C. S. McArdle

Systemic inflammatory response predicts survival following curative resection of colorectal cancer

Some studies have shown that the presence of a systemic inflammatory response, as evidenced by raised circulating concentrations of C‐reactive protein (CRP), predicted recurrence and overall survival in patients with colorectal cancer. The aim of this study was to examine the relationship between the inflammatory response and overall and cancer‐specific survival in patients undergoing potentially curative resection for colorectal cancer.

Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer

A score based on the combination of the systemic inflammatory response and albumin hazards ratio (HR) 1.70, 95% CI 1.23 – 2.35, P=0.001) was comparable in prognostic value to that based on stage and performance status (HR 1.48, 95% CI 1.12 – 1.95, P=0.006) in patients with inoperable non-small-cell lung cancer. The former is simple to measure and well standardised.

Impact of anastomotic leakage on long-term survival of patients undergoing curative resection for colorectal cancer

The impact of anastomotic leakage on immediate postoperative mortality in patients undergoing potentially curative resection for colorectal cancer is well recognized. Its impact on long‐term survival is less clear. The aim of the present study was to evaluate the relationship between anastomotic leakage and long‐term survival in patients undergoing potentially curative resection for colorectal cancer.

The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer.

The relationship between the magnitude of systemic inflammatory response and the nutritional/functional parameters in patients with inoperable non-small cell lung cancer were studied. The extent of weight loss, albumin, C-reactive protein, performance status and quality of life was measured in 106 patients with inoperable non-small cell lung cancer (stages III and IV). Survival analysis was performed using the Cox proportional hazard model. The majority of patients were male and almost 80% had elevated circulating C-reactive protein concentrations (>10 mg l−1). On multivariate analysis, age (P=0.012), tumour type (0.002), weight loss (P=0.056), C-reactive protein (P=0.047), Karnofsky performance status (P=0.002) and fatigue (P=0.046) were independent predictors of survival. The patients were grouped according to the magnitude of the C-reactive protein concentrations (⩽10, 11–100 and >100 mg l−1). An increase in the magnitude of the systemic inflammatory response was associated with increased weight loss (P=0.004), reduced albumin concentrations (P=0.001), reduced performance status (P=0.060), increased fatigue (P=0.011) and reduced survival (HR 1.936 95%CI 1.414–2.650, P<0.001). These results indicate that the majority of patients with inoperable non-small cell lung cancer have evidence of a systemic inflammatory response. Furthermore, an increase in the magnitude of the systemic inflammatory response resulted in greater weight loss, poorer performance status, more fatigue and poorer survival.

Comparison of an inflammation-based prognostic score (GPS) with performance status (ECOG) in patients receiving platinum-based chemotherapy for inoperable non-small-cell lung cancer

The value of an inflammation-based prognostic score (GPS) was compared with performance status (ECOG) in patients (n=109) receiving platinum-based chemotherapy for inoperable non-small-cell lung cancer. On multivariate analysis with ECOG, white cell count and the GPS entered as covariates, only the GPS was a significant independent predictor of survival (HR 1.88, 95% CI 1.25–2.84, P=0.002).

Intrahepatic arterial versus intravenous fluorouracil and folinic acid for colorectal cancer liver metastases: a multicentre randomised trial.

BACKGROUND The liver is the most frequent site for metastases of colorectal cancer, which is the second largest contributor to cancer deaths in Europe. We did a randomised trial to compare an intrahepatic arterial (IHA) fluorouracil and folinic acid regimen with the standard intravenous de Gramont fluorouracil and folinic acid regimen for patients with adenocarcinoma of the colon or rectum, with metastases confined to the liver. METHODS We randomly allocated 290 patients from 16 centres to receive either intravenous chemotherapy (folinic acid 200 mg/m2, fluorouracil bolus 400 mg2 and 22-h infusion 600 mg/m2, day 1 and 2, repeated every 14 days), or IHA chemotherapy designed to be equitoxic (folinic acid 200 mg/m2, fluorouracil 400 mg/m2 over 15 mins and 22-h infusion 1600 mg/m2, day 1 and 2, repeated every 14 days). The primary endpoint was overall survival, and analysis was by intention to treat. FINDINGS 50 (37%) patients allocated to IHA did not start their treatment, and another 39 (29%) had to stop before receiving six cycles of treatment because of catheter failure. The IHA group received a median of two cycles (0-6), compared with 8.5 (6-12) for the intravenous group. 45 (51%) IHA patients who did not start or did not receive six cycles switched to intravenous treatment. In both groups, grade 3 or 4 toxicity was uncommon. Median overall survival was 14.7 months for the IHA group and 14.8 months for the intravenous group (hazard ratio 1.04 [95% CI 0.80-1.33], log-rank test p=0.79). Similarly, there was no significant difference in progression-free survival. INTERPRETATION Our results showed no evidence of an advantage in progression-free survival or overall survival for the IHA group; thus continued use of this regimen cannot be recommended outside of a clinical trial.

