Combination of local temozolomide with local BCNU

• US 8,895,597 B2
• Filed: 06/17/2011
• Issued: 11/25/2014
• Est. Priority Date: 06/17/2010
• Status: Active Grant

• Current Assignee: Accelerating Combination Therapies, LLC
• Original Assignee: Betty Tyler, Henry Brem, Sarah Brem Sunshine, Violette Renard Recinos
• Inventors: Recinos, Violette Renard, Tyler, Betty, Sunshine, Sarah Brem, Brem, Henry
• Primary Examiner(s): Gembeh, Shirley V
• Application Number:
  US13/163,223
• Publication Number:
  US 20110313010A1
• Time in Patent Office: 1,257 Days
• Field of Search: 514/393, 514/589
• US Class Current: 514/393
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/175 having the group , >N—C(O)—N=N— or , e.g. carbonohydrazides, carbazones, semicarbazides, semicarbazones; Thioanalogues thereof
• CPC Class Codes: A61K 31/4188 condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The additive effect of combined intracranial carmustine (“BCNU”) with intracranial temozolomide (“TMZ”), and particularly in combination with radiation (“XRT”), in the treatment of two rat intracranial glioma models, the 9L gliosarcoma and the F98 glioma, demonstrates that local delivery of both drugs, especially in combination with radiation, is far more effective than delivery of either drug alone or one systemically and one locally, either with or without radiation. The triple therapy showed a significant improvement in survival when compared to controls (p=0.0004), local BCNU (p=0.0043), oral TMZ (p=0.0026), local TMZ (p=0.0105), and the combinations of either BCNU and XRT (p=0.0378) or oral TMZ and local BCNU (p=0.0154).

Claims

1. A composition for treating an individual with a solid tumor comprising a combination of carmustine and temozolomide

in a pharmaceutically acceptable polymeric carrier for sustained local administration of an effective amount of the carmustine and temozolomide to reduce tumor size or prolong survival of the individual with greater efficacy or reduced systemic side effects as compared to administration of either carmustine or temozolomide systemically.

2. The composition of claim 1 wherein the carrier is a polymeric wafer, disk, microparticle, or a microchip.

3. The composition of claim 1 wherein the carrier is a polymer comprising carmustine in a concentration range of 3.8-28% by weight.

4. The composition of claim 1 wherein the carrier is a polymer comprising temozolomide in a concentration range of 40-70% by weight.

5. The composition of claim 1 wherein the carrier is a polymer comprising 3.8% carmustine and 50% temozolomide.

6. A method of treating an individual with a tumor comprising administering the composition of claim 1.

7. The method of claim 6 wherein the individual has a brain tumor.

8. The method of claim 6 further comprising administering radiation to the individual.