Taxanes in paediatric oncology: and now?
Taxanes are a group of anticancer agents that target microtubules, promote their assembly, and stabilize them. The resulting effects are mitotic blockage and induction of apoptosis, whose mechanism of initiation remains to be fully determined. Among adults, taxanes are one of the most powerful and most commonly used anticancer drugs. They show a wide range of activity in malignancies such as breast, ovarian, and lung cancers. In paediatric oncology, pre-clinical and clinical data are quite limited. Six phase I studies, two phase II, and rare case reports have been published. This review will focus on the paediatric pre-clinical and clinical findings with taxanes. Based on data from the literature, we will try to explain the results and foresee the possible use of taxanes in paediatric oncology. Indeed, three main advances have been made regarding taxanes: (1) Increased efficacy when used in multidrug-based chemotherapy regimen. (2) New administration schedules based on anti-angiogenic properties when given at daily very low doses. (3) Development of new taxanes with decreased recognition by Pgp, the product of the MDR1 gene. Thus, although the initial experience with taxanes in paediatric oncology has been disappointing, it may be too early to leave out taxanes and we should further investigate their use among children with cancer.
Department of Paediatric Oncology, EA3286, UFR of Medicine and La Timone Children Hospital, Bd. Jean Moulin, 13885 Marseille, Cedex 5, France. nicolasandre@ap-hm.fr
Nicolas
N
André
Christophe
C
Meille
D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D002648:Child; D002986:Clinical Trials as Topic; D000077143:Docetaxel; D006801:Humans; D008495:Medical Oncology / Q000639:trends; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D010372:Pediatrics; D043823:Taxoids / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel