Toxicological testing of cytotoxic drugs (Review)

Cytotoxic drugs are a unique therapeutic class of fundamental importance in current antineoplastic chemotherapy. These drugs belong to many chemical a nd chemotherapeutic classes. They are cytotoxic by design and are able to c ause. serious dose-limiting adverse effects at therapeutic doses. Most anti neoplastic dosing strategies focus on minimizing, cytotoxicity rather than optimizing efficacy. In turn, cytotoxicity is interconnected with other the rapeutic considerations, including cell status (renewing vs. non-renewing c ell types), cell membrane transport integrity, intracellular activation sta tus, immune system integrity, cellular repair status, and drug resistance. Regulatory requirements for the development of cytotoxic drugs are not well characterized, and differences exist in regional requirements. A safety as sessment package which is utilized and accepted worldwide does not yet exis t, despite many efforts of harmonization. In this report, the authors intro duce a comprehensive safety assessment package for cytotoxic drugs, based o n institutional experience acquired globally with this class of drugs, that fulfills both scientific and world-wide regulatory requirements for this v ery important therapeutic category.