Local chemotherapy of F98 rat glioblastoma with paclitaxel and carboplatin embedded in liquid crystalline cubic phases
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Implanted drug carrier systems for retarded chemotherapy against gliomas are mainly based upon polymers containing nitrosoureas. The authors have developed an intracavitary carrier system of biodegradable liquid crystalline cubic phases encapsulating carboplatin and paclitaxel and studied it for release kinetics, antitumor activity, and survival prolongation. A total of 61 Fisher rats with F98 tumors were divided into six treatment groups at day 12 post-inoculation, receiving either no treatment, surgery with partial tumor resection, or partial resection with implantation of cubic phases containing either paclitaxel and carboplatin, paclitaxel alone, carboplatin alone, or no drug. Animals were killed for tumor size analysis at day 21 post-inoculation (n=28) or were included in survival studies (n=33). Additional 12 animals received a paclitaxel/carboplatin application and were killed at different time intervals (6 h, 24 h, 48 h, 5 d, 7 d, 10 d post-agent application) for in vivo diffusion studies. Animals from the paclitaxel/carboplatin group showed a significantly smaller tumor (mean 3.25 mm2 ± SD 1.79 mm2) than animals from the control group (15.30 ± 5.86 mm2; P=0.0031), animals having received the empty matrix (11.62 ± 6.66 mm2; P=0.0241), and animals after tumor resection without implantation (20.87 ± 3.56 mm2; P ≤ 0.0001). There was no significant difference in survival. Carboplatin was found in brain tissue at 6 h, paclitaxel was found at up to 48 h after implantation at 3 mm distance. Biodegradable crystalline cubic phases embedding cytotoxic drugs as paclitaxel and carboplatin might play an important role in local glioblastoma treatment.
Keywordscarboplatin CuboSphere™ F98 rat glioma glioblastoma intracavitary chemotherapy liquid crystalline cubic phases paclitaxel
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- 2.Brem, H, Piantadosi, S, Burger, PC, Walker, M, Selker, R, Vick, NA, Black, K, Sisti, M, Brem, S, Mohr, G, et al. 1995Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomasThe Polymer Brain Tumor Treatment Group. Lancet34510081012Google Scholar
- 4.Ericsson, B, Eriksson, PO 1991Cubic phases as delivery systems for peptide drugsPolym Drugs Drug Deliv Syst469251265Google Scholar
- 5.Wyatt, DM, Dorschel, D 1992Cubic phase delivery system composed of glyceryl monooleate and water for sustained release of water soluble drugsPharm Tech16116130Google Scholar
- 7.Tardieu, A, Luzzati, V 1970Polymorphism of lipidsA novel cubic phase-a cage-like network of rods with enclosed spherical micelles. Biochem Biophys Acta2191117Google Scholar
- 8.Larsson, K, Fontell, K, Krog, N 1980Structural relationship between lamellar, cubic and hexagonal phases in monoglyeride–water systemsPossibility of cubic structures in biological systems. Chem Phys Lipids27321328Google Scholar
- 10.Engstrom, S 1990Cubic phases as drug delivery systemsPolym Prep (Am Chem Soc, Div Polym Che)31157158Google Scholar
- 17.Chang, SM, Kuhn, JG, Robins, HI, Schold, SC,Jr, Spence, AM, Berger, MS, Mehta, M, Pollack, IF, Rankin, C, Prados, MD 2001A phase II study of paclitaxel in patients with recurrent malignant glioma using different doses depending upon the concomitant use of anticonvulsants: a North American Brain Tumor Consortium reportCancer91417422CrossRefPubMedGoogle Scholar
- 21.Gaver, RC, Deeb, G 1986High-performance liquid chromatographic procedures for the analysis of carboplatin in human plasma and urineCanc Chemother Pharmacol16201206Google Scholar
- 23.Muggia, FM, Braly, PS, Brady, MF, Sutton, G, Niemann, TH, Lentz, SL, Alvarez, RD, Kucera, PR, Small, JM 2000Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a gynecologic oncology study groupJ Clin Oncol18106115PubMedGoogle Scholar
- 24.Gatzemeier, U, Pawel, J, Gottfried, M, ten Velde, GP, Mattson, K, DeMarinis, F, Harper, P, Salvati, F, Robinet, G, Lucenti, A, Bogaerts, J, Gallant, G 2000Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancerJ Clin Oncol1833903399PubMedGoogle Scholar