Abstract
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.
Similar content being viewed by others
References
JC Kiwit FW Floeth WJ Bock (1996) ArticleTitleSurvival in malignant glioma: analysis of prognostic factors with special regard to cytoreductive therapy Zentralbl Neurochir 57 76–88 Occurrence Handle1:STN:280:BymB2s3htlY%3D Occurrence Handle8779273
H Brem S Piantadosi PC Burger M Walker R Selker NA Vick K Black M Sisti S Brem G Mohr et al. (1995) ArticleTitlePlacebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas The Polymer Brain Tumor Treatment Group. Lancet 345 1008–1012 Occurrence Handle1:STN:280:ByqB2c%2FisVU%3D
FK Albert M Forsting K Sartor HP Adams S Kunze (1994) ArticleTitleEarly postoperative magnetic resonance imaging after resection of malignant glioma: objective evaluation of residual tumor and its influence on regrowth and prognosis Neurosurgery 34 45–60 Occurrence Handle1:STN:280:ByuC28npslQ%3D Occurrence Handle8121569
B Ericsson PO Eriksson (1991) ArticleTitleCubic phases as delivery systems for peptide drugs Polym Drugs Drug Deliv Syst 469 251–265 Occurrence Handle1:CAS:528:DyaK3MXls1Kms7k%3D
DM Wyatt D Dorschel (1992) ArticleTitleCubic phase delivery system composed of glyceryl monooleate and water for sustained release of water soluble drugs Pharm Tech 16 116–130 Occurrence Handle1:CAS:528:DyaK3sXksFGqtQ%3D%3D
A Pampel D Michel R Reszka (2002) ArticleTitlePulsed field gradient MAS-NMR studies of the mobility of carboplatin in cubic liquid-crystalline phases Chem Phys Lett 357 131–136 Occurrence Handle10.1016/S0009-2614(02)00468-2 Occurrence Handle1:CAS:528:DC%2BD38Xjtlyqu7c%3D
A Tardieu V Luzzati (1970) ArticleTitlePolymorphism of lipids A novel cubic phase-a cage-like network of rods with enclosed spherical micelles. Biochem Biophys Acta 219 11–17 Occurrence Handle1:CAS:528:DyaE3MXjsFU%3D
K Larsson K Fontell N Krog (1980) ArticleTitleStructural relationship between lamellar, cubic and hexagonal phases in monoglyeride–water systems Possibility of cubic structures in biological systems. Chem Phys Lipids 27 321–328 Occurrence Handle1:CAS:528:DyaL3MXhtler
PO Eriksson G Lindblom (1993) ArticleTitleLipid and water diffusion in biocontinuous cubic phases measured by NMR Biophys J 64 129–136 Occurrence Handle1:CAS:528:DyaK3sXhs1elsb8%3D Occurrence Handle8431537
S Engstrom (1990) ArticleTitleCubic phases as drug delivery systems Polym Prep (Am Chem Soc, Div Polym Che) 31 157–158
JC Shah Y Sadhale DM Chilukuri (2001) ArticleTitleCubic phase gels as drug delivery systems Adv Drug Deliv Rev 47 229–250 Occurrence Handle1:CAS:528:DC%2BD3MXislGls7c%3D Occurrence Handle11311994
AI Qureshi MF Suri J Khan M Sharma K Olson LP Guterman LN Hopkins (2001) ArticleTitleSuperselective intra-arterial carboplatin for treatment of intracranial neoplasma: experience in 100 procedures J Neurooncol 51 151–158 Occurrence Handle1:STN:280:DC%2BD3MzhtlGrtA%3D%3D Occurrence Handle11386412
A Olivi MG Ewend T Utsuki B Tyler AJ Domb DJ Brat H Brem (1996) ArticleTitleInterstitial delivery of carboplatin via biodegradable polymers is effective against experimental glioma in rat Cancer Chemother Pharmacol 39 90–96 Occurrence Handle1:CAS:528:DyaK2sXis1ajsrw%3D Occurrence Handle8995504
CA Hurwitz LC Strauss J Kepner C Kretschmar MB Harris H Friedman L Kun R Kadota (2001) ArticleTitlePaclitaxel for the treatment of progressive or recurrent childhood brain tumors: a pediatric oncology phase II study J Pediatr Hematol Oncol 23 277–281 Occurrence Handle1:STN:280:DC%2BD3Mvhs1Gruw%3D%3D Occurrence Handle11464982
