The last several years have major advances in chemotherapy treatment for adjuvant and metastatic colorectal cancer. We've come from an overall survival of 6 months in patients treated with best supportive care in the mid 1980s and even in the early 1990s. The use of 5-FU/leucovorin alone generates an overall survival of about 6 months. The addition of irinotecan/oxaliplatin allows patients to live a median of about 15 to 17 months. If we make use of all 3 active drugs, FOLFOX and FOLFIRI in a sequential manner, we'll be able to generate an overall survival of about 20 months. Recently, the addition of molecular therapy, in particular bevacizumab and cetuximab to these cytotoxic drugs has allowed us to break the brick wall that was placed at about 2 years median overall survival in large phase 3 trials in patients with metastatic colorectal cancer. The recent presentations provided further evidence that the standard of care in the treatment of advanced CRC consists of a combination of highly active cytotoxic chemotherapy plus the addition of a biologic agents, For clinical research, investigation of the best therapy for CRC has clearly shifted away from investigating conventional chemotherapy toward the question of how to make best use of all available active agents, particularly the novel biologics. Randomized trials have also shown that preoperative chemoradiation yields higher rates of pathologic complete response and local control, compared with radiotherapy alone. In this article, I review recent trials on preoperative and adjuvant therapy of localized rectal cancer. The roles of newer agents, such as capecitabine, oxaliplatin, and bevacizumab, are also discussed, and other key issues in the treatment of localized rectal cancer are reviewed. The planned phase 3 first-line trial will continue to elucidate the role of the currently available biologics in the treatment of CRC. In this article, the important advances in optimal chemotherapy of colorectal cancer will be summarized and approaches to multidisciplinary treatment decision-making in both adjuvant and metastatic settings will be reviewd.
Biological Factors ; Biological Products ; Colorectal Neoplasms* ; Drug Therapy* ; Humans ; Radiotherapy ; Rectal Neoplasms ; Standard of Care ; Bevacizumab ; Capecitabine ; Cetuximab

PURPOSE: This study was designed to analyze the clinical characteristics of patients with immediate distant metastasis after preoperative chemoradiotherapy for locally advanced rectal cancer and to help select patients for preoperative chemoradiotherapy. METHODS: Two hundred eight patients, who underwent preoperative chemoradiotherapy for locally advanced rectal cancer, were included. Patients were excluded from the study if they had tumor types other than an adenocarcinoma, prior chemotherapy, radiotherapy, or hereditary nonpolyposis colorectal cancer. The clinicopathological characteristics of patients with distant metastasis immediately after preoperative chemoradioterapy were compared with those of patients without distant metastasis. RESULTS: Distant metastases immediately after preoperative chemoradiotherapy were identified in 15 patients (7.2%). The liver was the most common site of metastasis (8/15), followed by peritoneal seeding (4), the lung (2), bone (1), and the aortocaval lymph node (1). Age, sex, chemotherapy regimen used, and primary tumor response for patients with distant metastases were similar to those for patients without distant metastasis. In patients with immediate distant metastasis, pre-chemoradiotherapy CEA was significantly higher (11.1 vs. 7.4 ng/ml; P= 0.003). CONCLUSIONS: Immediate distant metastasis after preoperative chemoradiotherapy is associated with pre-chemoradiotherapy CEA level. A careful work-up is necessary when pre-chemoradiotherapy CEA is higher than the normal range.
Adenocarcinoma ; Chemoradiotherapy* ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Drug Therapy ; Humans ; Liver ; Lung ; Lymph Nodes ; Neoplasm Metastasis* ; Radiotherapy ; Rectal Neoplasms* ; Reference Values

5-Fluorouracil (5-FU) has been the main chemotherapeutic agent for the treatment of colorectal cancer for four decades with modest efficacy. Modulation of 5-FU by leucovorin or continuous infusion improves the response rate, but overall survival duration remains approximately 12 months. Many oral fluoropyrimidines have been studied, including capecitabine, UFT, S-1, and Eniluracil. Capecitabine has demonstrated equivalent efficacy with 5-FU and has been approved as first line treatment. CPT-11 demonstrated non-crossover resistance with 5-FU and was proven to be effective treatment for patients who received prior 5-FU. CPT-11 in combination with 5-FU has demonstrated improved response rate and overall survival duration over 5-FU or CPT-11. Oxaliplatin plus 5-FU has offered another effective treatment option for colorectal cancer. Both 5-FU plus leucovorin in combination with CPT-11 or oxaliplatin are widely used first-line chemotherapies for advanced colorectal cancer. The combinations of capecitabine with CPT-11 or oxaliplatin are being developed. Several molecular targeting agents such as EGFR inhibitors and antiangiogenic agents have developed. Cetuximab induces a broad range of cellular responses in tumors expressing EGFR, enhancing sensitivity to radiotherapy and chemotherapeutic agents. A key angiogenic pathway in the stimulation of tumour growth is the vascular endothelial growth factor (VEGF) pathway, inhibited by the monoclonal antibody bevacizumab. Phase II first line and phase III second line studies of oxaliplatin in combination with bevacizumab are now in progress. Optimal combinations and sequences of treatment are being studied, since several effective regimens have become available.
Angiogenesis Inhibitors ; Colorectal Neoplasms* ; Drug Therapy* ; Fluorouracil ; Humans ; Leucovorin ; Radiotherapy ; Vascular Endothelial Growth Factor A ; Bevacizumab ; Capecitabine ; Cetuximab

