BACKGROUND: Temsirolimus is an mTOR antagonist with proven anticancer efficacy. 
Preclinical data suggest greater anticancer effect when mTOR inhibitors are 
combined with cytotoxic chemotherapy. We performed a Phase I assessment of the 
combination of temsirolimus and capecitabine in patients with advanced solid 
tumors.
METHODS: Patients were enrolled in an alternating dose escalation of 
temsirolimus (at 15 or 25 mg IV weekly) and capecitabine (at 750, 1000, and 
1250 mg/m2 twice daily) in separate Q2-week and Q3-week cohorts. At the 
recommended Phase II doses (RP2Ds) of temsirolimus and capecitabine (Q2), seven 
patients were also treated with oxaliplatin (85 mg/m2 , day 1) to determine 
triplet combination safety and efficacy.
RESULTS: Forty-five patients were enrolled and 41 were evaluable for 
dose-limiting toxicities (DLTs). The most common adverse events (AEs) were 
mucositis, fatigue, and thrombocytopenia. The most common grade 3/4 AEs were 
hypophosphatemia and anemia. Five patients had DLTs, including hypophosphatemia, 
mucositis, and thrombocytopenia. The RP2Ds were temsirolimus 25 mg +capecitabine 
1000 mg/m2 (Q2); and temsirolimus 25 mg +capecitabine 750 mg/m2  (Q3). Of the 38 
patients evaluable for response, one had a partial response (PR) and 19 had 
stable disease (SD). The overall disease control rate was 52%. Five of the 20 
patients with SD/PR maintained disease control for >6 months.
CONCLUSIONS: The combination of temsirolimus and capecitabine is safe on both a 
Q2-week and a Q3-week schedule. The combination demonstrated promising evidence 
of disease control in this highly refractory population and could be considered 
for testing in disease-specific phase II trials.