| Abstract | PURPOSE: To investigate the safety and pharmacokinetics (PK) of combined treatment with letrozole and the oral mTOR inhibitor RAD001 in patients with metastatic breast cancer stable or progressing after > or = 4 months on letrozole alone. METHODS: Eighteen patients received letrozole (2.5 mg/day) and RAD001 at 5 mg/day (cohort 1) or 10 mg/day (cohort 2). In the absence of DLT in cohort 1, cohort 2 was expanded to 12 patients to obtain additional safety and PK data. RESULTS: Most common adverse events were stomatitis (50.0% of patients), fatigue (44.4%), anorexia and/or decreased appetite (44.4%), diarrhoea (38.9%), headache (33.3%) and rash (33.3%). There was 1 DLT, a grade 3 thrombocytopaenia in cohort 2. No clinically relevant PK interaction was detected. Seven patients received the combination therapy for >6 months. One patient had a complete response, and one had a 28% reduction in liver metastases, both in cohort 2. CONCLUSION: Daily therapy with RAD001 plus letrozole is promising: the results suggest anti-tumour activity with no PK interactions. The overall safety profile of the combination is consistent with that expected for RAD001 monotherapy. A daily dose of RAD001 10mg is recommended for further trials. |
| Authors | Ahmad Awada, Fatima Cardoso, Christel Fontaine, Luc Dirix, Jacques De Grève, Christos Sotiriou, Jutta Steinseifer, Carine Wouters, Chiaki Tanaka, Ulrike Zoellner, Pui Tang, Martine Piccart
(Affiliation: Medical Oncology Clinic, Institut Jules Bordet, Brussels, Belgium. ahmad.awada at bordet.be)
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| Journal | European journal of cancer (Oxford, England : 1990)
(Eur J Cancer)
Vol. 44
Issue 1
Pg. 84-91
(Jan 2008)
ISSN: 0959-8049 England |
| PMID | 18039566
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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| Chemical References |
- Immunosuppressive Agents
- Nitriles
- Triazoles
- letrozole
- everolimus
- Sirolimus
|
| Topics |
- Administration, Oral
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, pharmacokinetics, therapeutic use)
- Breast Neoplasms
(drug therapy)
- Cohort Studies
- Drug Interactions
- Feasibility Studies
- Female
- Humans
- Immunosuppressive Agents
(administration & dosage, adverse effects, pharmacokinetics)
- Male
- Middle Aged
- Nitriles
(administration & dosage, adverse effects, pharmacokinetics)
- Sirolimus
(administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
- Treatment Outcome
- Triazoles
(administration & dosage, adverse effects, pharmacokinetics)
|
