Therapeutic activity of 7-[(2-trimethylsilyl)ethyl)]-20 (S)-camptothecin against central nervous system tumor-derived xenografts in athymic mice.

Abstract

PURPOSE:

Camptothecins have emerged as an important new class of antitumor drugs. Camptothecin derivatives such as CPT-11 and topotecan are commercially available and approved for the treatment of colorectal (CPT-11) and ovarian and small-cell lung cancer (topotecan). This study was designed to test the efficacy of karenitecin, a novel highly lipophilic camptothecin derivative, against a panel of human tumor xenografts derived from adult and pediatric central nervous system malignancies growing in athymic nude mice.

METHODS:

Xenografts evaluated were derived from childhood high-grade gliomas (D-212 MG, D-456 MG), adult high-grade gliomas (D-54 MG, D-245 MG), medulloblastomas (D-341 MED, D-487 MED), and ependymomas (D-528 EP, D-612 EP), as well as sublines with demonstrated resistance to procarbazine (D-245 MG (PR)) and busulfan (D-456 (BR)). In replicate experiments, karenitecin was given at 1.0 mg/kg per dose via intraperitoneal injection for a period of 10 consecutive days, which is the dosage lethal to 10% of treated animals.

RESULTS:

Karenitecin produced statistically significant (P < or = 0.001) growth delays in all subcutaneous xenografts tested, including the sublines resistant to procarbazine and busulfan. Growth delays ranged from 12.1 days in D-456 MG (BR) to 90+ days in D-212 MG and D-341 MED. Karenitecin also produced statistically significant (P < or = 0.001) increases in survival of animals bearing D-341 MED intracranial xenografts (69% increase) and those bearing D-456 MG xenografts (62% increase).

CONCLUSION:

These preclinical studies confirm that karenitecin is active against human central nervous system xenografts and should undergo clinical evaluation in patients with malignant central nervous system tumors.

• Authors: S T Keir, F Hausheer, A A Lawless, D D Bigner, H S Friedman
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 48 Issue 1 Pg. 83-7 (Jul 2001) ISSN: 0344-5704 [Print] Germany
• PMID: 11488529 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• cositecan
• Irinotecan
• Camptothecin

Topics

• Animals
• Antineoplastic Agents, Phytogenic (adverse effects, therapeutic use)
• Brain Neoplasms (drug therapy)
• Camptothecin (analogs & derivatives, pharmacology, therapeutic use)
• Female
• Humans
• Irinotecan
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Transplantation, Heterologous