Wednesday, September 24, 2008

I approve this message

Got a call for Dr. S last night -- Ariad's doctors agree, my scans are stable enough to enroll in the deforolimus trial. She also mentioned that she had been e-mailing with my NY doctor, and he was also on-board with the decision to take a shot at the trial. So I'm going to go for it sometime next week after I finish a course of antibiotics I'm taking. 

I'll have much, much, much more about the drug and trial in upcoming weeks. Probably not so much the substance of it, but the psychology. In the meantime, here's an abstract (emphasis added) of an encouraging deforolimus sarcoma trial published in January:

Phase I trial of the novel mammalian target of rapamycin inhibitor deforolimus (AP23573; MK-8669) administered intravenously daily for 5 days every 2 weeks to patients with advanced malignancies.

Mita MM, Mita AC, Chu QS, Rowinsky EK, Fetterly GJ, Goldston M, Patnaik A, Mathews L, Ricart AD, Mays T, Knowles H, Rivera VM, Kreisberg J, Bedrosian CL, Tolcher AW.
Cancer Therapy and Research Center, Institute for Drug Development, The University of Texas Health Science Center, San Antonio, TX, USA.
PURPOSE: This phase I trial was conducted to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of deforolimus (previously known as AP23573; MK-8669), a nonprodrug rapamycin analog, in patients with advanced solid malignancies. 
PATIENTS AND METHODS: Patients were treated using an accelerated titration design with sequential escalating flat doses of deforolimus administered as a 30-minute intravenous infusion once daily for 5 consecutive days every 2 weeks (QDx5) in a 28-day cycle. Safety, pharmacokinetic, pharmacodynamic, and tumor response assessments were performed. 
RESULTS: Thirty-two patients received at least one dose of deforolimus (3 to 28 mg/d). Three dose-limiting toxicity events of grade 3 mouth sores were reported. The maximum-tolerated dose (MTD) was 18.75 mg/d. Common treatment-related adverse events included reversible mouth sores and rash. Whole-blood clearance increased with dose. Pharmacodynamic analyses demonstrated mammalian target of rapamycin inhibition at all dose levels. Four patients (one each with non-small-cell lung cancer, mixed müllerian tumor [carcinosarcoma], renal cell carcinoma, and Ewing sarcoma) experienced confirmed partial responses, and three additional patients had minor tumor regressions. 
CONCLUSION: The MTD of this phase I trial using an accelerated titration design was determined to be 18.75 mg/d. Deforolimus was well tolerated and showed encouraging antitumor activity across a broad range of malignancies when administered intravenously on the QDx5 schedule. On the basis of these overall results, a dose of 12.5 mg/d is being evaluated in phase II trials.


Sachin Palewar said...

What's your opinion on Tarceva?

SG said...

Don't really have one. I know there's a sarcoma trial for tarceva in the US (maybe in conjunction w/ temodar/temozolomide?), but I don't see any published results. Is this something you are considering? Have your wife's doctors had some good luck with it?