IIIA Colon Cancer Research Articles

From Evidence-based Medicine to Personalized Medicine

See Article on Page 259-264 Over the last two decades, many studies have shown the role of the adjuvant chemotherapy in stage III colon cancer [1-8]. With the introduction of excellent cytotoxic agents such as oxaliplatin and irinotecan, the median survival of even stag IV disease has been prolonged by more than 24 months. Based on the National Comprehensive Cancer Network (NCCN) guideline and the recently published Korean guideline, the oxaliplatin-based regimen has been the preferred regimen for stage III colon cancer over a single-agent regimen such as the capecitabine or 5-fluorouracil/leucovorin (FL) regimen. However, some concerns exist regarding the toxicity and the efficacy in adjuvant chemotherapy for stage III colon cancer. Because adjuvant chemotherapy means largely prophylactic chemotherapy rather than therapeutic chemotherapy like palliative chemotherapy, the efficacy of adjuvant chemotherapy should be balanced with its possible side effects, such as peripheral neuropathy or febrile neutropenia. For many years, the ideal duration of adjuvant chemotherapy has been under evaluation. Particularly with regard to the cumulative neuropathic adverse effects of oxaliplatin, a further decrease in the treatment duration is warranted. The SAFFA study showed no differences in term of overall survival between six months of a bolus FL regimen or three months of a protracted FL regimen [3]. However, a shorter adjuvant treatment duration is currently under evaluation in the IDEA program, which includes 12,000 patients from six ongoing trials [9]. Recently, the elderly population has grown remarkably worldwide. South Korea is also one of the countries with a fast-growing elderly population. The subgroup analysis of the NSABP C-07 trial showed a trend towards better disease-free survival in patients younger than age 70 (hazard ratio, 0.80; 95% confidence interval, 0.68 to 0.95; P = 0.013), but no positive effect was evident in older patients with the addition of oxaliplatin to the FL regimen [10]. Even the NCCN guideline recommended that the oxaliplatin-based regimen not be used for elderly patients older than 70 years. Conversely, capecitabine showed a constant efficacy even in elderly patients [11]. Lymph node metastasis is the single most important prognostic factor in colon cancer. It also determines the necessity of adjuvant chemotherapy in colon cancer. In the 7th American Joint Committee on Cancer tumor-node-metastasis staging system [12], the 5-year survival of stage IIIA colon cancer was even better than that of stage IIA colon cancer, which raised the concerns about the necessity of and ideal regimen for adjuvant chemotherapy in stage IIIA colon cancer. In this issue of the Journal of the Korean Society of Coloproctology, an article entitled Oncologic Outcome of Stage IIIA Colon Cancer According to Chemotherapeutic Regimen dealt with this specific concern. Although the study was a single-institution-based retrospective review and included a relatively small number of patients (n = 131) to draw a concrete conclusion, single-agent-based chemotherapeutic regimens (capecitabine or FL) showed 5-year disease free and overall survival rates similar to those of oxaliplatin-based regimens. In stage IIIA colon cancer, the depth of invasion is limited to the muscularis propria, and lymph node metastases are minimal (up to 6 metastatic lymph nodes). Among the eight patients who did not receive the adjuvant chemotherapy, three patients had recurrences during the follow-up, which suggested that adjuvant chemotherapy has a role even in stage IIIA colon cancer. This study suggested the need for further clinical trials in Korea to obtain solid evidence for this specific condition. The incidence of stage IIIA disease is very low, so it takes a long time to collect the patients to identify effective chemotherapeutic agents as in this paper (from 1995 to 2008, only 131 patients were collected). During that time in Korea, the governmental insurance policies changed continuously, so it was hard to measure the real value of the different regimens of adjuvant chemotherapeutic agents. However, this study provides possible clues for individualized or personalized chemotherapy. In the near future, I hope the Korean Society of Coloproctology may have a role in addressing this specific question.

Compliance and Effective Management of the Hand-Foot Syndrome in Colon Cancer Patients Receiving Capecitabine as Adjuvant Chemotherapy

PurposePhysicians and oncology nurses must continue to update their knowledge on treatment and treatment-related side effects, while searching for effective methods to prevent or manage side effects. The objective of our study was to describe the incidence and response to treatment of the hand-foot syndrome (HFS) and the compliance with treatment of patients with stage IIB, IIIA, IIIB, and IIIC colon cancer that were treated with capecitabine alone as adjuvant therapy.Materials and MethodsBetween September 2005 and September 2006, 84 patients fulfilled the inclusion criteria and were included in this retrospective analysis of prospectively collected data.ResultsThe treatment compliance rate was 90.5% (76 out of the 84 patients). The HFS developed in 65 patients (77.4%). Thirty-three patients (50.7%) had grade 1 HFS, 22 patients (33.8%) had grade 2 HFS and 10 patients (15.5%) had grade 3 HFS, as their most severe episode. For Grade 1 patients, the dose was maintained, and skin barrier cream and moist exposed burn ointment (MEBO) were applied. For Grade 2 patients, either the dose was maintained or 25% of the dose was reduced; MEBO and supportive care were provided. For Grade 3 patients, one cycle of chemotherapy was interrupted followed by dose adjustment; MEBO and supportive care were provided.ConclusionHFS is manageable if both patients and oncology care teams are educated about HFS associated with capecitabine. The HFS is treated by patient education, preventive management, ointment application, conservative management, dose reduction, and interruption of chemotherapy administration.

Oral Mucositis

Ms. J is a 55-year-old woman who was diagnosed with stage IIIA colon cancer three months ago. Prior to her diagnosis, she experienced an unintentional 17-pound weight loss. She underwent an exploratory laparotomy with colon resection. Following recovery from her surgery, she began an adjuvant chemotherapy regimen of 5-fluorouracil, leucovorin, and oxaliplatin. She presents to the clinic today for her third chemotherapy treatment.

Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging.

The recently revised American Joint Committee on Cancer (AJCC) sixth edition cancer staging system increased the stratification within colon cancer stages II and III defined by the AJCC fifth edition system. Using nationally representative Surveillance, Epidemiology, and End Results (SEER) data, we compared survival rates associated with colon cancer stages defined according to both AJCC systems. Using SEER data (from January 1, 1991, through December 31, 2000), we identified 119,363 patients with colon adenocarcinoma and included all patients in two analyses by stages defined by AJCC fifth and sixth edition systems. Tumors were stratified by SEER's "extent of disease" and "number of positive [lymph] nodes" coding schemes. Kaplan-Meier analyses were used to compare overall and stage-specific 5-year survival. All statistical tests were two-sided. Overall 5-year survival was 65.2%. According to stages defined by the AJCC fifth edition system, 5-year stage-specific survivals were 93.2% for stage I, 82.5% for stage II, 59.5% for stage III, and 8.1% for stage IV. According to stages defined by the AJCC sixth edition system, 5-year stage-specific survivals were 93.2% for stage I, 84.7% for stage IIa, 72.2% for stage IIb, 83.4% for stage IIIa, 64.1% for stage IIIb, 44.3% for stage IIIc, and 8.1% for stage IV. Under the sixth edition system, 5-year survival was statistically significantly better for patients with stage IIIa colon cancer (83.4%) than for patients with stage IIb disease (72.2%) (P<.001). The AJCC sixth edition system for colon cancer stratifies survival more distinctly than the fifth edition system by providing more substages. The association of stage IIIa colon cancer with statistically significantly better survival than stage IIb in the new system may reflect current clinical practice, in which stage III patients receive chemotherapy but stage II patients generally do not.