PURPOSE: In Korea, colorectal cancer (CRC) is one of the most sharply-increasing malignancies, and the National Colorectal Cancer Screening Program for persons over 50 years of age began in 2004. To determine the effectiveness of the program, comparative data regarding CRCs treated prior to 2004 must be analyzed. The present study assessed CRC status at diagnosis and treatment patterns in 2003. METHODS: In 2003, 503 patients were newly diagnosed with CRC and were treated at the Center for Colorectal Cancer, National Cancer Center (NCC). Clinical data were retrospectively reviewed. RESULTS: The 503 patients included 256 colon and 247 rectal cancer patients. Of the 256 colon cancer patients, 5 (2.0%) were diagnosed during screening colonoscopies and were successfully treated using an endoscopic mucosal resection (EMR), and 17 (6.6%) received only palliative chemotherapy because of distant metastases. Forty patients (15.6%) were treated with palliative surgery and chemotherapy, and 194 (75.8%) with curative surgery with or without adjuvant chemotherapy. Of the 247 rectal cancer patients, 9 (3.6%) were treated with an EMR, 20 (8.1%) with palliative chemotherapy with or without radiotherapy, 19 (7.7%) with palliative surgery and chemoradiotherapy, and 199 (80.6%) with curative surgery with or without chemoradiotherapy. Treatment with curative intent was possible in 199 of 256 (77.7%) colon cancer patients and in 208 of 247 (84.2%) rectal cancer patients. CONCLUSIONS: Only 12.1% of colon and 8.5% of rectal cancer patients were diagnosed early and treated without adjuvant therapies at the NCC in Korea in 2003.
Chemoradiotherapy ; Chemotherapy, Adjuvant ; Colon ; Colonic Neoplasms ; Colonoscopy ; Colorectal Neoplasms* ; Diagnosis ; Drug Therapy ; Humans ; Korea* ; Mass Screening ; Neoplasm Metastasis ; Palliative Care ; Radiotherapy ; Rectal Neoplasms ; Retrospective Studies

The colorectal cancer frequently metastasizes to the liver, lung, peritoneum, bone, ovaries, and the adrenal glands. Neck metastasis from colorectal carcinoma, however, is extremely rare. We experienced a case of rectal cancer presenting with neck metastasis. The patient was a 45-year-old man who underwent pre-operative chemotherapy and radiotherapy, and low anterior resection with loop T-colostomy for adenocarcinoma of rectum. Six months later, he presented with palpable mass on the left neck, which progressively increased in size. CT scan showed a 4 X 3.5 X 2.5 cm-sized mass on the level III, IVB of left neck with sternocleidomastoid muscle infiltration. There was no evidence of distant metastasis. But biopsy of the mass revealed metastatic adenocarcinoma, and the histologic findings were similar to that of the primary rectal adenocarcinoma. We present this case of neck metastasis from rectal adenocarcinoma, with the review of literature.
Adenocarcinoma ; Adrenal Glands ; Biopsy ; Colorectal Neoplasms ; Drug Therapy ; Female ; Humans ; Liver ; Lung ; Middle Aged ; Neck* ; Neoplasm Metastasis* ; Ovary ; Peritoneum ; Radiotherapy ; Rectal Neoplasms* ; Rectum ; Tomography, X-Ray Computed

PURPOSE: To investigate the treatment outcome and the toxicity of helical tomotherapy (HT) in patients with metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: We retrospectively reviewed 18 patients with 31 lesions from mCRC treated with HT between 2009 and 2013. The liver (9 lesions) and lymph nodes (9 lesions) were the most frequent sites. The planning target volume (PTV) ranged from 12 to 1,110 mL (median, 114 mL). The total doses ranged from 30 to 70 Gy in 10-30 fractions. When the alpha/beta value for the tumor was assumed to be 10 Gy for the biologically equivalent dose (BED), the total doses ranged from 39 to 119 Gy10 (median, 55 Gy10). Nineteen lesions were treated with concurrent chemotherapy (CCRT). RESULTS: With a median follow-up time of 16 months, the median overall survival for 18 patients was 33 months. Eight lesions (26%) achieved complete response. The 1- and 3-year local progression free survival (LPFS) rates for 31 lesions were 45% and 34%, respectively. On univariate analysis, significant parameters influencing LPFS rates were chemotherapy response before HT, aim of HT, CCRT, PTV, BED, and adjuvant chemotherapy. On multivariate analysis, PTV < or =113 mL and BED >48 Gy10 were associated with a statistically significant improvement in LFPS. During HT, four patients experienced grade 3 hematologic toxicities, each of whom had also received CCRT. CONCLUSION: The current study demonstrates the efficacy and tolerability of HT for mCRC. To define optimal RT dose according to tumor size of mCRC, further study should be needed.
Chemotherapy, Adjuvant ; Colorectal Neoplasms* ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Liver ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Radiotherapy, Intensity-Modulated* ; Retrospective Studies ; Treatment Outcome

