• Top
• Oral presentation

Oral presentation

Systemic anti-tumor therapy with conventional cytotoxic agents used as a monotherapy or in combination protocols is only rarely tumor-cell selective. The difference between the effect on malignant and non-malignant cells is a quantitative one, not qualitative. Therefore, side-effects and toxicities of cytotoxic drugs usually reflect the impact on tumor cells. The magnitude of toxic effects on normal cells and tissues depends upon the nature of the drug and the dosage, as well as the time-course and schedule of the chemotherapy in which they are used. Besides that, patient-dependent factors (performance status, previously received chemotherapies) likewise impact the safety and toxicity. Major side-effects of conventional cytotoxic drugs include: myelosuppression, immunosuppression, major organ toxicity (pulmonary, hepatic, renal, gastrointestinal), neurotoxicity, gonadal toxicity and teratogenicity, alopecia, nausea and vomiting and induction of secondary neoplasias.

For all approved non-cytotoxic antineoplastic substances (biological response modifiers, BRM, Monoclonal Antibodies, MoAb) as well as for the majority of the currently investigated so-called small molecules (signal transduction inhibitors) the toxicity profile is substantially different. For BRM like Interferons and Interleukin-2, the major toxicity comprises a spectrum of side-effects best described with the term cytokine release syndrome (i.e. high fever, vasculary leakage, interstitial edemas, renal impairment, hypotension). MoAb (either unconjugated or linked to a cytotoxic or radiotoxic moiety) with specificity for a given antigen have a selective mode of anti-tumor action. The side-effects of MoAb, especially those of murine origin, are characterized by allergic reactions and the development of anti-antibodies. With the development of humanized and human MoAb, the safety substantially improved with currently only few mild allergic-type adverse reactions. The last group of anti-neoplastic drugs which are being developed within the last years, the signal-transduction inhibitors, show a broad spectrum of adverse events which are not yet fully understood. This includes e.g. skin, mild hematologic, gastrointestinal and hepatic toxicity and ocassionally nausea and vomiting. The nature and severity of these adverse events differs from drug to drug. Since (with the exception of the bcr-abl kinase inhibitor Gleevec®) signal transduction inhibitors have not yet received market application, the efficacy, safety and toxicity has to fully be determined within the next few years.

The clinical endpoints, the design of phase I-III studies and the pharmacological requirements of clinical studies which are necessary for the development of cytotoxic drugs, antibodies and signal-transduction inhibitors show substantial differences. Varying designs and approaches will be compared and discussed.

Have something to say? Post a comment on this article!