Sorafenib, Ratamu2 and Thalidomide for GBM4 that hasn't

mosey · Regular Joined: 10 Dec 2006 Posts: 15

responded to Temodar and radiation.

My brother's Feb 20th MRI showed that another tumor had sprouted next to the original one one month following the temodar and radiation. The oncologist tried for the past month a continuation of the temodar along with a once per month drip of iranotecan.

The March 20th MRI showed the tumor is continuing to grow, now at 6.1 centimeters. They discontinued the temodar and iranotecan, and now want to try the above listed experimental drugs.

I can't find any information at all regarding Ratamu2 anywhere online.

Does anyone have any familiarity with this medication?

Thanks for any info you may have.

My brother has been doing reasonably well, but this looks very bad at this time.

Any responses would be appreciated.

Thanks and best wishes for all!

mosey · Regular Joined: 10 Dec 2006 Posts: 15

I found out it's Rapamu2, also known as rapamune.

Still wondering if anyone has any experience with using these meds?

thanks

Kris

Hi Mosey,

Rapamune is used together with cyclosporine and a steroid medication to prevent your body from rejecting a kidney transplant. It suppresses the body’s immune system.
Sorafenib is used in renal cell carcinoma or kidney cancer.
Thalidomide is a sedative, anti-inflammatory drug (teratogenic!). Currently, there are studies underway to determine the drug's effects in several types of cancers.

I don't know how this trio is being under investigation for GBM patients, you should ask your borther's physician to explain you more about this combination, what do they expect and what are the available results in GBM?

I know that soranefib may have an effect on the tumor angiogenesis, i.e. reducing or blocking the blood supply to the tumor.

I'm sure his treating physician could give you reassuring advice.

Keep strong, you are in my thoughts.

Kris

hl1098 · New User Joined: 28 Feb 2007 Posts: 4

Hi,

I do not have experience using the drug, but have done some reading on it regarding its use on brain tumor.

Rapamune is commonly referred as rapamycin (sirolimus). It was originally developed as an immunosuppressant drug. It was later found to be a potent inhibitor of a protein called mTOR, which is frequently activated in a number of cancers including glioblastoma. Both Dana-Farbar and Duke have tried using rapamycin in combination with an EGFR inhibitor for glioma (abstracts pasted below). The results were encouraging. More clinical trials were going on using other mTOR inhibitors such as CCI 779, RAD001, AP23573. They all look like rapamycin in structure. The treatment was thought to be more effective for patients who have lost PTEN-expression.

Bert regards,

Hong

Neurology. 2006 Jul 11;67(1):156-8. Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas.Doherty L, Gigas DC, Kesari S, Drappatz J, Kim R, Zimmerman J, Ostrowsky L, Wen PY. Center for Neuro-Oncology, Dana Farber/Brigham and Women's Cancer Center, Boston, MA 02115, USA.
Malignant gliomas are frequently characterized by amplification of the epidermal growth factor receptor (EGFR) and loss of PTEN tumor suppressor gene. Twenty-eight heavily pretreated patients with recurrent malignant gliomas were administered EGFR inhibitors (gefitinib or erlotinib) in combination with the mTOR (mammalian target of rapamycin) inhibitor sirolimus. The regimens were reasonably well tolerated. Nineteen percent of patients experienced a partial response and 50% had stable disease. Six-month progression-free survival for glioblastoma patients was 25%.

Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):860-8. Phase 1 trial of gefitinib plus sirolimus in adults with recurrent malignant glioma.Reardon DA, Quinn JA, Vredenburgh JJ, Gururangan S, Friedman AH, Desjardins A, Sathornsumetee S, Herndon JE 2nd, Dowell JM, McLendon RE, Provenzale JM, Sampson JH, Smith RP, Swaisland AJ, Ochs JS, Lyons P, Tourt-Uhlig S, Bigner DD, Friedman HS, Rich JN. AstraZeneca Pharmaceuticals, Wilmington, Delaware, USA. reard003@mc.duke.edu
PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gefitinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent malignant glioma. PATIENTS AND METHODS: Gefitinib and sirolimus were administered on a continuous daily dosing schedule at dose levels that were escalated in successive cohorts of malignant glioma patients at any recurrence who were stratified based on concurrent use of CYP3A-inducing anticonvulsants [enzyme-inducing antiepileptic drugs, (EIAED)]. Pharmacokinetic and archival tumor biomarker data were also assessed. RESULTS: Thirty-four patients with progressive disease after prior radiation therapy and chemotherapy were enrolled, including 29 (85%) with glioblastoma multiforme and 5 (15%) with anaplastic glioma. The MTD was 500 mg of gefitinib plus 5 mg of sirolimus for patients not on EIAEDs and 1,000 mg of gefitinib plus 10 mg of sirolimus for patients on EIAEDs. DLTs included mucositis, diarrhea, rash, thrombocytopenia, and hypertriglyceridemia. Gefitinib exposure was not affected by sirolimus administration but was significantly lowered by concurrent EIAED use. Two patients (6%) achieved a partial radiographic response, and 13 patients (38%) achieved stable disease. CONCLUSION: We show that gefitinib plus sirolimus can be safely coadministered on a continuous, daily dosing schedule, and established the recommended dose level of these agents in combination for future phase 2 clinical trials.

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