Adjuvant chemotherapy for colorectal cancer

Colorectal cancer is the second leading cause of cancer death in Western countries. If surgery remains the only cure, recurrence rates for colon cancer range from 30% to 60% for stage III tumors. Adjuvant chemotherapy is the standard treatment for stage III colon tumors and consists of monthly administration of bolus 5-fluorouracil and leucovorin for 5 consecutive days a month over a 6-month period (Mayo regimen). Adjuvant chemotherapy for stage II colon cancer remains controversial, and its administration is not routinely recommended except in certain high-risk and selected patients. Immunotherapy, new drug-based therapies or combinations, and cyclooxygenase-2 inhibitors are being tested in the adjuvant setting. Total mesorectum excision is now the gold standard surgical technique for rectal cancer resection, and this procedure has dramatically decreased local recurrence. Nevertheless, adjuvant chemoradiotherapy is commonly indicated in the United States. In Europe, neoadjuvant radiotherapy is recommended for stage II and III resectable rectal cancers; the role of chemotherapy remains mostly investigational.     

Adjuvante Therapie des Kolon- und Rektumkarzinoms

Specific postoperative adjuvant chemotherapy significantly improves overall survival of patients with stage III colon cancer and lowers the rates of local disease recurrence of stage II and III rectal cancer after curative surgical treatment. Because of the high incidence of local and distant disease recurrence, great efforts are now being made in clinical studies to transfer the benefits of 5-fluoropyrimidine-based combination chemotherapy known from palliative stages, to the adjuvant situation. In the adjuvant treatment of curative resected stage III colon cancer, the addition of oxaliplatin has now been established, which can also be used in exceptional cases in stage II. Standard in the treatment of stage II and stage III rectal cancer is the pre-operative neo-adjuvant combined radiotherapy and chemotherapy based on 5-fluorouracil followed by post-operative chemotherapy or alternatively, preoperative irradiation with 25 Gy delivered in 5 fractions in 1 week followed by adjuvant chemotherapy.     

Efficacy of Surgery and Adjuvant Therapy in Older Patients With Colorectal Cancer: A STROBE-compliant article

The present study aimed to assess the efficacy of surgery and adjuvant therapy in older patients (age ≥70 years) with colorectal cancer (CRC). Older CRC patients are under-represented in available clinical trials, and therefore their outcomes after receiving surgery and adjuvant therapy are unclear. From two prospective Swedish databases, we assessed a cohort of 1021 patients who underwent curative surgery for stage I, II, or III primary CRC, with or without adjuvant chemotherapy/radiotherapy. Of the patients with colon cancer (n = 467), 182 (39%) were aged <70 years, 162 (35%) aged 70 to 80 years, and 123 (26%) were aged ≥80 years. Of rectal cancer patients (n = 554), 264 (48%) were aged <70 years, 234 (42%) aged 70 to 80 years, and 56 (10%) aged ≥80 years. Older patients with either colon or rectal cancer had higher comorbidity than did younger patients. Older patients with colon cancer had equivalent postoperative morbidity and 30-day mortality to younger patients. Rectal cancer patients aged ≥80 years had a higher 30-day mortality than younger patients (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.6–4.55; P = 0.03). For either colon or rectal cancer, adjuvant chemotherapy compromised the 5-year overall survival (OS) of older patients with stage II disease and had no effect on those with stage III disease. Receiving adjuvant chemotherapy was a poor factor of OS for older patients with either colon (HR 1.88, 95% CI: 1.20–4.35, P = 0.03) or rectal cancer (HR 1.72, 95% CI: 1.05–2.26, P = 0.004). Preoperative short-course radiotherapy improved both OS and local control for older patients with stage III rectal cancer and had no effect on those with stage II disease. Radiotherapy was a favorable factor for the OS of the older patients with rectal cancer (HR 0.42, 95% CI: 0.21–3.57, P = 0.01). In conclusion, Older CRC patients had equal safety of surgery as younger patients, except rectal cancer patients aged ≥80 years that had a higher mortality. Adjuvant 5FU-based chemotherapy did not benefit older CRC patient, while neoadjuvant radiotherapy improved the prognosis of older patients with stage III rectal cancer.     

