Paclitaxel and docetaxel are active against a range of human cancers. Their antitumor activity is based on stabilization of the microtubule dynamics and thereby disruption of the cell cycle. The taxanes are administered as intravenous solutions in a short administration schedule. Distribution of both taxanes is rapid, with large volumes of distribution and significant binding to plasma proteins. The metabolism of paclitaxel is mediated primarily by the P450 cytochrome enzymes CYP2C8 and CYP3A, whereas docetaxel is only metabolized by CYP3A4. The most common toxicities after intravenous administration are neutropenia, hypersensitivity reactions, neurotoxicity, and alopecia. Several new administration forms are in development; albumin-bound paclitaxel (Abraxane) has recently been registered. Oral formulations of taxanes have been developed, and several are now undergoing phase I trials. New formulations might improve efficacy and safety and could be easier to use.
Purpose: Active specific immunotherapy (ASI) consisting of an autologous tumor cell vaccine given as adjuvant treatment has been shown to improve recurrence-free survival of patients with colon cancer. The aim of the current retrospective study was to investigate whether the beneficial effects of ASI given as adjuvant treatment correlated with microsatellite instability (MSI), which is considered an important biologic determinant of colon cancer.Experimental Design: Microsatellite status was assessed on archival tumor material from patients with stage II and III colon cancer. Microsatellite status was next associated with clinical outcome in control and ASI treatment groups using Kaplan-Meier analysis.Results : Conclusion: This retrospective study indicated that patients with MSI tumors did well, irrespective of treatment arm and tumor stage. The data also indicate that the clinical benefit, measured as recurrence-free survival, from adjuvant ASI treatment of patients with colon cancer was restricted to patients with MSS Dukes B tumors.
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