Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cancer+Chemother+Pharmacol 2016 ; 77 (5): 973-7 Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Phase I Dose Escalation Study of Temsirolimus in Combination with Metformin in Patients with Advanced/Refractory Cancers #MMPMID27014780
Khawaja MR; Nick AM; Madhusudanannair V; Fu S; Hong D; McQuinn LM; Ng CS; Piha-Paul SA; Janku F; Subbiah V; Tsimberidou A; Karp D; Meric-Bernstam F; Lu KH; Naing A
Cancer Chemother Pharmacol 2016[May]; 77 (5): 973-7 PMID27014780show ga
Purpose: mTOR inhibitors like temsirolimus may result in undesirable AKT upregulation. Metformin inhibits mTOR through different mechanisms and may enhance temsirolimus?s antitumor activity. We conducted an open-label phase I dose escalation trial of this drug combination in patients with advanced/refractory cancers. Methods: Temsirolimus, 25 mg weekly, was combined with an escalating daily dose of metformin (level 1: 500; level 2: 1000; level 3: 1500; level 4: 2000 mg) by utilizing a standard 3+3 trial design. Treatment was administered in 28-day cycles following initial two-week metformin titration during the first cycle. Results: Twenty-one patients (median age, 56 years) with sarcoma (n=8), colorectal (n=3), endometrial (n=4), uterine carcinosarcoma (n=2), ovarian (n=2), and other (n=2) cancers were enrolled. Patients had received median of 4 prior systemic treatments. Two dose limiting toxicities were observed (grade 3 mucositis, grade 3 renal failure); both patients continued treatment after dose modification. Fifty-six percent patients had stable disease as best response; clinical benefit rate was 22%. Patients continued treatment for median of 11 weeks. Conclusions: Combination temsirolimus/metformin was well tolerated with modestly promising effectiveness among this heavily pretreated patient cohort. We recommend a dose of temsirolimus 25 mg weekly and metformin 2000 mg daily for phase II study.