A phase I study of temsirolimus and metformin in advanced solid tumours.
The purpose of this phase I trial was to establish the maximum tolerated dose and define the dose-limiting toxicities of a combination of temsirolimus and metformin. Patients with advanced solid tumours who had exhausted standard treatment options were eligible. Treatment included weekly intravenous temsirolimus and daily oral metformin. Eleven patients were enrolled. Dose-limiting toxicities were observed in all patients at the initial dose level of 25 mg weekly of temsirolimus and metformin 500 mg po BID. At dose level -1, 2 of 8 patients experienced dose-limiting toxicities. Toxicities included grade 4 pneumonitis, persistent grade 3 fatigue, and thrombocytopenia requiring dose delays. The maximum tolerated dose (level -1) was 20 mg temsirolimus weekly and 500 mg po daily of metformin. One patient with head and neck cancer experienced a partial response. Five patients had stable disease including a patient with melanoma who had stable disease for 22 months.
MacKenzie
Mary J
MJ
London Health Sciences Centre, 790 Commissioners Rd. East, London, ON, Canada N6A 4L6. Mary.mackenzie@lhsc.on.ca
Ernst
Scott
S
Johnson
Craig
C
Winquist
Eric
E
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009864:Ontario; D010865:Pilot Projects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D008687:Metformin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus