Weekly administration of paclitaxel: theoretical and clinical basis

The rationale for weekly administration of paclitaxel, which acts on microtubules to arrest mitosis, is that more frequent delivery of moderate doses may achieve greater efficacy than standard doses every 3 weeks, through more sustained exposure of dividing tumor cells to its cytotoxic effects. This dose-dense approach to treatment may inhibit tumor regrowth between cycles and limit the emergence of malignant cell populations resistant to chemotherapy. More frequent exposure to paclitaxel may also enhance its apoptotic and antiangiogenic effects. Paclitaxel activity is considered to be independent of p53 status, in contrast to anticancer drugs that produce lesions on DNA, which achieve a better response if p53 is functional. Weekly therapy also has advantages in terms of improving paclitaxel therapeutic index. Clinical studies show that weekly paclitaxel is effective and that toxicity is acceptable. The response rates of single-agent paclitaxel varied from 21 to 86% in breast cancer, from 20% to 65% in ovarian cancer and from 30% to 56% in non-small cell lung cancer.