In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 4586-4586
Abstract:
4586 Background: Neoadjuvant chemotherapy (NC) preceding radical cystectomy (RC) is an accepted standard for miUCB patients (pts). Dasatinib (D) is an oral tyrosine kinase inhibitor of Src mediated signaling, and has demonstrated promising preclinical anti-tumor activity, providing a rationale to evaluate Neo-D in human miUCB. Methods: A phase II trial was conducted to assess the safety and biologic activity of Neo-D in miUCB. Key eligibility criteria included: miUCB (T2-T4a, N0, M0), unsuitable or willing to forego platinum-based NC, adequate TURBT tissue available, ECOG PS 0-1, creatinine 〈 2 x ULN. Pts received D 100 mg po once daily for 28 +/- 7 days followed by RC 8-24 hours after the last dose. The primary endpoint was feasibility defined as 〉 60% of pts completing therapy without treatment-related dose limiting toxicity (DLT) specified as grade 4 hematologic toxicity, grade 3 non-hematologic toxicity, or any grade 2 toxicity 〉 14 days. Secondary endpoints included the assessment of biologic activity as assessed by pre- and post-treatment tumor tissue immunohistochemistry analysis of Src, pSrc, EPHA2, pEPHA2, FAK, pFAK, AKT, pAKT, CD31, Ki67, TUNEL. Results: The study completed accrual with enrollment of 25pts. 22 and 24 pts were respectively evaluable for feasibility and toxicity endpoints. Patient demographics included: median age – 62, M/F – 20/5, ECOG PS 0/1 – 19/6. Baseline tumor staging included: T2 – 17, T3 – 7. The study achieved its primary endpoint with 15 pts (68%) completing therapy without treatment related DLT’s. DLT’s included: fatigue (2 pts), DVT/PE, abdominal pain, supraventricular tachycardia, enteric fistula, and hematuria (1 pt each). Frequency of highest observed toxicity on study included: Grade 1 – 13%, Grade 2 – 38%, Grade 3 – 46%, Grade 4 – 4%. Among 22 patients, pathologic stage at RC was T1/Tis in 3 pts (14%), ≥T2 in 19 pts (86%), and node positive in 6 pts (27%). Correlative analyses of pre- and post-treatment tumor Src signaling are ongoing and will be updated at the meeting. Conclusions: Neoadjuvant dasatinib preceding RC is feasible in miUCB patients. Tumor tissue correlative studies may provide directions for further development.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.4586
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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