Surgical resection is the primary treatment in patients with colorectal cancer, but more than one half of them eventually die from metastatic disease. The prognosis in metastatic colorectal cancer is poor, with a median survival of six to nine months from the time of detection of metastases. Chemotherapy aims to reduce symptoms, prolong survival and improve quality of life, but there is no universally accepted standard therapy or route of administration, and the duration of treatment varies widely. Palliative chemotherapy is now offered to an increasing proportion of patients with advanced colorectal cancer. The European Colorectal Cancer Collaborative Group analyzed data from multiple sources to determine the benefits and harms of palliative chemotherapy in patients with locally advanced or metastatic colorectal cancer and to compare the outcomes in elderly and younger patients.
Data were gathered by electronic searches of several databases of relevant trials, reference lists of review articles, recent conference abstracts and contact with authors of eligible studies. All relevant identified studies were assessed for quality by two reviewers. The primary outcomes included survival, disease progression, treatment toxicity, quality of life or relief of symptoms, and cost effectiveness.
Data were abstracted from 13 trials published between 1983 and 1998 that involved 1,365 patients. The authors confirmed that 10 trials were truly random, with adequate concealment. The allocation method was not described in the remaining three trials, and information from the investigators was unavailable. Individual patient data were obtained from seven of the 10 trials (866 of 1,365 patients [63 percent]). A meta-analysis of these trials revealed that palliative chemotherapy was associated with a 35 percent decrease in the risk of death—an absolute improvement in survival of 16 percent at six and 12 months, and an improvement in median survival of 3.7 months (8.0 months in the control group versus 11.7 months in the chemotherapy group). Three of the 13 trials (482 patients) provided individual patient data on tumor progression. The absolute difference in progression was 25 percent at six and 12 months. The median duration of progression-free survival was four months in the control group and 10 months in the chemotherapy group.
Of the 13 trials, 10 provided data on chemotherapy toxicity, and four graded toxicity according to a standarized, validated scale. Results from only one study provided reliable comparison data between the treatment and control arms, indicating that the treatment group experienced severe adverse events compared with the control group (79 versus 67 percent, respectively). Because of the variance in drugs and a lack of objective standardized data, a meaningful summary of treatment-related toxicities was not possible. The authors were unable to obtain sufficient comparable data on cost effectiveness or quality of life. Very few elderly patients (75 years or older) were included in the trials. Three age groups (younger than 50 years, 50 to 64 years of age and 65 years or older) were analyzed, and no relationship between age and effect of treatment on survival was evident.
The authors conclude that chemotherapy can effectively prolong survival in patients with advanced colorectal cancer, but the median survival rate is short. They call for further studies using standardized, validated instruments to examine toxicity, quality of life and symptom control during and after chemotherapy.