Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases

Christodoulou, C.; Bafaloukos, Dimitrios; Kosmidis, P.; Samantas, E.; Bamias, Aristotelis; Papakostas, Pavlos; Karabelis, A.; Bacoyiannis, C.; Skarlos, Dimosthenis

doi:10.1023/a:1008354323167

Cited by 159 publications

(60 citation statements)

References 27 publications

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“…Different investigators have tested temozolomide in pretreated and preirradiated patients and have obtained a median survival time of 4 to 7 months. 5,34 Similar results were produced in our series of 4 patients, with a median survival of 8.1 months. The best response obtained was 2 SD.…”

Section: Breast Metastasissupporting

confidence: 84%

Enhanced chemotherapy delivery by intraarterial infusion and blood‐brain barrier disruption in the treatment of cerebral metastasis

Fortin

Gendron

Boudrias

et al. 2007

Cancer

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Cationic polyurethane‐fluorinated acrylate hybrid dispersions (PUFA) were prepared by the copolymerization of styrene, butyl acrylate, and 2,2,3,4,4,4‐hexafluorobutyl methacrylate in the medium of crosslinked polyurethane via phase inversion polymerization. The said polyurethane was synthesized in acetone from 2,4‐tolyene diisocyanate, N‐methyldiethanolamine, trimethylolpropane, and soft polyester diol block. The influences of hydrophilic monomer on the surface properties, immersion behaviors, particle size and, zeta potential of the dispersions were investigated. The results show that the addition of hydrophilic monomer can be advantaged to the stability of dispersions and yet will increase the surface free energy by more than 19.9%. The PUFA coating films cured at ambient conditions have the lower surface free energy (less than 0.02033 J/m2). At the same time, there is an obvious mobility of fluorinated groups in fluorinated polymer films. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006

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Section: Breast Metastasissupporting

confidence: 84%

Enhanced chemotherapy delivery by intraarterial infusion and blood‐brain barrier disruption in the treatment of cerebral metastasis

Fortin

Gendron

Boudrias

et al. 2007

Cancer

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“…However, when TMZ was tested for activity against brain metastatic breast cancer in heavily pretreated patients, it revealed mixed outcomes that ranged from "encouraging activity" and "disease control" to "well-tolerated, but no objective responses" (4)(5)(6)(7)(8)(9). The underlying basis for these inconsistent results was not investigated, but it is conceivable that these differences may have been because of variable expression levels of O6-methylguanine-DNA methyltransferase (MGMT; also called O6-alkylguanine-DNA alkyltransferase, AGT), a DNA repair enzyme that removes alkyl groups located on the O6-position of guanine (10,11).…”

Section: Introductionmentioning

confidence: 99%

A Novel Temozolomide–Perillyl Alcohol Conjugate Exhibits Superior Activity against Breast Cancer Cells In Vitro and Intracranial Triple-Negative Tumor Growth In Vivo

Chen

Cho

Wang

et al. 2014

Molecular Cancer Therapeutics

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There is no effective therapy for breast cancer that has spread to the brain. A major roadblock is the bloodbrain barrier (BBB), which prevents the usual breast cancer drugs from effectively reaching intracranial metastases. The alkylating agent temozolomide (TMZ) is able to penetrate the BBB and has become the gold standard for chemotherapeutic treatment of glioblastoma. However, when it was tested in clinical trials for activity against brain metastases of breast cancer, the results were mixed and ranged from "encouraging activity" to "no objective responses." In an effort to generate an agent with greater activity against intracranial breast metastases, we synthesized a TMZ analog where the natural product perillyl alcohol (POH) was covalently linked to TMZ's amide functionality. The resulting novel compound, called TMZ-POH (T-P), displayed greatly increased anticancer activity in a variety of breast cancer cell lines, inclusive of TMZ-resistant ones. It caused DNA damage and cell death much more efficiently than its parental compound TMZ, because linkage with POH increased its biologic half-life and thus provided greater opportunity for placement of cytotoxic DNA lesions. In an intracranial mouse tumor model with triple-negative breast cancer, T-P revealed considerably greater therapeutic efficacy than TMZ, where a single cycle of treatment extended median survival benefit from 6 days (in the case of TMZ) to 28 days. At the same time, T-P seemed to be well tolerated by the animals. Thus, T-P may have potential as a novel therapy for brain-targeted breast cancer metastases.

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“…More recent studies suggest that chemotherapeutic agents that have better penetration of the BBB, such as TMZ, may have a role in newly diagnosed metastases, not just as salvage therapy (25,26). The agents that have shown promise include cyclophosphamide, 5-fluorouracil, methotrextate and vincristine combined, and TMZ, although the use of TMZ has been restricted to recurrent breast metastases (19,27,28). The use of TMZ in recurrent breast cancer brain metastases has shown modest increases in survival, although this patient population represents a selection of the most aggressive and refractory cancers that have withstood surgery, WBRT, and multiple other systemic chemotherapies.…”

mentioning

confidence: 99%

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Upadhyay

Tyler

Patta³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Brain metastases represent the most common intracranial tumors in adults. Adequate chemotherapy delivery to the CNS is hindered by the blood–brain barrier. Efforts in intracranial chemotherapy delivery aim to maximize CNS levels while minimizing systemic toxicity; however, the success has been limited thus far. In this work, intracranial implanted doxorubicin and temozolomide microcapsules are compared with systemic administration in a novel rodent model of breast adenocarcinoma brain metastases. These microcapsules are versatile and efficacious, but that efficacy may depend on the ability of the chemotherapy to diffuse in brain tissue. These insights apply to other non-CNS applications of local drug delivery, and drugs should be evaluated based on their ability to penetrate the targeted tissue as well as their inherent efficacy.

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Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases

Abstract: Temozolomide demonstrated encouraging activity in the treatment of brain metastases in heavily pretreated patients with solid tumors, and was safe and well tolerated.

Cited by 159 publications

References 27 publications

Enhanced chemotherapy delivery by intraarterial infusion and blood‐brain barrier disruption in the treatment of cerebral metastasis

Enhanced chemotherapy delivery by intraarterial infusion and blood‐brain barrier disruption in the treatment of cerebral metastasis

A Novel Temozolomide–Perillyl Alcohol Conjugate Exhibits Superior Activity against Breast Cancer Cells In Vitro and Intracranial Triple-Negative Tumor Growth In Vivo

Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

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