvant chemotherapy and radiation therapy for rectal cancer among the elderly: a population-based study.

PURPOSE: Combined adjuvant fluorouracil (5-FU)-based chemotherapy with radiation is now the standard of care for locally advanced rectal cancer in the United States. We investigated the use of these treatments for stages II and III rectal cancer among the elderly and the effectiveness of these treatments on a population-based scale. PATIENTS AND METHODS: The linked Surveillance, Epidemiology, and End-Results-Medicare database was used to identify 1,807 Medicare beneficiaries > or = 65 years of age with stage II or III rectal cancer who underwent surgical resection between 1992 and 1996. We excluded members of a health maintenance organization in the 12 months before or 4 months after their diagnosis and those who died within 4 months of diagnosis. We used multivariate analysis to identify factors associated with combined 5-FU and radiation therapy, and propensity score methodology to determine survival benefit for those treated. RESULTS: We found that 37% of patients received both adjuvant 5-FU and radiation therapy, 11% 5-FU alone, and 14% radiation alone. Decreasing age, increasing lymph node positivity, comorbid conditions, and nonblack race were associated with increased probability of treatment with 5-FU and radiation. Combined chemotherapy/radiation therapy was associated with improved survival for stage III (relative risk, 0.71; 95% confidence interval, 0.56 to 0.90), but not for stage II rectal cancer (relative risk, 0.89; 95% confidence interval, 0.70 to 1.14). CONCLUSION: The association of combined treatment with improved survival in node-positive disease was similar to that observed in other studies. In the absence of data from well-designed randomized controlled trials, our observational data support efforts on the part of clinicians to make appropriate referrals and provide combined treatment for elderly patients with stage III rectal cancer.     

Therapy for early-stage colorectal cancer

Surgery is the only curative option for patients with colorectal cancer. The goal of other modalities, such as chemotherapy, immunotherapy, and radiotherapy, is to prolong survival and reduce the risk of recurrence. Adjuvant treatment is mandatory for patients with stage III colon cancer. At present, 6 months of fluorouracil (5-FU) plus leucovorin (folinic acid) can be considered standard therapy. The data on stage II colon cancer are less convincing, and perhaps only subgroups benefit from adjuvant therapy. Patients with stage II disease should be encouraged to participate in randomized trials. Outside of such trials, one can consider prognostic factors in the decision to offer adjuvant therapy. Patients with T3 or N1-3 M0 rectal cancer should receive combined-modality therapy, i.e., 5-FU-based chemotherapy and irradiation. Until ongoing trials answer the question of whether a patient should be irradiated preoperatively or postoperatively, the type of surgery determines the timing of irradiation. If the tumor is amenable to a sphincter-preserving operation, surgery can be followed by radiation therapy. In patients with fixed tumors and those in whom resectability is an issue, prolonged preoperative radiotherapy is more appropriate. Ongoing trials should optimize existing adjuvant therapy (by achieving an ideal balance between toxicity and effectiveness) and integrate the advantages of recently approved drugs.     

Outcomes of Preoperative Chemoradiotherapy and Combined Chemotherapy with Radiotherapy Without Surgery for Locally Advanced Rectal Cancer

Purpose: To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery. Materials and Methods: A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation. Results: There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (p<0.01). The respective 5 yearoverall survival rates were 70.3% and 0% (p<0.01). The 5 yearoverall survival rates in Gr.I for patients who received surgery within 56 days after complete CCRT as compared to more than 56 days were 69.5% and 65.1% (p0.91). Preoperative CCRT used for 12 of 30 patients in Gr.I (40%) with lower rectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. Conclusions: The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.     

Progress in adjuvant therapy for colorectal cancer

The progress and role of adjuvant therapy for resectable colorectal cancers are reviewed herein. 5-FU/leucovorin is considered the standard treatment in the postoperative adjuvant chemotherapy for Dukes'C colon cancer. The oral 5-FU prodrugs, such as UFT and capecitabine, will replace 5-FU infusion in the adjuvant chemotherapy in the near future. In Dukes'B colon cancer, the results of postoperative adjuvant chemotherapy are controversial. Many randomized trials in the USA and Europe have demonstrated that pre- or postoperative radiation therapy for rectal cancer decreases local recurrences but has no additional benefit on survival compared with 5-FU-based adjuvant chemotherapy. Adjuvant radiation therapy for rectal cancer is not widely used in Japan, while chemotherapy is considered the adjuvant treatment of choice. The local recurrences of rectal cancer is a surgeon-related phenomenon: the surgical technique used and the skill of the surgeon are major factors influencing outcome.     

