Intralesionally implanted cisplatin plus systemic carmustine for the treatment of brain tumor in rats
✍ Scribed by Kong, Qingzhong; Kleinschmidt-DeMasters, Bette K.; Lillehei, Kevin O.
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 100 KB
- Volume
- 69
- Category
- Article
- ISSN
- 0022-4790
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✦ Synopsis
Background and Objectives:
The benefit of conventional chemotherapy for the treatment of malignant brain tumors, although limited, is real. A major obstacle in the treatment of these lesions is the ability to deliver drug across the blood-brain barrier (BBB). Local drug implantation, circumventing the BBB, has been a useful strategy for treatment of intracranial lesions, and may work synergistically with systemic chemotherapy. To test this hypothesis, either intraperitoneal (ip) carmustine or cisplatin was combined with the intracranial (ic) administration of polymerdelivered cisplatin in rats with intracranial tumors. Methods and Results: 9L gliosarcoma tumor cells (5 × 10 3 ) were administered through a right frontal lobe cannula in rats 7 days prior to treatments. Cisplatin-loaded biodegradable polymer was then administered via the cannula, with free cisplatin or carmustine injected ip. Animals were monitored for 60 days post-treatment. In experiment 1, ic cisplatin at a dose of 0.5, 1.0, 2.0, and 4.0 mg/m 2 resulted in a mean survival time of 34 ± 3, 39 ± 14, 47 ± 11, and 31 ± 20 days (MST ± SD), respectively, compared to 26 ± 4 days in the control group and 30 ± 7 days in the group treated with 50 mg/m 2 ip free cisplatin. In experiment 2, ip free cisplatin at 25, 40, 50, and 100 mg/m 2 resulted in a MST of 28 ± 3, 30 ± 4, 32 ± 3, and 14 ± 8 days, respectively, compared to 26 ± 1 days in the control group. In experiment 3, the MST in the groups treated with 0.5 mg/m 2 of ic cisplatin, 25 mg/m 2 of ip cisplatin, 10 mg/kg of ip carmustine, ic cisplatin (0.5 mg/m 2 ) plus ip cisplatin (25 mg/m 2 ), and ic cisplatin (0.5 mg/m 2 ) plus ip carmustine (10 mg/kg) was 30 ± 4 days (P > 0.05), 28 ± 2 (P > 0.05), 36 ± 4 (P < 0.01), 32 ± 3 (P < 0.01), and 50 ± 11 days (P < 0.01), respectively, compared to the tumor control group (26 ± 1 days). Long-term survivors (29%) were seen only in the ic cisplatin plus ip carmustine group. Additive toxicity was not observed. Conclusions: Intralesional polymer-delivered (ic) cisplatin plus systemic (ip) carmustine is highly effective for the treatment of intracranial 9L gliosarcoma in tumors.