TailorDose-CPA

Everybody deserves to be treated differently

TailorDose® CPA 

A novel and unique tool to measure and adjust cyclophosphamid dose during treatment of breast cancer.

Background

Worldwide, breast cancer comprises 10 % of all cancer incidences among women, making it the most common type of non-skin cancer in women and the fifth most common cause of cancer death. In Sweden 7000 females are diagnosed by this disease and although the treatments constantly have been improved, around 1500 die annually. For the majority of these women chemotherapy is used, often in combination with surgery, radiation therapy and hormone therapy.

Of the globally 1.2 milj. females being diagnosed for this disease, approx. 600 000 are treated with cyclophosphamide. Chemotherapeutic treatments always include the nor-nitrogen mustard agent cyclophosphamide (CPA) combined with a couple of other cytotoxic agents which varies (so called multi chemotherapy). Doses are given according to standard protocols (calc. from the patients body surface area; BSA dose). These protocols do not consider well known inter-individual variability regarding metabolism and rate of clearance of used cytostatic drugs. Furthermore, CPA is a ”prodrug”; it is hydroxylated in the liver to an unstable hydroxylated precursor (4HO-CPA) which is transported by diffusion through membranes, e.g. into the nucleus, were it falls apart and form phosphoramide mustard (PAM) possessing the cytotoxic effect. This metabolite, PAM, is known to vary with several hundred percent between individuals (e.g. Xie H et al, Eur J Pharm Sci. 1, 2006:54-61). However, this individual variation, meaning 30 % of the patients being dosed too high or too low, can not be identified as no clinical applicable methods to measure the in vivo dose of PAM exists.

TailorDose® and breast cancer

The introduction of the TailorDose® provides the oncologist an exact measurement of how the individual responded to administered dose of CPA. The concentration of the cytotoxic active metabolite, PAM, can be determined through the FIRE method and expressed as area under the blood concentration vs. time curve (AUC dose). This is a direct measurement as specific biomarkers  are formed in direct relation to the individual dose. This means that the oncologist will get a tool to obtain accurate data for individual dose adjustment. For the patient this means higher safety and reduced risk for severe side effects such as immunodepression (CPA is immunotoxic), or ineffective therapy (too low cytotoxicity). Dose adjustments by TailorDose®. The first evaluation of this new approach involving 150 patients receiving cyclophosphamide indicate that 22 % of the subjects are given a dose that is too low (affecting the efficacy of the treatment) and 17 % are given a dose which is too high (leading to higher risk of severe adverse side effects, often expressed late in the therapy).

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