Since our excellent review of Temodar by Andrew Parker was completed in June, 2000, there have been many journal articles and abstracts presented on Temodar. We will list a brief synopsis, with a link to the reference (or abstract if available) of the most important ones here. Check back for updates. The most recently added ones will be at the top!
Phase I Study of Temozolomide and Thalidomide in the Treatment of Metastatic Melanoma.
This study was designed to find the maximum tolerated dose of Thalidomide and Temozolomide. It was a dose escalation study, starting Thalidomide out at 200mg/day (100mg/day for elderly patients) and going up to 400mg/day (250mg/day in the elderly), and Temodar at 50mg/m2/day for 6 weeks on and 4 weeks off, and going up to 75mg/m2/day for 6 weeks on and 4 weeks off.
They found that the maximum dose that they tested was relatively safe with no major toxcicity. Of the 9 patients whose response could be evaluated, 1 had a partial response, 3 had minor response, 1 had a mixed response, 2 had stable disease, and only 2 showed progression. Of the 2 who showed progression, both patiented were at the lowest dose of both drugs tests.
Conclusion: This combination is well tolerated and has anti-tumor response in patients with metastatic melanoma. An ongoing phase 2 study will establish the efficacy of this combination.
Phase I/II Trial of Gliadel Plus Temodar for Adult Patients with Recurrent High-Grade Glioma.
This study shows that it is safe to use Temodar after implanting Gliadel wafers. A dose escalation of Temodar was done - to make sure that there were no bad interactions between Gliadel and Temodar. They started Temodar at 100mg/m2/day and went up to 200mg/m2/day - which is the maximum usual dose used. They found no significant problems. There were 13 patients, 9 with GBM and 4 with AA. One patient had a severe hematologic problem, which resolved when the Temodar was discontinued. Early results show 9 patients achieved stable disease, for 1-12 cycles of Temodar. They concluded that Gliadel followed by Temodar appears to be well tolerated with encouraging although preliminary, response rates.
Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy.
The standard treatment of anaplastic ologiodendrogliomas (AO) and oligoastrocytmoa (AOA) has historically been a combination of 3 drugs called PCV, which yields a response rate of about 80%. This study tests the use of Temodar for 48 patients in whom PCV doesn't work or who have recurrences while on PCV. They used the standard schedule of 150 to 200mg/m2/day for 5 days in a 28 day cycle. Results:16.7% had a complete response, 27.1% had a partial response and 39.6% had stable disease. Overall survival was 10 months, but for the group who had complete responses, the overall survival was more than 26 months. CONCLUSION: Temozolomide is safe and effective in the treatment of recurrent AO and AOA.
A Phase II Study of Temozolomide for Recurrent Brain Metastases.
This study reports on the use of Temodar with brain metastases. There were 36 patients with a median age of 60 (36-77). The primary tumor types were: Lung (58%), breast (25%), melanoma (8%), rectal (6%) and endometrial (3%).
Results: 2 partial response (8%), 9 stable disease (35%), and 15 progression.
Conclusion: These preliminary results indicate that temozolomide is safe and well tolerated in this patient population. While radiographic response is uncommon more than one third of patients have stabilization of their progressive brain metastases. Time to progression and survival data are being analyzed.
Multi-Institutional Trial of BID Regimen of Temozolomide for Recurrent Malignant Gliomas
(Note: BID means "twice a day")
This abstract presents an alternative dosing schedule for Temodar: Twice a day for 5 days, then off for 23 days. They start with 200mg/m2 with the first dose, then 90mg/m2 every 12 hours for the next 9 doses of the cycle. The reasoning behind this is to try to reduce resistance to the drug. It is thought that resistance develops because of elevated levels of an enzyme called 06-alkylguanine alkyltransferase (AGAT). They are trying to get a dose-dependent AGAT depletion, which would increase the effectiveness of the drug. Background: 63 patients were enrolled: 31 with glioblastoma multiforme(GBM), 13 with anaplastic oligodendroglioma (AO), 12 with anaplastic Astrocytoma (AA). 44 patients were evaluable. Results: Overall response rate at 2 cycles (of all tumor types) was 77%.
4% of patients with GBM and 9% with AA had a complete response. 4 patients (they did not specify the tumor type) had stable disease on MRI. Median progression free survival time was 5.5 months (3.18-7.65 months).
Conclusions: A BID regimen of Temozolomide is tolerated will by most patients. Response rates are promising.
Phase II Trial of Temozolomide (Temodar®) in Patients with Progressive or Recurrent Low Grade Glioma.
This is the report of a phase 2 trial. The standard schedule was used: 200mg/m2/day for 5 days in a 28 day cycle. There were 39 patients: 18 astrocytomas, 15 oligodendroglioma, 2 mixed gliomas, and 4 had pilocytic astrocytomas one of which involved the optic chiasm. Results: Twenty-four patients demonstrate stable disease (for up to 27+ months), nine had progressive disease, two was unable to be evaluated, and four are too early for evaluation. Conclusion: These initial results suggest that Temozolomide may be active in the treatment of LGG and warrant further evaluation of this agent in the treatment of these tumors.
A Phase II Trial of Primary Chemotherapy with Temozolomide in Patients with Low-Grade Cerebral Gliomas.
25 patients, 12 male, 13 female, median age= 39. 18 had grade 2 astrocytoma, 7 with low grade oligodendroglioma.
9 Of 10 patients who had symptoms (such as recurrent seizures) had clinical benefit with improvement of symptoms and health quality of life scores.
Of the 12 patients who received at least 6 cycles 3/12 had a partial response, 5/12 had Minor Response and 3/12 Stable Disease.
Only 2/23 of the patients had PD. Conclusion: Preliminary results of this ongoing trial suggest that Temozolomide has single agent activity in the treatment of patients with low grade cerebral glioma.