Adjuvante Therapie gastrointestinaler Tumoren

The aim of adjuvant therapy is to significantly lower the risk of a relapse and the development of distant metastases. Before adjuvant therapy is started it is obligatory to have carried out a complete staging as well as an informative consultation and an R0 situation. Because of conclusive study results neoadjuvant therapy has become the standard for rectal cancer and cancer of the upper gastrointestinal tract. In contrast to rectal cancer adjuvant therapy is the standard in colon cancer. While in Stadium I of colon cancer adjuvant therapy is not recommended, it is absolutely necessary in Stadium II with risk factors and in Stadium III. The best results are achieved with a regime of 5-FU-based chemotherapy in combination with oxaliplatin, whereas irinotecan, cetuximab and bevacizumab have no significance. In pancreatic carcinoma there is a suggestion for an adjuvant or rather additive therapy with gemcitabine. In the adjuvant therapy of gastrointestinal stromal tumors (GIST) imatinib is the standard therapy. The STORM study is investigating the effects of the multi-tyrosine kinase inhibitor sorafenib in the adjuvant setting of hepatocellular carcinoma.     

Adjuvant treatment for colorectal cancer.

Colorectal cancer is a leading cause of cancer in Western countries. Surgery remains the only way to cure it. Recent trials led to the general acceptance of adjuvant chemotherapy in Dukes C cancer by identifying bolus 5FU and leucovin during 6 months (5 days monthly) as the current standard. The role of adjuvant chemotherapy remains questionable in Dukes B2 (stage II) colon cancer, in rectal cancer and after curative resection of liver metastases. The development of total mesorectum excision (TME) technique has dramatically resulted in improving local recurrence control and will be the standard in rectal cancer surgery; preoperative irradiation is widely used in Europe for stage II and III rectal cancer but its definite place and its optimal regimen await further assessment as well as the role of adjuvant chemotherapy in rectal cancer. New chemotherapeutic combinations based on new effective agents in colorectal cancer such as CPT-11 and oxaliplatine have been currently used for downstaging liver metastases initially unresectable. This new approach, combined with the development of local ablative therapies such as cryotherapy and radiofrequency allows curative strategies in a significant number of patients primarily unfit for surgical resection of liver mets. The present paper aims to review the different aspect of (neo)adjuvant therapies in the multimodal curative management of colorectal cancers.     

Adjuvante Therapie des Kolonkarzinoms

Since its establishment 30 years ago, adjuvant chemotherapy for colon cancer has reduced the relapse rate and improved survival of patients after surgery. Adjuvant chemotherapy is therefore generally recommended in stage III tumors. By contrast, its benefit for stage II cancer in terms of survival benefit is questionable. The evaluation of various clinical trials identified factors that allow risk stratification for stage II. Accordingly, stage II colon cancer with microsatellite instability should be only followed up after curative surgery. Not only microsatellite instability, but also tumor location determine the prognosis of BRAF or KRAS mutant stage III. With the increasing knowledge on colon cancer, future developments will be directed towards a more stage-specific and individualized adjuvant therapy of colon cancer.     

Adjuvant therapy for stage II colorectal cancer: Who and with what?

Opinion statement The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-riskrd stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and metaanalyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-riskrd stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.     

Receipt of recommended therapy by patients with advanced colorectal cancer

OBJECTIVES: To evaluate utilization of surgery, chemotherapy, and radiation therapy among patients with stage II or III colon cancer and stage II/III rectal or rectosigmoid cancer, as recommended by current national guidelines. METHODS: This cross-sectional study at the Michael E. DeBakey Veterans Affairs Medical Center (Houston, TX) used 1999-2003 administrative data to identify patients with a diagnostic code for colorectal cancer. Medical charts were then abstracted to identify an incident cohort with stage II or III cancer. Outcome of interest was receipt of recommended therapy defined as surgery only (stage II colon) or surgery with adjuvant chemo- or radiotherapy (stage III colon or stage II/III rectal/rectosigmoid cancer). Potential determinants of receipt of recommended therapy were analyzed using logistic regression. RESULTS: Among 197 incident cases diagnosed or treated, mean age of patients was 66 yr (SD, 11 yr), 64% were Caucasian, and 98.5% were men. A gastroenterologist diagnosed 72.5% tumors including 62 stage II colon, 62 stage III colon, and 73 stage II/III rectal cancers. Referral to oncology occurred in 76% of stage II colon, 92% of stage III colon, and 99% of rectal cancers. 87% of stage II and 71% of stage III colon cancer patients received recommended therapy, compared to only 42.5% of rectal cancer patients. Predictors of receipt of recommended therapy among rectal cancers included being married (OR, 5.3; 95% CI: 1.6-17.1), presentation at tumor board (OR, 3.6; 95% CI: 1.2-11.2), or age<65 yr (OR, 3.5; 95% CI: 1.3-9.3). When patient's comorbidity and physician's decision-making process were considered in the assessment of the outcome, only presentation at tumor board remained predictive of receipt of recommended therapy. CONCLUSIONS: Most colon cancer patients at a major VA medical center receive recommended therapy. Among rectal cancer patients, those presented at tumor board are most likely to receive recommended therapy.     

