Increasing chemotherapy in small-cell lung cancer: from dose intensity and density to megadoses

The hypothesis that increasing cytotoxic dose intensity will improve cancer cure rates is compelling. Although supporting evidence for this hypothesis has accrued for several tumor types, including lymphomas, breast cancer, and testicular cancers, it remains unproven. Small-cell lung cancer is extremely chemo- and radiosensitive, with a response rate of 80% achieved routinely, but few patients are cured by chemoradiotherapy. In this setting, increased cytotoxic dose intensity might improve cure rates. The finding that response rates in small-cell lung cancer correlate with received cytotoxic dose intensity merely confirms that "less is worse" and "more is better." Within conventional ranges, dose intensity can be increased with the support of hematopoietic growth factors and/or by shortening treatments intervals; however, dose intensity could be increased by only 20%-30%, and a survival advantage has not been clearly demonstrated. Given its high chemosensitivity, small-cell lung cancer was one of the first malignancies deemed suitable for increasing dose intensity and even for the use of a megadose with the support of autologous bone marrow transplantation. Some interest is emerging again due to improvements in supportive care, such as the availability of hematopoietic growth factors and peripheral blood progenitor cells.