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Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma.

Publication ,  Journal Article
Reardon, DA; Vredenburgh, JJ; Desjardins, A; Peters, KB; Sathornsumetee, S; Threatt, S; Sampson, JH; Herndon, JE; Coan, A; McSherry, F ...
Published in: J Neurooncol
July 2012

To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of dasatinib, an inhibitor of the Src family kinase proteins, with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, among recurrent malignant glioma patients. Once daily dasatinib was escalated in successive cohorts while erlotinib was administered daily at established doses based on concurrent CYP3A-inducing anticonvulsant (EIAEDS) use. Dasatinib pharmacokinetic analyzes were performed. Forty-seven patients enrolled including 37 (79 %) with grade IV and 10 (21 %) with grade III malignant glioma. Thirty patients (64 %) were at ≥second recurrence, while 27 (57 %) had received prior bevacizumab. The dasatinib MTD was 180 mg when combined with either 150 mg of erlotinib for patients not on EIAEDs, or 450 mg of erlotinib for patients on EIAEDs. The most common DLTs were diarrhea and fatigue, while most adverse events were grade 2. Pharmacokinetic data suggests that dasatinib exposure increased with increased dasatinib dose and concurrent erlotinib administration, while concurrent EIAED use diminished dasatinib exposure. No radiographic responses were observed, and only one patient (2 %) remained progression-free at 6 months. We demonstrate that dasatinib plus erlotinib can be safely co-administered on a continuous, daily dosing schedule with erlotinib, and established the recommended dose level of this combination.

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Published In

J Neurooncol

DOI

EISSN

1573-7373

Publication Date

July 2012

Volume

108

Issue

3

Start / End Page

499 / 506

Location

United States

Related Subject Headings

  • Young Adult
  • Tissue Distribution
  • Thiazoles
  • Quinazolines
  • Pyrimidines
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Maximum Tolerated Dose
 

Citation

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Reardon, D. A., Vredenburgh, J. J., Desjardins, A., Peters, K. B., Sathornsumetee, S., Threatt, S., … Friedman, H. S. (2012). Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma. J Neurooncol, 108(3), 499–506. https://doi.org/10.1007/s11060-012-0848-x
Reardon, David A., James J. Vredenburgh, Annick Desjardins, Katherine B. Peters, Sith Sathornsumetee, Stevie Threatt, John H. Sampson, et al. “Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma.J Neurooncol 108, no. 3 (July 2012): 499–506. https://doi.org/10.1007/s11060-012-0848-x.
Reardon DA, Vredenburgh JJ, Desjardins A, Peters KB, Sathornsumetee S, Threatt S, et al. Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma. J Neurooncol. 2012 Jul;108(3):499–506.
Reardon, David A., et al. “Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma.J Neurooncol, vol. 108, no. 3, July 2012, pp. 499–506. Pubmed, doi:10.1007/s11060-012-0848-x.
Reardon DA, Vredenburgh JJ, Desjardins A, Peters KB, Sathornsumetee S, Threatt S, Sampson JH, Herndon JE, Coan A, McSherry F, Rich JN, McLendon RE, Zhang S, Friedman HS. Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma. J Neurooncol. 2012 Jul;108(3):499–506.
Journal cover image

Published In

J Neurooncol

DOI

EISSN

1573-7373

Publication Date

July 2012

Volume

108

Issue

3

Start / End Page

499 / 506

Location

United States

Related Subject Headings

  • Young Adult
  • Tissue Distribution
  • Thiazoles
  • Quinazolines
  • Pyrimidines
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Maximum Tolerated Dose