Applications of dose intensity to problems in chemotherapy of breast and colorectal cancer.

Studies were analyzed to show the correlation of response with dose intensity of single-agent 5-fluorouracil (5-FU) against colorectal cancer, multiagent CMF (cyclophosphamide, methotrexate, 5-FU) regimens against advanced breast cancer, and adjuvant therapy in stage II breast cancer. In colorectal cancer studies, subgroups in which 5-FU was given by intravenous (IV) bolus, infusion, and orally were analyzed. One study reported delivered dose levels after reductions for toxicity. This allowed calculations of received dose intensity for the three dose levels, and comparison with projected dose intensities. The data suggest that the dose-intensity response line is steep, once a threshold dose intensity has been surpassed. An increase of only 100 mg/m2/wk of received dose intensity of 5-FU increased the response rate from 20% to 29%, which in relative terms was an increase of almost 50%. Received dose intensity may correlate with response, not only in groups of patients, but also in individual patients, and this may, in fact, be the most important application of the concept of dose intensity.