Adjuvant therapies for colorectal cancer

The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced （stage M and selected stage 11） colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage 11 disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.     

Response to Preoperative Chemoradiation in Stage II and III Rectal Cancer

PURPOSE: The purpose of this study was to determine whether a complete pathologic response after neoadjuvant therapy in rectal cancer patients improves disease control and survival. METHODS: The study reviewed Stage II and III rectal cancer patients treated with preoperative chemoradiation and resected for cure. Complete pathologic response was defined as no cancer in the resected specimen. The main outcome measures were cancer-specific and disease-free survival in patients achieving a complete pathologic response and a noncomplete pathologic response. Kaplan-Meier curves were evaluated using log-rank analysis. RESULTS: Eighty-nine rectal cancer patients received neoadjuvant chemoradiation followed by radical resection for cure. Twenty-one patients (24 percent) achieved a complete pathologic response. Median follow-up for the complete pathologic response group was 23.5 months and 31 months for the noncomplete pathologic response group. There were more Stage III patients in the noncomplete pathologic response group than the complete pathologic response group (P = 0.005). Complete pathologic response patients were less likely to receive postoperative adjuvant chemotherapy than noncomplete pathologic response patients (P = 0.004). Cancer-specific and disease-free survival were not statistically different between the two groups. However, a trend was noted toward improved survival and decreased recurrence in association with a complete pathologic response. CONCLUSION: Stage III patients were less likely to be in the complete pathologic response group than Stage II patients. Complete pathologic response patients were less likely to receive postoperative adjuvant chemotherapy than noncomplete pathologic response patients. Complete pathologic response after neoadjuvant chemoradiation for rectal cancer patients demonstrated a trend toward improved survival and decreased recurrence compared with noncomplete pathologic response patients.     

Preliminary tolerance analysis of adjuvant chemotherapy in older patients after resection of stage III colon cancer from the PRODIGE 34-FFCD randomized trial

BackgroundColon adenocarcinoma mainly occurs in older patients. Oxaliplatin-based adjuvant chemotherapy improved disease-free survival after stage III colon cancer resection, but this improvement was not demonstrated in older patients.MethodsThe purpose of ADAGE-PRODIGE 34, randomized open phase III trial is to compare in patients over 70 years oxaliplatin plus fluoropyrimidine with fluoropyrimidine alone in fit patients (Group 1) and fluoropyrimidine with observation in frail patients (Group 2) after resection of stage III colon adenocarcinoma. We report a preliminary tolerance analysis on 50% of the first patients enrolled.ResultsThe analysis was conducted on 491 patients (378 in Group 1 and 113 in Group 2). Patients in Group 2 were older and showed more frailty criteria than those in Group 1. Cumulative grade 3–5 toxicities were more frequent in patients treated with oxaliplatin in Group 1 or with fluoropyrimidine in Group 2 than in patients treated with fluoropyrimidine in Group 1. At least one course was deferred in more than half of the patients in all groups. Early treatment cessation was more frequent in Group 2.ConclusionNo safety concerns were raised for the continuation of accrual. The frailty criteria distribution suggests that the investigator's evaluation for group allocation was accurate.     

