Сатраплатин

Использование

Antineoplastic.

Определение

ChEBI: A platinum coordination entity that consists of a central platunum atom bound to chloro (x2), acetate (x2), amino, and cyclohexylamino groups. Used for treatment of advanced prostate cancer.

Фармацевтические приложения

Satraplatin (JM216, cis,trans,cis-[PtCl2(OAc)2(NH3)(C6H5NH2)]) is a Pt(IV) or Pt4+ complex, which is active by oral administration, as it is more hydrophobic than cisplatin. This form of administration is very attractive because of the convenience and freedom it provides to the patient. Satraplatin also has a milder toxicity profile and is shows no cross-resistance with cisplatin. Satraplatin in combination with prednisone has completed phase III clinical trials against hormone-refractory prostate cancer. The results were very encouraging, but the overall survival rate did not improve significantly enough. As a result, the fast-track approval of the FDA was not granted.
Structurally, satraplatin consists of a Pt(IV) centre, which is coordinated by six ligands forming a close to octahedral geometry. In general, octahedral Pt(IV) complexes (low-spin d6) are much more kinetically inert than square planar Pt(II) complexes.

Клиническое использование

This newest organometallic agent currently is in clinical trials as a second-line agent for the treatment of hormone-refractory prostate cancer . There is hope that it also will find value in ovarian cancer and small cell lung cancer.

Побочные эффекты

As with other organoplatinum complexes, the diaquo form is active. At this early stage, the toxicity profile appears to be mild, with dose-related myelosuppression, particularly neutropenia and thrombocytopenia, being the major use-limiting side effect.

Метаболизм

Unlike the square-planar Pt(II) complexes currently on the market, it is active by the oral route. It is metabolized quickly in whole blood, producing up to six metabolites. The major metabolite is the desacetoxy analogue.