Trans-sodium crocetinate enhancing survival and glioma response on magnetic resonance imaging to radiation and temozolomide.

Abstract

OBJECT:

Glioblastoma (GB) tumors typically exhibit regions of hypoxia. Hypoxic areas within the tumor can make tumor cells less sensitive to chemotherapy and radiation therapy. Trans-sodium crocetinate (TSC) has been shown to transiently increase oxygen to hypoxic brain tumors. The authors examined whether this improvement in intratumor oxygenation translates to a therapeutic advantage when delivering standard adjuvant treatment to GBs.

METHODS:

The authors used C6 glioma cells to create a hypoxic GB model. The C6 glioma cells were stereotactically injected into the rat brain to create a tumor. Fifteen days later, MR imaging was used to confirm the presence of a glioma. The animals were randomly assigned to 1 of 3 groups: 1) temozolomide alone (350 mg/m(2)/day for 5 days); 2) temozolomide and radiation therapy (8 Gy); or 3) TSC (100 microg/kg for 5 days), temozolomide, and radiation therapy. Animals were followed through survival studies, and tumor response was assessed on serial MR images obtained at 15-day intervals during a 2-month period.

RESULTS:

Mean survival (+/- SEM) of the temozolomide-alone and the temozolomide/radiotherapy groups was 23.2 +/- 0.9 and 29.4 +/- 4.4 days, respectively. Mean survival in the TSC/temozolomide/radiotherapy group was 39.8 +/- 6 days, a statistically significant improvement compared with either of the other groups (p < 0.05). Although tumor size was statistically equivalent in all groups at the time of treatment initiation, the addition of TSC to temozolomide and radiotherapy resulted in a statistically significant reduction in the MR imaging-documented mean tumor size at 30 days after tumor implantation. The mean tumor size in the TSC/temozolomide/radiotherapy group was 18.9 +/- 6.6 mm(2) compared with 42.1 +/- 2.7 mm(2) in the temozolomide-alone group (p = 0.047) and 35.8 +/- 5.1 mm(2) in the temozolomide/radiation group (p = 0.004).

CONCLUSIONS:

In a hypoxic GB model, TSC improves the radiological and clinical effectiveness of temozolomide and radiation therapy. Further investigation of this oxygen diffusion enhancer as a radiosensitizer for hypoxic brain tumors seems warranted.

• Authors: Jason Sheehan, Christopher P Cifarelli, Kasandra Dassoulas, Claire Olson, Jessica Rainey, Shaojie Han
• Journal: Journal of neurosurgery (J Neurosurg) Vol. 113 Issue 2 Pg. 234-9 (Aug 2010) ISSN: 1933-0693 [Electronic] United States
• PMID: 20001586 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Radiation-Sensitizing Agents
• trans-sodium crocetinate
• Vitamin A
• Carotenoids
• Dacarbazine
• Oxygen
• Temozolomide

Topics

• Animals
• Antineoplastic Agents, Alkylating (pharmacology)
• Brain Neoplasms (drug therapy, pathology, radiotherapy)
• Carotenoids
• Cell Line, Tumor
• Combined Modality Therapy
• Dacarbazine (analogs & derivatives, pharmacology)
• Diffusion
• Disease Models, Animal
• Glioblastoma (drug therapy, pathology, radiotherapy)
• Hypoxia, Brain (drug therapy, pathology, radiotherapy)
• Kaplan-Meier Estimate
• Magnetic Resonance Imaging
• Neoplasm Transplantation
• Oxygen (metabolism)
• Radiation-Sensitizing Agents (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Temozolomide
• Vitamin A (analogs & derivatives, pharmacology)