Clinically approved organic chemotherapeutic drugs such as cytarabine, dacarbazine and anastrozole were attached to B12via a {CN-trans-Pt(NH3)2}-bridge to yield [{Co}-CN-{trans-Pt(NH3)2}-{drug}](2+). The active organic drugs are protected by the platinum complex and by B12, which represents at the same time the targeting vector. We refer to these bioconjugates as two-step activation prodrugs since two reactions are finally required to liberate the actual organic drugs. All three prodrugs are soluble and stable in water. The physiological stability and the therapeutic efficiency of [{Co}-CN-{trans-Pt(NH3)2}-{cytarabine}](2+) (2) were studied. Under physiological conditions, 2 is stable for 3 days. Its affinity to the cobalamin transport proteins (haptocorrin, intrinsic factor and transcobalamin) is not substantially affected despite the introduction of a bulky group in the β-axial position. The cleavage of the [trans-CN-Pt(NH3)2-{cytarabine}](+) complex was observed upon chemical reduction of Co(III)→ Co(II) with Zn(0). Cytarabine was subsequently released from the cleaved complex to exhibit its cytotoxicity. 2 displayed a reduced cytotoxicity (IC50 = 230 ± 62 nM) as compared to cytarabine (IC50 = 30 ± 5 nM). However, cytarabine released from 2 showed comparable cytotoxicity (IC50 = 30 ± 11 nM).