The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer

There is increasing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of common solid tumours. The aim of the present study was to examine the relationship between tumour T-lymphocyte subset infiltration, the systemic inflammatory response and cancer-specific survival in patients with colorectal cancer. In all, 147 patients undergoing potentially curative resection for colorectal cancer were studied. Circulating concentrations of C-reactive protein were measured prior to surgery. CD4+ and CD8+ T-lymphocyte infiltration of the tumour was assessed using immunohistochemistry and a point counting technique. When patients were grouped according to the percentage tumour volume of CD4+ T-lymphocytes, there was no difference in terms of age, sex, tumour site, stage and tumour characteristics. However, there was an inverse relationship between percentage tumour CD4+ T-lymphocytes and C-reactive protein (P<0.01). On univariate analysis, both C-reactive protein concentrations (P<0.001) and percentage tumour volume of CD4+ (P<0.05) T-lymphocytes were associated with cancer-specific survival. The results of the present study show that low tumour CD4+ T-lymphocyte infiltration is associated with elevated C-reactive protein concentrations and both predict poor cancer-specific survival.

Comparison of intermittent and continuous palliative chemotherapy for advanced colorectal cancer: a multicentre randomised trial

BACKGROUND Policies of UK clinicians regarding the duration of chemotherapy for patients with advanced colorectal cancer are not consistent. We aimed to compare effectiveness of continuous and intermittent chemotherapy in such patients. METHODS Patients who responded or had stable disease after receiving 12 weeks of the regimens described by de Gramont and Lokich, or raltitrexed chemotherapy, were randomised to either intermittent (a break in chemotherapy, re-starting on the same drug on progression), or continuous chemotherapy until progression. FINDINGS 354 patients (178 intermittent, 176 continuous) were enrolled from 42 UK centres. At randomisation, 41% of participants had part or complete response; 59% were stable. Only 66 (37%) patients allocated to intermittent treatment restarted as planned, after a median of 130 days. Median time on treatment after restarting was 84 days. Patients in the continuous group remained on treatment for a median of a further 92 days. Similar proportions of patients in both groups received second-line therapy. Patients on intermittent chemotherapy had significantly fewer toxic effects and serious adverse events than those in the continuous group. There was no clear evidence of a difference in overall survival (hazard ratio 0.87 favouring intermittent, 95% CI 0.69-1.09, p=0.23). INTERPRETATION Our findings provided no clear evidence of a benefit in continuing therapy indefinitely until disease progression. They showed that it is safe to stop chemotherapy after 12 weeks and re-start the same treatment on progression in patients with chemosensitive advanced colorectal cancer.

A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss.

SummaryThe use of megestrol acetate in the treatment of weight loss in gastrointestinal cancer patients has been disappointing. The aim of the present study was to compare the combination of megestrol acetate and placebo with megestrol acetate and ibuprofen in the treatment of weight loss in such patients. At baseline, 4–6 weeks and 12 weeks, patients underwent measurements of anthropometry, concentrations of albumin and C-reactive protein and assessment of appetite, performance status and quality of life using EuroQol-EQ-5D and EORTC QLQ-C30. Thirty-eight and 35 patients (median weight loss 18%) were randomized to megestrol acetate/placebo or megestrol acetate/ibuprofen, respectively, for 12 weeks. Forty-six (63%) of patients failed to complete the 12-week assessment. Of those evaluable at 12 weeks, there was a decrease in weight (median 2.8 kg) in the megestrol acetate/placebo group compared with an increase (median 2.3 kg) in the megestrol acetate/ibuprofen group (P < 0.001). There was also an improvement in the EuroQol-EQ-5D quality of life scores of the latter group (P < 0.05). The combination of megestrol acetate/ibuprofen appeared to reverse weight loss and appeared to improve quality of life in patients with advanced gastrointestinal cancer. Further trials of this novel regimen in weight-losing patients with hormone-insensitive cancers are warranted.

The relationship between weight loss and interleukin 6 in non-small-cell lung cancer

Markers of the inflammatory response, interleukin 6, C-reactive protein, albumin and full blood count, were measured in non-small-cell lung cancer (NSCLC) patients (n = 21) with and without weight loss ( > 5%). There were significant increases in circulating C-reactive protein (P < 0.001), interleukin 6 (P < 0.01) and platelets (P < 0.01) in the weight-losing group. Moreover, there was a statistically significant correlation (r = 0.785, P < 0.001) between interleukin 6 and C-reactive protein concentrations. These results are consistent with interleukin 6 and the acute phase response promoting weight loss in NSCLC.