A multicenter trial evaluating retaspimycin HCL (IPI-504) plus trastuzumab in patients with advanced or metastatic HER2-positive breast cancer
| Autor: | José Baselga, Clifford A. Hudis, Reshma Mahtani, Joyce O'Shaughnessy, Shanu Modi, Eduardo Rodenas, Nan Lin, Charles Henderson, Jill Goddard, Cristina Saura |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Receptor ErbB-2 Nausea Lactams Macrocyclic Breast Neoplasms Antibodies Monoclonal Humanized Phase 2 Gastroenterology Disease-Free Survival HER2+ MBC Breast cancer Trastuzumab Internal medicine Multicenter trial Antineoplastic Combined Chemotherapy Protocols Benzoquinones Humans Medicine Adverse effect Aged Retaspimycin plus trastuzumab business.industry Metastatic liver disease Middle Aged medicine.disease Clinical Trial Hypokalemia Surgery Clinical trial Treatment Outcome Oncology Female medicine.symptom business medicine.drug |
| Zdroj: | Breast Cancer Research and Treatment |
| ISSN: | 1573-7217 0167-6806 |
| DOI: | 10.1007/s10549-013-2510-5 |
| Popis: | Heat shock protein 90 (Hsp90) facilitates maturation and stability of HER2. Combining an Hsp90 inhibitor and trastuzumab has demonstrated anti-tumor effects in patients with HER2+ breast cancer. Adults with measurable, locally advanced or metastatic HER2+ breast cancer and prior trastuzumab treatment were enrolled in a phase 2 trial employing weekly 300 mg/m(2) retaspimycin HCl, a potent Hsp90 inhibitor, with 6 mg/kg trastuzumab every 3 weeks. A Simon's two-stage design determined trial expansion by dose-limiting toxicity (DLT) and response rates. Pharmacokinetics and electrocardiograms were evaluated. Twenty-six patients with median age 52.5 years (range 33-72) enrolled with a median of six prior chemotherapeutic regimens (range 2-20). On study, patients received a median of three treatment cycles (range 1-12). No DLTs were observed. Most adverse events (AEs) were grade 1 or 2; common treatment-related AEs included fatigue (46 %), nausea (31 %), and diarrhea (23 %). One patient had treatment-related serious AEs of grade 1 diarrhea and grade 3 hypokalemia. grade 3 transaminase elevation occurred in one patient (4 %) who also had metastatic liver disease. Sixteen patients (62 %) had stable disease, with a median on-study duration of 2.4 months (range 1.1-8.2). No confirmed responses were observed. Retaspimycin HCl at 300 mg/m² weekly in combination with trastuzumab was well tolerated and without significant toxicities. Modest clinical activity was observed, but did not meet criteria for trial expansion. The safety profile for patients on study raises the possibility of retaspimycin HCl underdosing that limited efficacy. Studies employing higher doses are ongoing. |
| Databáze: | OpenAIRE |
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