Assessing the impact of chemotherapy on tumor-related symptoms in advanced colorectal cancer.

In all patients with advanced colorectal cancer, disease eventually progresses following fluorouracil (5-FU) therapy, with a worsening of disease-related symptoms and quality of life (QOL). Irinotecan (CPT-11 [Camptosar]) has produced response rates of 16% to 27% in patients with 5-FU-refractory colorectal cancer, along with a modest survival gain and possible palliative benefit. Disease-related symptoms and QOL are major end points of palliation, although few studies have assessed them as primary end points of response. The concept of palliative response benefit has been applied successfully to randomized trials of systemic therapy in prostate and pancreatic cancers. This article will describe how this concept has been used in the design of a current phase II trial assessing the palliative benefit of irinotecan in patients with 5-FU-refractory colorectal cancer. This trial uses disease-related symptoms and performance status as primary end points. Palliative response was defined prospectively as one or more of the following; (1) 50% decrease in pain score; (2) 50% decrease in narcotic analgesic usage; or (3) 10-point increase in Karnofsky performance scale from baseline for 4 weeks, without deterioration of any of these parameters. The difficulties in using patient-oriented end points as response criteria in this trial and in the clinic will be addressed.