BACKGROUND: Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. METHODS: Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. RESULTS: SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151). CONCLUSIONS: Findings suggested that multiplicity of advanced T category–tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer's tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.
Adenomatous Polyposis Coli ; Chemotherapy, Adjuvant ; Colorectal Neoplasms ; CpG Islands ; Drug Therapy ; Humans ; Joints ; Microsatellite Instability ; Neoplasm Metastasis ; Phenotype ; Radiotherapy ; Risk Factors

Intramedullary spinal cord metastasis (ISCM) is an uncommon condition of the central nervous system (CNS) cause by systemic malignant tumors. Most ISCM cases are known to occur in patients with lung cancer and breast cancer; however, ISCM also very rarely occurs in patients with colorectal cancer. For the first time in Korea, we experienced a case of ISCM arising from rectal cancer, where a 75-year-old man presented with an abruptly-developed left-foot drop and numbness in both legs. The patient had lung metastases from rectal cancer that had been treated with chemotherapy. Magnetic resonance imaging revealed an intramedullary nodular lesion at the T12 level. ISCM was diagnosed and treated with steroids and radiotherapy. The patient's neurological symptoms were relieved for a while after treatment, but his condition deteriorated progressively. He died 4 months after ISCM had been diagnosed.
Aged ; Breast Neoplasms ; Central Nervous System ; Colorectal Neoplasms ; Drug Therapy ; Humans ; Hypesthesia ; Korea ; Leg ; Lung ; Lung Neoplasms ; Magnetic Resonance Imaging ; Neoplasm Metastasis* ; Radiotherapy ; Rectal Neoplasms* ; Spinal Cord Neoplasms ; Spinal Cord* ; Steroids

Individualized tailored therapy is a currently pursuing direction for improving the outcome of patients with colorectal cancer. Targeted therapy is the potential strategy to reach this goal by evaluating status of the presumed targets and their related effector molecules and by maximizing the efficacy of chemotherapeutic agents with less toxicity in individual patient. Numerous hurdles should be overcome, however, because therapeutic outcome can be affected by multiple components; tumor characteristics such as somatic mutations at the DNA, RNA, and protein levels; patient characteristics like germline genetic polymorphisms in enzymes linked to drug metabolism; and environmental factors that include diet and physical activity. Currently, large numbers of potential biomarkers have been proposed but have not yet accomplished supporting evidences for their routine usage in clinics. Therefore, clinical trials driven by molecular targets and relevant biomarkers for the understanding of the conflicting data are needed to make markers available in clinical practice.
Colorectal Neoplasms/*drug therapy/radiotherapy ; Combined Modality Therapy ; CpG Islands/genetics ; DNA Topoisomerases, Type I/genetics ; Humans ; Receptor, Epidermal Growth Factor/genetics ; Thymidylate Synthase/genetics ; Tumor Markers, Biological/*genetics

OBJECTIVETo investigate the clinical features and prognosis of bone metastases in colorectal cancer patients.

METHODSThe clinical data of 104 cases of colorectal cancer with bone metastasis were collected and retrospectively analyzed.

RESULTSAmong all the 104 patients included, 45 (43.3%) patients had multiple bone metastases, and 59 (56.7%) patients had single bone metastasis. Pelvis (46.1%) was the most common site, followed by thoracic vertebrae (41.3%), lumbar vertebrae (40.4%), sacral vertebrae (29.8%) and ribs (29.8%). One hundred and two patients (98.1%) were complicated with other organ metastases. The median time from colorectal cancer diagnosis to bone metastasis was 16 months, and the median time from bone metastasis to first skeletal-related events (SREs) was 1 month. The most common skeletal-related events (SREs) were the need for radiotherapy (44.2%), severe bone pain (15.4%) and pathologic fracture (9.6%). The median survival time of patients with bone metastases was 10.0 months, and 8.5 months for patients with SREs. ECOG score, systemic chemotherapy and bisphosphonate therapy were prognostic factors by univariate analysis (all P < 0.05). ECOG score and systemic chemotherapy were independent prognostic factors by Cox multivariate analysis.

CONCLUSIONSBone metastasis in colorectal cancer patients has a poor prognosis and the use of chemotherapy and bisphosphonates may have a benefit for their survival.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Density Conservation Agents ; therapeutic use ; Bone Neoplasms ; drug therapy ; radiotherapy ; secondary ; Colorectal Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Diphosphonates ; therapeutic use ; Female ; Follow-Up Studies ; Fractures, Bone ; etiology ; Humans ; Lumbar Vertebrae ; pathology ; Male ; Middle Aged ; Pain ; etiology ; Pelvic Bones ; pathology ; Prognosis ; Retrospective Studies ; Ribs ; pathology ; Sacrum ; pathology ; Spinal Cord Compression ; etiology ; Spinal Neoplasms ; drug therapy ; radiotherapy ; secondary ; Thoracic Vertebrae ; pathology ; Young Adult