Perioperative radiotherapy and concurrent radiochemotherapy in rectal cancer

Combined modality treatment is the recommended standard adjuvant therapy for patients with locally advanced rectal cancer in the United States and Germany. During the last decade substantial progress has been made in treatment modalities, and surgical management currently includes a broad spectrum of operative procedures ranging from radical operations to innovative sphincter-preserving techniques. Specialized groups have reported excellent local control rates with total mesorectal excision (TME) alone. New and improved radiation techniques (conformal and intraoperative radiotherapy) and innovative schedules (protracted intravenous and chronomodulated infusion) and combinations (oxaliplatin and irinotecan) of chemotherapy may have the potential to further increase the therapeutic benefit of adjuvant treatment. Moreover, the basic issue of timing (pre- or postoperative) within a multimodal regimen is currently being addressed in prospective trials. Evidently there is a need to question the current monolithic approaches, which were established by studies conducted more than a decade ago. It is also under discussion whether to apply the same schedule of postoperative radiochemotherapy to all patients with stage II/III rectal cancer, or to give preoperative intensive short-course radiation according to the Swedish concept for all patients with resectable rectal cancer irrespective of tumor stage and treatment goal (e.g., sphincter preservation). This review discusses different irradiation settings in more recent and ongoing studies of perioperative radiotherapy for rectal cancer, and focuses on the issue of which patient should receive radiotherapy (if at all), and if so, how and when.     

An overview of adjuvant systemic chemotherapy for colon cancer

This article summarizes the progress of adjuvant systemic chemotherapy of colon cancer. The study by Moertel et al that showed that the combination of 5-fluorouracil (5-FU) and levamisole in the adjuvant setting reduced mortality by 33% in stage III colon cancer; 5-FU/leucovorin (LV) became the standard of care in the adjuvant treatment of colon cancer after it showed superiority to 5-FU/levamisole. However, no standard schedule of 5-FU/LV has been established. The fortnightly regimen of bolus 5-FU/LV and continuous infusion 5-FU (LV5FU2) has the same efficacy as and is less toxic than the monthly regimen of bolus 5-FU/LV. Oxaliplatin combined with 5-FU and LV (FOLFOX4) is the first combination to demonstrate significant superiority in 3-year disease-free survival as compared with 5-FU/LV in the adjuvant treatment of colon cancer. Three-year disease-free survival is an excellent predictor of 5-year overall survival and, in future studies, can serve as a reliable endpoint that is associated with reproducible 5-year overall survival. Results of studies testing irinotecan combined with 5-FU and LV are not yet available. Adjuvant chemotherapy for patients with stage II colon cancer is a controversial subject. Because the available data suggest that stage II patients benefit from adjuvant chemotherapy, although to a lesser extent than patients with stage III disease, all patients with stage III and high-risk stage II disease should be offered adjuvant treatment with the new standard of care, FOLFOX4. Future studies in adjuvant therapy for colon cancer will explore oxaliplatin and 5-FU with or without antiangiogenesis or anti-epidermal growth factor agents.     

Improving chemoradiotherapy in rectal cancer

The optimal management of rectal cancer remains a major challenge for oncologists. The treatment of stage II/III rectal cancer has historically been associated with a high risk of local recurrence and poor survival, which led to the development of adjuvant treatments in the hope of improving outcomes. The approach to adjuvant therapy for rectal cancer currently varies widely between Europe and the U.S. Postoperative adjuvant chemoradiation is the standard of care in the U.S. In contrast, in Europe, because there is a greater emphasis placed on preoperative imaging, meticulous surgical technique, and accurate pathologic reporting of the circumferential or radial margin, preoperative treatment (radiotherapy and chemoradiation) is used widely. The aims of preoperative radiotherapy and chemoradiation are to facilitate a curative resection (R0) and to increase the chance of performing sphincter-sparing procedures, and, therefore, to improve both survival and quality of life. This article reviews the clinical trials that led to these diverging standards of care. An interesting new approach in chemoradiation is the use of the oral fluoropyrimidine capecitabine as a combination partner for radiotherapy. Preclinical studies have demonstrated that the combination of capecitabine and radiotherapy has highly enhanced antitumor activity. This is most likely attributable to the upregulation of thymidine phosphorylase (the rate-limiting enzyme needed to convert capecitabine to 5-fluorouracil [5-FU]) in tumor cells following radiotherapy. A phase I study has consequently been performed to establish a feasible chemoradiotherapy combination. Capecitabine has the potential to replace bolus or continuous infusion 5-FU as the standard treatment for rectal cancer and offers a potentially enhanced therapeutic ratio. Oral chemotherapy has the additional advantage of simplifying chemoradiation and providing a treatment that is more appealing to patients.