In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e16504-e16504
Abstract:
e16504 Background: Pts with rCC in PIA might benefit from cDDP plus HT. Lap inhibits the intracellular tyrosine kinase domain of the epidermal growth factor receptor (EGFR) and HER2. Overexpression of EGFR and HER2 is often seen in pts with CC and might be involved in chemotherapy resistance. Besides, preclinical data suggest a synergistic effect of combining cDDP and Lap. Therefore, this phase I dose-escalation study was performed to determine the maximum tolerated dose (MTD) of Lap added to fixed doses of cDDP and HT. Methods: Pts with rCC in PIA, adequate organ function and ECOG performance status 0-1 were scheduled for 6 weekly administrations of 70 mg/m 2 cDDP plus locoregional HT. Daily Lap was added on days 1-56, starting at a dose-level of 1000 mg. The MTD was defined as the highest dose where ≤1/6 pts experienced dose-limiting toxicity (DLT). Safety, pharmacodynamics (PhD) and response were assessed. Results: Eight pts were treated. The first 4 pts (2 each at dose 1000 mg and 750 mg) experienced DLT. Of the 4 pts treated at dose level -2 (500 mg), only 1 pt was able to complete the treatment as planned, 2 pts experienced a DLT and 1 pt was not evaluable (NE), because of early progressive disease (PD) (see Table). In the evaluable pts 1 PD, 4 stable diseases and 2 partial responses (PR) were observed. One patient with PR had a resection of the local recurrence. Analysis of the resected specimen showed a pathological complete response (pCR). Enumeration of circulating endothelial cells measured at baseline and during therapy did not show consistent results. The same applied for the PhD on Ki-67, p27 Kip1 and EGFR in pretreatment and on-therapy skin biopsies. Conclusions: It is not feasible to combine Lap with fixed doses of cDDP and HT in pts with rCC in PIA mainly due to increased cDDP-related toxicity. The observed pCR is intriguing and warrants further investigation of combining HER2-blockade and cDDP/HT. Clinical trial information: NL24464.078.08. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.e16504
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
