Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1944-1954 |
Number of pages | 11 |
Journal | Cancer medicine |
Volume | 10 |
Issue number | 6 |
DOIs | |
State | Published - Mar 2021 |
Externally published | Yes |
Keywords
- 5-fluorouracil
- capecitabine
- colorectal cancer
- mTOR
- temsirolimus
ASJC Scopus subject areas
- Oncology
- Radiology Nuclear Medicine and imaging
- Cancer Research