Gene interactions and pathways from curated databases and text-mining
Breast Cancer Res Treat 2013, PMID: 23605083

A phase I trial of the IGF-1R antibody Cixutumumab in combination with temsirolimus in patients with metastatic breast cancer.

Ma, Cynthia X; Suman, Vera J; Goetz, Matthew; Haluska, Paul; Moynihan, Timothy; Nanda, Rita; Olopade, Olufunmilayo; Pluard, Timothy; Guo, Zhanfang; Chen, Helen X; Erlichman, Charles; Ellis, Matthew J; Fleming, Gini F

The mammalian target of rapamycin (mTOR) plays a critical role in promoting tumor cell growth and is frequently activated in breast cancer. In preclinical studies, the antitumor activity of mTOR inhibitors is attenuated by feedback up-regulation of AKT mediated in part by Insulin-like growth factor type 1 receptor (IGF-1R). We designed a phase I trial to determine the maximum-tolerated dose (MTD) and pharmacodynamic effects of the IGF-1R antibody Cixutumumab in combination with temsirolimus in patients with metastatic breast cancer refractory to standard therapies. A 3 + 3 Phase I design was chosen. Temsirolimus and Cixutumumab were administered intravenously on days 1, 8, 15, and 22 of a 4-week cycle. Of the 26 patients enrolled, four did not complete cycle 1 because of disease progression (n = 3) or comorbid condition (n = 1) and were replaced. The MTD was determined from the remaining 22 patients, aged 34-72 (median 48) years. Most patients (86 %) had estrogen receptor positive cancer. The median number of prior chemotherapy regimens for metastatic disease was 3. The MTD was determined to be Cixutumumab 4 mg/kg and temsirolimus 15 mg weekly. Dose-limiting toxicities (DLTs) included mucositis, neutropenia, and thrombocytopenia. Other adverse events included grade 1/2 fatigue, anemia, and hyperglycemia. No objective responses were observed, but four patients experienced stable disease that lasted for at least 4 months. Compared with baseline, there was a significant increase in the serum levels of IGF-1 (p < 0.001) and IGFBP-3 (p = 0.019) on day 2. Compared with day 2, there were significant increases in the serum levels of IGF-1 (p < 0.001), IGF-2 (p = 0.001), and IGFBP-3 (p = 0.019) on day 8. A phase II study in women with metastatic breast cancer is ongoing.

Diseases/Pathways annotated by Medline MESH: Breast Neoplasms, Neoplasm Metastasis
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Text Mining Data

AKT → Insulin-like growth factor: " In preclinical studies, the antitumor activity of mTOR inhibitors is attenuated by feedback up-regulation of AKT mediated in part by Insulin-like growth factor type 1 receptor ( IGF-1R ) "

mTOR → AKT: " In preclinical studies, the antitumor activity of mTOR inhibitors is attenuated by feedback up-regulation of AKT mediated in part by Insulin-like growth factor type 1 receptor ( IGF-1R ) "

Manually curated Databases

No curated data.