Clinical experience with edrecolomab: a monoclonal antibody therapy for colorectal carcinoma

Edrecolomab (monoclonal antibody 17-1A) is a murine monoclonal antibody that recognizes the human tumor-associated antigen Ep-CAM (otherwise known as 17-1A). It is being developed for the adjuvant treatment of colorectal cancer. In a study of 189 patients with resected stage III colorectal cancer, treatment with edrecolomab resulted in a 32% increase in overall survival compared with no treatment (P<0.01) and decreased the tumor recurrence rate by 23% (P<0.04). In terms of safety, edrecolomab was well tolerated. Based on these study results, edrecolomab is currently under investigation in large multicenter phase III studies both as monotherapy and in combination with 5-fluorouracil-based chemotherapy versus chemotherapy alone for the treatment of stage III colon cancer. Although these studies are still ongoing, an interim analysis of safety data indicated that the combination of edrecolomab with chemotherapy is well tolerated. In addition, edrecolomab monotherapy demonstrated a favorable safety profile compared with chemotherapy. Edrecolomab is also currently being tested in large multicenter adjuvant phase III studies in stage II/III rectal cancer and stage II colon cancer. Edrecolomab represents a novel therapeutic approach and has the potential to become a treatment of choice as monotherapy in stage II colon cancer and in combination with chemotherapy in stage II/III rectal and stage III colon cancer.     

A Patient's Race/Ethnicity Does Not Explain the Underuse of Appropriate Adjuvant Therapy in Colorectal Cancer

Introduction To improve colorectal cancer outcomes, appropriate adjuvant therapy (chemotherapy, radiation therapy) should be given. Numerous studies have demonstrated underuse of adjuvant therapy in colorectal cancer. The current study examines variables associated with underuse of adjuvant therapy. Methods Three population-based databases were linked: California Cancer Registry, California Patient Discharge Database, 2000 Census. All colorectal cancer patients diagnosed from 1994 to 2001 were studied. Patient characteristics (age, gender, race/ethnicity, comorbidities, payer, diagnosis year, socioeconomic status) were used in five multivariate regression analyses to predict receipt of chemotherapy for Stage III colon cancer, and receipt of chemotherapy and radiation therapy for Stages II, III rectal cancer. Results The overall cohort was 18,649 Stage III colon cancer and Stages II, III rectal cancer patients. Mean age was 68.9 years, 50 percent male, 74 percent non-Hispanic white, 6 percent black, 11 percent Hispanic, 9 percent Asian, and 65 percent had no significant comorbid disease. Receipt of chemotherapy was 48 percent for Stage III colon cancer, 48 percent for Stage II rectal cancer, and 66 percent for Stage III rectal cancer. Receipt of radiation therapy was 52 percent for Stage II rectal cancer and 66 percent for Stage III rectal cancer. In all five models, low socioeconomic status predicted underuse of chemotherapy or radiation therapy (P < 0.016). Race/ethnicity was not statistically associated with underuse in any of the models. Conclusions Most literature identifies race/ethnicity as the reason for disparate receipt of adjuvant therapy in colorectal cancer. Using a more robust database of three population-based sources, our analysis demonstrates that socioeconomic status is a more important predictor of (in)appropriate care than race/ethnicity. Explicit measures to improve care to the poor with colorectal cancer are needed. Supported by Limited Project Grant from The American Society of Colon and Rectal Surgeons; Asian American Network for Cancer Awareness, Research, and Training Grant from the National Cancer Institute (#5U01CA086322-06); and the Robert Wood Johnson Clinical Scholars Program at UCLA. Read at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, April 30 to May 5, 2005; Recipient of the Piedmont Society of Colon and Rectal Surgeons Awards for Clinical Podium Presentation. Reprints are not available.     

Recurrence patterns after curative resection of colorectal cancer in patients followed for a minimum of ten years

