A phase I trial of the mTOR inhibitor temsirolimus in combination with capecitabine in patients with advanced malignancies

Neel D. Trivedi, Samantha Armstrong, Hongkun Wang, Marion Hartley, John Deeken, A. Ruth He, Deepa Subramaniam, Heather Melville, Chris Albanese, John L. Marshall, Jimmy Hwang, Michael J. Pishvaian

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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 languageEnglish (US)
Pages (from-to)1944-1954
Number of pages11
JournalCancer medicine
Issue number6
StatePublished - Mar 2021


  • 5-fluorouracil
  • capecitabine
  • colorectal cancer
  • mTOR
  • temsirolimus

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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