Colorectal cancer (CRC) is the third most common cancer and second leading cause of death from cancer in North America. The authors provide an overview of the indications for both chemotherapy and targeted therapy, as well as discuss the efficacy and toxicity of systemic therapy. They highlight the key studies that lead to the initial historical use of fluorouracil (5FU) based chemotherapy in the adjuvant and metastatic setting, the recent adoption of 5FU plus leucovorin (LV) and oxaliplatin (FOLFOX) chemotherapy over 5FU when treating adjuvant patients, and the use of FOLFOX or 5FU plus LV and irinotecan (FOLFIRI) in metastatic patients. They also review the role of chemotherapy in treating rectal cancer and resectable liver metastatic disease. Future areas of research focus for systemic therapy of colorectal cancer are highlighted.

A standard therapy for locally advanced rectal cancer (LARC) includes fluoropyrimidine (FP)-based neoadjuvant chemoradiation (nCRT). Previous studies have inconsistently demonstrated that baseline neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR) are predictive of response to nCRT or prognostic of outcomes in LARC. We reviewed patients with LARC undergoing nCRT followed by surgery from 2005 to 2013 across 8 Canadian cancer centres. Outcome measures of interest were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for associations between baseline hematologic variables and outcomes. Of 1527 identified patients, 1237 (81%) were included in the DFS/OS analysis. Median age was 62 (range 23–88), 69% were male, and 80% had performance status (PS) 0–1. Twenty-six percent had elevated NLR (≥ 4), and 66% had elevated PLR (≥ 150). Ninety-seven percent of patients received FP-based nCRT, with 96% receiving ≥44 Gy. 81% completed neoadjuvant chemotherapy and 95% completed neoadjuvant radiotherapy, with a pCR rate of 18%. After a median follow-up time of 71 months, 8% developed local recurrence, 22% developed distant recurrence and 24% died. 5-year DFS and OS were 69% (95% CI 66–72%) and 79% (95% CI 77–82%), respectively. In multivariate analyses, elevated baseline NLR and PLR were neither prognostic for DFS and OS nor predictive of pCR. NLR and PLR were not found to be independently prognostic for DFS or OS and did not predict for pCR in patients with LARC undergoing nCRT followed by surgery.

Background: The interplay between comorbidity, age and performance status (PS) as predictors of outcome in advanced colorectal cancer (ACRC) is poorly understood. We examined these factors as predictors of treatment toxicity and outcome in cetuximab-treated patients with ACRC. Patients and methods: Comorbidity was independently evaluated using the Charlson Comorbidity Index (CCI), a validated measure of comorbidity based on the presence of medical conditions weighted according to their effect on mortality. CCI score was correlated with clinical and outcome data. Results: Five hundred and seventy-two patients were included; 41% were ≥65 years and 25% had comorbidities at randomization. In multivariate analysis (MVA) of all covariates, only older age was associated with greater comorbidity (P = 0.008). Overall survival (OS) was significantly better for patients with greater comorbidity in univariate analysis (P = 0.047). Conversely, better PS was associated with better OS in MVA (hazard ratio 1.92 for PS = 2 versus PS = 0, P < 0.0001). Age was not associated with OS (P = 0.13). Elderly patients had significantly less grade ≥3 vomiting (P = 0.034) but more dyspnea (P = 0.005). Patients with greater comorbidity had significantly less grade ≥3 vomiting (P = 0.002) but more non-neutropenic fever (P = 0.005). Conclusion: Better PS was associated with improved OS. For patients with good PS, restricting cetuximab use in the setting of significant comorbidity does not appear justified.

Background Before the emergence of first-line combination chemotherapy, the standard of care for unresectable metastatic colorectal cancer (mcrc) was first-line monotherapy with modulated 5-fluorouracil. Several large phase iii randomized controlled trials, now completed, have assessed whether a planned sequential chemotherapy strategy—beginning with fluoropyrimidine monotherapy until treatment failure, followed by another regimen (either monotherapy or combination chemotherapy) until treatment failure—could result in the same survival benefit produced with an upfront combination chemotherapy strategy, but with less toxicity for patients. Methods The medline and embase databases, and abstracts from meetings of the American Society for Clinical Oncology and the European Society for Medical Oncology, were searched for reports comparing a sequential strategy of chemotherapy with an upfront combination chemotherapy in adult patients with mcrc. Publications that reported efficacy or toxicity data (or both) were included. Results The five eligible trials that were identified included 4532 patients. A meta-analysis of those trials demonstrates a statistically significant survival advantage for combination chemotherapy (hazard ratio: 0.92; 95% confidence interval: 0.86 to 0.99). However, the median survival advantage (3–6 weeks in most trials) is small and of questionable clinical significance. Three trials reported first-line toxicities. Upfront combination chemotherapy results in significantly more neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, nausea, vomiting, and sensory neuropathy. Sequential chemotherapy results in significantly more hand–foot syndrome. Conclusions Given the small survival advantage associated with upfront combination chemotherapy, planned sequential chemotherapy and upfront combination chemotherapy can both be considered treatment strategies. Treatment should be chosen on an individual basis considering patient and tumour characteristics, toxicity of each strategy, and patient preference.

Background: Cancer is a health concern in Inuit populations. Unique cultural, dietary, and genetic factors and geographic isolation influence cancer epidemiology in this group. Inuit-specific data about oncology treatments and survival outcomes in Canadian Inuit referred to urban treatment centres are lacking. Methods: A retrospective chart review of Inuit patients referred to The Ottawa Hospital Cancer Centre (TOHCC) from the Baffin region of Nunavut between 2000 and 2010 was conducted. Nunavut cancer registry data were used to establish the percentage of cancer cases referred and their survival outcomes. Results: Of 307 cancer patients registered among Baffin-region Inuit, 216 [70% (63 men, 153 women)] were referred to TOHCC for chemotherapy (CT) and radiation therapy (RT). Mean age in the referred group was 59.3 years (range: 25–89 years), and current smokers constituted half the group (52%). The cancers most commonly leading to referral in men were lung (55%), colorectal (19%), and nasopharyngeal (11%) cancers; in women, they were lung (46%), colorectal (24%), breast (10%), nasopharyngeal (6%), and cervical (5%) cancers. Of the 216 referred patients, 82 (38%) had already undergone surgery, and 18 (8%) received chemoradiation or RT only, all given with curative intent. Among the surgical patients referred, 33 (40%) and 23 (28%) went on to receive adjuvant CT and adjuvant RT respectively. Among 116 patients referred for palliative care, 64 (55%) received CT, 76 (66%) received RT, 43 (37%) received both CT and RT, and 19 (16%) received neither treatment. Median all-stage overall survival was 10 months for patients with lung cancer [95% confidence interval: 6.1 to 13.9 months] and 37 months for patients with colorectal cancer [95% confidence interval: 14.8 to 59.2 months]. Conclusions: High uptake of palliative and adjuvant CT and RT was observed in the Inuit patients referred to TOHCC. Lung cancer was the most common cancer in referred Inuit men and women. The survival rates for Inuit lung cancer patients referred to TOHCC were comparable to those in the rest of Canada. Further research is required to understand reasons for non-referral of Canadian Inuit to TOHCC.