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4), and when used in combination with thalidomide [162] or docetaxel [58], they have yielded very encouraging results. PEGylation of xanthine oxidase (PEG-XO) [163] reduced the affinity of the native protein for all endothelium while inducing tumour accumulation of the protein by the EPR effect, leading to significant suppression of tumour growth following administration of hypoxanthine (described in detail in Sect. 1). 1 Use of targeting moieties to deliver drugs to the tumour vasculature An alternative approach for targeting the tumour vasculature with a polymer therapeutic consists of functionalizing the cytotoxic drug-polymer conjugate with a targeting moiety that specifically recognizes the tumour endothelial cell.

In 2003, the FDA approval was extended to include initial surgery for malignant glioma based on two additional randomized prospective studies that demonstrated improved survival and safety [145]. Studies have also reported benefits for experimental brain metastases [146] and invasive pitu- Polymer Therapeutics for Cancer: Current Status and Future Challenges 39 itary adenomas [147]. Local delivery of chemotherapeutics from longlasting implantable lipid formulations to spinal fluid has also been used clinically to treat carcinomatous meningitis [148].

Moses MA, Brem H, Langer R (2003) Cancer Cell 4:337 5. Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Lino Cutajar C, Zurlo A, Pierart M (2002) Lancet 360:103 6. Tsukagoshi S (2002) Gan To Kagaku Ryoho 29:1675 7. Heyns CF, Simonin MP, Grosgurin P, Schall R, Porchet HC (2003) BJU Int 92:226 8. Langer R (1998) Nature 392:5 9. Brem H, Ewend MG, Piantadosi S, Greenhoot J, Burger PC, Sisti M (1995) J Neurooncol 26:111 Polymer Therapeutics for Cancer: Current Status and Future Challenges 57 10.

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