MC Chamberlain P Kormanik (1999) ArticleTitleSalvage chemotherapy with taxol for recurrent anaplastic astrocytoma J Neurooncol 43 269–276 Occurrence Handle1:STN:280:DC%2BD3c%2FisV2mtQ%3D%3D Occurrence Handle10563433
MD Prados SC Schold AM Spence MS Berger LD McAllister MP Mehta MR Gilbert D Fulton J Kuhn K Lamborn DJ Rector SM Chang (1996) ArticleTitlePhase II study of paclitaxel in patients with recurrent malignant glioma J Clin Oncol 14 2316–2321 Occurrence Handle1:CAS:528:DyaK28XltFSqsbk%3D Occurrence Handle8708723
SM Chang JG Kuhn HI Robins SC Schold SuffixJr AM Spence MS Berger M Mehta IF Pollack C Rankin MD Prados (2001) ArticleTitleA 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 report Cancer 91 417–422 Occurrence Handle10.1002/1097-0142(20010115)91:2<417::AID-CNCR1016>3.0.CO;2-9 Occurrence Handle1:CAS:528:DC%2BD3MXhtVekur4%3D Occurrence Handle11180089
CM Spencer D Faulds (1994) ArticleTitlePaclitaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potentials in the treatment of cancer Drugs 48 794–847 Occurrence Handle1:STN:280:ByqC3snovVw%3D Occurrence Handle7530632
KA Walter MA Cahan A Gur B Tyler J Hilton OM Colvin PC Burger A Domb H Brem (1994) ArticleTitleInterstitial taxol delivered from a biodegradable polymer implant against experimental malignant glioma Cancer Res 54 2207–2212 Occurrence Handle1:CAS:528:DyaK2cXivVSjurY%3D Occurrence Handle7909720
L Ko A Koestner W Wechsler (1980) ArticleTitleMorphological characterization of nitrosourea-induced glioma cell lines and clones Acta Neuropathol 51 23–31 Occurrence Handle1:STN:280:Bi6D2MfpslU%3D Occurrence Handle7435138
RC Gaver G Deeb (1986) ArticleTitleHigh-performance liquid chromatographic procedures for the analysis of carboplatin in human plasma and urine Canc Chemother Pharmacol 16 201–206 Occurrence Handle1:CAS:528:DyaL28XktlGjsrw%3D
SM Longnecker RC Donehower AE Cates TL Chen RB Brundrett LB Grochow DS Ettinger M Colvin (1987) ArticleTitleHigh-performance liquid chromatographic assay for taxol in human plasma and urine and pharmocokinetics in a phase I trial Cancer Treat Rep 71 53–59 Occurrence Handle1:CAS:528:DyaL2sXktlehtw%3D%3D Occurrence Handle2878719
FM Muggia PS Braly MF Brady G Sutton TH Niemann SL Lentz RD Alvarez PR Kucera JM Small (2000) ArticleTitlePhase 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 group J Clin Oncol 18 106–115 Occurrence Handle1:CAS:528:DC%2BD3cXmtFSrtQ%3D%3D Occurrence Handle10623700
U Gatzemeier J Pawel Particlevon M Gottfried GP ten Velde K Mattson F DeMarinis P Harper F Salvati G Robinet A Lucenti J Bogaerts G Gallant (2000) ArticleTitlePhase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer J Clin Oncol 18 3390–3399 Occurrence Handle1:STN:280:DC%2BD3M%2FgvFWlsw%3D%3D Occurrence Handle11013280
RF Barth (1998) ArticleTitleRat brain tumor models in experimental neuro-oncology: the 9L, C6, T9, F98, RG2 (D74), RT-2 and CNS-1 gliomas J Neurooncol 36 91–102 Occurrence Handle10.1023/A:1005805203044 Occurrence Handle1:STN:280:DyaK1c7osVOntw%3D%3D Occurrence Handle9525831
RJ Tamargo JS Myseros JI Epstein MB Yang M Chasin H Brem (1993) ArticleTitleInterstitial chemotherapy for the 9L gliosarcoma: controlled release polymers for drug delivery in the brain Cancer Res 53 329–333 Occurrence Handle1:CAS:528:DyaK3sXhtlWqsr8%3D Occurrence Handle8417826
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Eckardstein, K.L.v., Patt, S., Kratzel, C. et al. Local chemotherapy of F98 rat glioblastoma with paclitaxel and carboplatin embedded in liquid crystalline cubic phases. J Neurooncol 72, 209–215 (2005). https://doi.org/10.1007/s11060-004-3010-6
Issue Date:
DOI: https://doi.org/10.1007/s11060-004-3010-6