BACKGROUND/AIMS: To investigate the recurrence patterns and interval from initial surgery in patients with curatively resected colorectal cancer followed for a minimum of 10 years. METHODOLOGY: We retrospectively reviewed 418 patients who had undergone curative resection for colon cancer (n = 246) or rectal cancer (n = 169). Follow-up periods ranged from 10 to 23 years. Main outcome measures were interval until recurrence, site of first recurrence, and influence of adjuvant chemotherapy. RESULTS: 26 (6%) had been lost to follow-up by 10 years and 143 (34%) had died. The most common site of recurrence was liver in colon cancer and locoregional in rectal cancer. The cumulative recurrence rate in colon cancer was 100% at 4 years. In rectal cancer, it was 89% at 5 years, 98% at 7 years and 100% at 10 years. The interval until recurrence was longer in rectal cancer (26.0 +/- 24.2 months) than in colon cancer (17.1 +/- 11.0 months) (p = 0.03). It was also longer in patients receiving than in those not receiving adjuvant chemotherapy (p < 0.01). The interval until lung metastasis was longer than that until liver metastasis in colon cancer (p = 0.04), and longer than that until locoregional recurrence in rectal cancer (p = 0.03). The interval until recurrence in the colon cancer was shorter for stage III than for stage II (p = 0.02). CONCLUSIONS: Surveillance for recurrences, particularly for relapses in the liver and lung, should be performed for at least 4 years in colon cancer patients. Patients with rectal cancer should be followed for a longer period than those with colon cancer, focusing on locoregional, liver and lung recurrence. It is particularly noteworthy that adjuvant chemotherapy may prolong the interval until recurrence and the interval until lung metastasis is relatively longer.     

Is there a role for adjuvant chemotherapy in pathological complete response rectal cancer tumors following neoadjuvant chemoradiotherapy?

Purpose

To investigate the contribution of neoadjuvant chemotherapy in rectal cancer patients with pathological complete response (pCR).

Methods

Data were collected on all consecutive locally advanced rectal cancer patients treated with neoadjuvant chemotherapy and later resected in our institution between 2001 and 2013. Surgery was performed by a single proctology team, and tumor specimens were evaluated by the hospital pathologists.

Results

The medical records of 260 patients were analyzed, and 54 patients of those patients were found to have achieved pCR (20.8 %). Two of those patients were lost to follow-up. Thirty-five of the 54 pCR patients received adjuvant chemotherapy (Group A) and 17 did not (Group B). With the sole exception of the Group A patients being younger than the Group B patients (60.9 ± 11.9 vs. 68.7 ± 10.8 years, respectively, p = 0.0272), all other evaluated parameters were identical between the two groups. There was no advantage for the administration of adjuvant chemotherapy for disease-free survival (DFS) and overall survival (OS).

Conclusions

Adjuvant chemotherapy played no part in disease-free survival and OS of patients with rectal cancer who had been treated with neoadjuvant chemotherapy and achieved pCR. Our findings indicate a tendency for adjuvant chemotherapy to be administered to younger rectal cancer patients. A randomized trial should be conducted to resolve the question of whether they derive any benefit from it.     

Multi-modality treatment of colorectal liver metastases

Liver metastases synchronously or metachronously occur in approximately 50% of colorectal cancer patients. Multimodality comprehensive treatment is the best therapeutic strategy for these patients. However, the optimal pattern of multimodality therapy is still controversial, and it raises several significant concerns. Liver resection is the most important treatment for colorectal liver metastases. The definition of resectability has shifted to focus on the completion of R0 resection and normal liver function maintenance. The role of neoadjuvant and adjuvant chemotherapy still needs to be clarified. The management of either progression or complete remission during neoadjuvant chemotherapy is challenging. The optimal sequencing of surgery and chemotherapy in synchronous colorectal liver metastases patients is still unclear. Conversional chemotherapy, portal vein embolization, two-stage resection, and tumor ablation are effective approaches to improve resectability for initially unresectable patients. Several technical issues and concerns related to these methods need to be further explored. For patients with definitely unresectable liver disease, the necessity of resecting the primary tumor is still debatable, and evaluating and predicting the efficacy of targeted therapy deserve further investigation. This review discusses different patterns and important concerns of multidisciplinary treatment of colorectal liver metastases.     

结肠癌围手术期治疗进展

结肠癌术后辅助化疗特别是氟尿嘧啶类联合奥沙利铂化疗已明显降低结肠癌术后的复发转移,成为Ⅱ和Ⅲ期患者的标准治疗方法。随着外科技术和理念的更新以及对肿瘤生物学特别是分子标记物认识的深入,辅助化疗的个体化和分层治疗策略成为了研究热点,同时新辅助治疗模式在直肠癌中的成功也使结肠癌新辅助化疗日渐受到关注。本文将梳理最新结肠癌复发、治疗风险评估和围手术期治疗进展,以协助临床医生更好地理解结肠癌的个体化治疗并运用于临床工作中。     

