Abstract 28: Phase I trial of combined temsirolimus, erlotinib, and cisplatin in advanced solid tumors
| Autor: | Ramona Jayasena, Dawn L. Hershman, Kevin Kalinsky, Ying-Ka Lau, Katherine D. Crew, Ramon Parsons, Julia Forman, Matthew A. Maurer |
|---|---|
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cancer Research. 73:28-28 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | A large subset of triple negative breast cancers (TNBC) are driven in part by a combination of activated growth factor signaling and downstream constitutive activation of the PI3K pathway. We have hypothesized that targeting the EGFR, PTEN and DNA damage pathways simultaneously with the rapalog temsirolimus, the EGFR inhibitor erlotinib, and cisplatin may provide therapeutic benefit in a definable subset of TNBC patients. As an initial step we conducted a single institution phase one dose escalation trial to test the tolerability of combined temsirolimus, erlotinib, and cisplatin in patients with advanced solid tumors. The trial accrued nine patients between August 2010 and May 2012. Cisplatin was given at a dose of 30 mg/m2 while the starting doses of erlotinib and temsirolimus were 100 mg and 15 mg, respectively. Cisplatin and temsirolimus were administered on days 1 and 8 of 21 day cycles and erlotinib was taken daily. The trial incorporated a standard anti-emetic regimen, dispensed prn scripts for loperamide at treatment start, and utilized a prophylactic rash treatment strategy with doxycycline given 100 mg bid for at least the first six weeks of treatment. Two of the six patients in dose level one experienced a DLT within the first week of treatment (dyspnea and mucositis, respectively). Three additional patients were then accrued at the de-escalated dose level in which erlotinib was dose-reduced to 75 mg, without a DLT. Among the seven patients that did not experience a DLT, total time on treatment is listed in order of accrual (14, 14, 6, 31, 38, 20, and 15 weeks). Six stopped treatment due to PD and one stopped due to intolerance (increased edema). Frequent dose delays due to thrombocytopenia occurred in one patient (20% of planned treatments) at dose level one and one patient at the de-escalated dose level (38% of planned treatments). Infrequent causes of dose delays included fatigue, mucositis, neutropenia, and increased serum creatinine. Frequent grade 2 adverse events thought to be likely or definitely caused by study drugs included, hypomagnesemia, hypokalemia, anemia, and increased serum creatinine. Rash, nausea, and diarrhea were all well controlled. Of the six patients evaluable for response, three had colorectal cancer and three had breast cancer. One PR was seen in a patient with TNBC treated on the de-escalated dose level but the response was short lived (eight weeks) due to PD in the skin. The average number of prior treatment regimens was 4 (range 1 to 6). Translational studies are ongoing. In conclusion, the combination of cisplatin at 30 mg/m2, temsirolimus at 15mg, and erlotinib at 75 mg was well tolerated. Given the known genetic lesions in TNBC, this novel drug combination may be reasonable to test in a pick-the-winner phase 2 randomized trial with incorporated futility testing. Citation Format: Matthew A. Maurer, Kevin Kalinsky, Katherine Crew, Ramona Jayasena, Julia Forman, Ying-Ka Lau, Ramon Parsons, Dawn Hershman. Phase I trial of combined temsirolimus, erlotinib, and cisplatin in advanced solid tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 28. doi:10.1158/1538-7445.AM2013-28 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|