The mTOR inhibitor everolimus in combination with carboplatin in metastatic breast cancer--a phase I trial.

Abstract

AIM:

Despite advances in the the first- and second-line treatment of metastatic breast cancer, there remains a large unmet need for additional treatment options. As preclinical studies have suggested that combining everolimus with carboplatin may produce higher activity than each drug by itself, we initiated a phase I study of this combination.

PATIENTS AND METHODS:

Patients with pre-treated metastatic breast cancer received weekly carboplatin at AUC2 and daily oral everolimus at different dose-levels (level I: 2.5 mg; II: 5 mg; III: 7.5 mg; IV: 10 mg). Three patients were assigned to dose-levels I to III, and six to dose-level IV. The primary end-point was to determine the maximum tolerated dose (MTD).

RESULTS:

Fifteen patients were recruited to the study. The median number of previous chemotherapies was four (range: 1-11). No dose-limiting toxicity occurred at levels I-III during the first cycle. Based on the pre-determined definition, the maximum planned dose-level IV was selected as the MTD. Patients received a median of four cycles of treatment (range 1-13). Most frequent grade 3 and 4 toxicities included leukopenia, thrombocytopenia and infection. Response rates were as follows: 21% partial response, 43% stable disease, and 36% progressive disease.

CONCLUSION:

Carboplatin and everolimus is a well-tolerated combination for heavily pre-treated metastatic breast cancer. Everolimus (10 mg/d) and carboplatin (AUC2 weekly) were defined as the MTD. This dose is currently being employed in an ongoing phase II trial.

• Authors: Sandra Schwarzlose-Schwarck, Christian W Scholz, Anne C Regierer, Peter Martus, Christian Neumann, Piet Habbel, Hongyu Liu, Chuanbing Zang, Jan-Hendrik Schefe, Carsten-Oliver Schulz, Kurt Possinger, Jan Eucker
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 8 Pg. 3435-41 (Aug 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22843927 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Everolimus
• Carboplatin
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Breast Neoplasms (drug therapy, pathology)
• Carboplatin (administration & dosage)
• Everolimus
• Female
• Humans
• Middle Aged
• Neoplasm Metastasis
• Sirolimus (administration & dosage, analogs & derivatives)
• TOR Serine-Threonine Kinases (antagonists & inhibitors)