Prognostic factors in Stage T2NO rectal cancer

PURPOSE: To further define the indications for postoperative pelvic irradiation and chemotherapy, an analysis of the influence of extent of tumor invasion into perirectal fat, lymphatic or venous vessel invasion, and tumor grade on the clinical course of patients with Stage T2NO rectal cancer undergoing surgery was undertaken. METHODS: From 1968 to 1985, 117 patients with Stage T3NO rectal cancer underwent resection with curative intent. No patient received neoadjuvant or adjuvant irradiation or chemotherapy. Surgical specimens were assessed for maximum depth of tumor invasion into perirectal fat, lymphatic or venous involvement, and tumor grade. After surgery the clinical course of these patients was assessed for local control, distant metastases, and survival rate. RESULTS: For 25 patients with tumors exhibiting favorable histologic features (well-differentiated or moderately well-differentiated carcinomas invading less than 2 mm into perirectal fat, without lymphatic or venous vessel involvement), the ten-year actuarial rates of local control and recurrence-free survival were 95 and 87 percent, respectively. In contrast, the ten-year actuarial rates of local control and recurrence-free survival were inferior (71 and 55 percent, respectively) for 88 patients with tumors exhibiting moderate to deep perirectal fat invasion, vessel involvement, or poor differentiation. CONCLUSIONS: In the design of future trials of rectal cancer, selection of patients with rectal cancer for postoperative adjuvant therapy should be based not only on stage, but also on depth of invasion into the perirectal fat, vessel involvement, tumor grade, and integrity of the radial resection margin. For subsets of patients with Stage T3NO rectal cancer, there may be little benefit to adjuvant therapy after surgery.     

Adjuvant therapy for colorectal cancer

In recent years, adjuvant therapy for colorectal cancer has advanced considerably. This article reviews these advances and provides an update of the most recent and ongoing trials. In 1990, adjuvant therapy became the “standard of care” for patients with Stage III colon cancer (Dukes C) in the United States. Recent clinical trial data indicate that adjuvant treatment may also be effective in patients with Stage II (Dukes B₂) colon cancer. The combination of 5-fluorouracil plus leucovorin may slightly improve survival (5–10 percent) compared with the standard 5-fluorouracil plus levamisole combination. The three-drug regimen (5-fluorouracil plus levamisole plus leucovorin) is more toxic, with no superior effect on survival. Intraportal chemotherapy, although it may significantly improve patient survival, does not decrease the frequency of liver metastases. However, it is still a promising form of adjuvant therapy owing to its short treatment period and relatively equivalent effects in survival compared with that of systemic therapy. For patients with Stage II or Stage III rectal cancer, postoperative systemic 5-fluorouracil plus radiation therapy plus protracted venous 5-fluorouracil infusion is the most effective postoperative adjuvant regimen. However, results from several studies show that preoperative radiation alone or chemoradiation for advanced local rectal cancers might also be effective while also improving resectability, decreasing morbidity, and increasing the chance that a sphincter-sparing procedure may be performed. The role of leucovorin in rectal cancer remains to be determined. Immune therapies with agents such as interferon-α-2a, monoclonal antibody 17-1A, and autologous tumor vaccines are being assessed and could further improve survival.     

Postoperative management of stage II/III colon cancer: a decision analysis.

BACKGROUND & AIMS: Two separate decisions must be made for the management of patients with resected stage II/III colon cancer: whether to begin adjuvant chemotherapy and whether patients should be included in a follow-up protocol consisting of regular monitoring of carcinoembryonic antigen level and of colonoscopy and imaging. The standard management for these patients is adjuvant chemotherapy for stage III patients and follow-up for stage II/III patients with resected colon cancer. METHODS: Decision analysis was used to compare the effectiveness (5-year survival rate) and cost-effectiveness ratio of 7 strategies of treatment and follow-up. RESULTS: The most cost-effective strategies were adjuvant chemotherapy for all patients with stage II/III resected colon cancer, with either no follow-up or follow-up only for patients aged less than 75 years with a seric preoperative carcinoembryonic antigen level of >5 ng/mL (5-year survival, 62.3% or 62.7%; cost per surviving patient, $8254 or $8657, respectively). The order of efficacy of the strategies was insensitive to changes in the values of the studied variables. The method of follow-up does little to improve 5-year survival but adds substantial cost. CONCLUSIONS: The current standard strategy may not be the most cost-effective strategy for the management of patients with resected colon cancer.