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Phase II evaluation of imatinib mesylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group Study.
J Clin Oncol. 2008 Jul 10; 26(20):3418-25.JC

Abstract

PURPOSE

This phase II trial assessed the activity and tolerability of an oral dose of imatinib mesylate 400 mg twice daily in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma. The association between the expression of certain markers and clinical outcome was investigated.

PATIENTS AND METHODS

Primary measure of clinical efficacy was progression-free survival (PFS) at 6 months. Mutational analysis of KIT, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay for markers (KIT, platelet-derived growth factor [PDGF] receptor [-R], AKT2, phosphorylated AKT [p-AKT], stem cell factor [SCF], and PDGF) were performed.

RESULTS

Fifty-six eligible patients were evaluated. Nine patients were progression free for at least 6 months including one complete responder. The median PFS and survival were 2 and 16 months, respectively. The most common grade 3 and 4 toxicities were neutropenia, GI, dermatologic effects, pain, and electrolyte disturbances. At least one target of imatinib (KIT, PDGFR-alpha, or PDGFR-beta) was expressed in all tumors, and most tumors expressed all three receptors. Higher expression of p-AKT and PDGFR-beta were associated with shorter PFS, and higher IHC scores (% immunopositive cells x staining intensity) of SCF and p-AKT were associated with decreased overall survival. No sequence mutations were detected in the KIT gene. Higher pretreatment plasma concentrations of PDGF-AB, PDGF-BB, and vascular endothelial growth factor (VEGF) were individually associated with shorter PFS and survival.

CONCLUSION

Imatinib mesylate was well tolerated but had minimal single-agent activity in patients with recurrent ovarian or primary peritoneal carcinoma. No marker was identified that would predict activity of imatinib; however, tumor p-AKT and plasma VEGF levels were associated with poor outcome.

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Authors+Show Affiliations

Schilder RJ
Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA. russell.schilder@fccc.edu
Sill MW
No affiliation info available
Lee RB
No affiliation info available
Shaw TJ
No affiliation info available
Senterman MK
No affiliation info available
Klein-Szanto AJ
No affiliation info available
Miner Z
No affiliation info available
Vanderhyden BC
No affiliation info available

MeSH

AdultAgedAged, 80 and overBenzamidesBiomarkers, TumorDNA Mutational AnalysisDisease-Free SurvivalDose-Response Relationship, DrugDrug Administration ScheduleEnzyme-Linked Immunosorbent AssayFemaleFollow-Up StudiesHumansImatinib MesylateImmunohistochemistryKaplan-Meier EstimateMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingNeoplasms, Glandular and EpithelialOvarian NeoplasmsPeritoneal NeoplasmsPiperazinesProbabilityPyrimidinesRisk AssessmentSurvival AnalysisTreatment Outcome

Pub Type(s)

Clinical Trial, Phase II
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18612157

Citation

Schilder, Russell J., et al. "Phase II Evaluation of Imatinib Mesylate in the Treatment of Recurrent or Persistent Epithelial Ovarian or Primary Peritoneal Carcinoma: a Gynecologic Oncology Group Study." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 26, no. 20, 2008, pp. 3418-25.
Schilder RJ, Sill MW, Lee RB, et al. Phase II evaluation of imatinib mesylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2008;26(20):3418-25.
Schilder, R. J., Sill, M. W., Lee, R. B., Shaw, T. J., Senterman, M. K., Klein-Szanto, A. J., Miner, Z., & Vanderhyden, B. C. (2008). Phase II evaluation of imatinib mesylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group Study. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 26(20), 3418-25. https://doi.org/10.1200/JCO.2007.14.3420
Schilder RJ, et al. Phase II Evaluation of Imatinib Mesylate in the Treatment of Recurrent or Persistent Epithelial Ovarian or Primary Peritoneal Carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2008 Jul 10;26(20):3418-25. PubMed PMID: 18612157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phase II evaluation of imatinib mesylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group Study. AU - Schilder,Russell J, AU - Sill,Michael W, AU - Lee,Roger B, AU - Shaw,Tanya J, AU - Senterman,Mary K, AU - Klein-Szanto,Andres J, AU - Miner,Zoe, AU - Vanderhyden,Barbara C, PY - 2008/7/10/pubmed PY - 2008/8/14/medline PY - 2008/7/10/entrez SP - 3418 EP - 25 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J Clin Oncol VL - 26 IS - 20 N2 - PURPOSE: This phase II trial assessed the activity and tolerability of an oral dose of imatinib mesylate 400 mg twice daily in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma. The association between the expression of certain markers and clinical outcome was investigated. PATIENTS AND METHODS: Primary measure of clinical efficacy was progression-free survival (PFS) at 6 months. Mutational analysis of KIT, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay for markers (KIT, platelet-derived growth factor [PDGF] receptor [-R], AKT2, phosphorylated AKT [p-AKT], stem cell factor [SCF], and PDGF) were performed. RESULTS: Fifty-six eligible patients were evaluated. Nine patients were progression free for at least 6 months including one complete responder. The median PFS and survival were 2 and 16 months, respectively. The most common grade 3 and 4 toxicities were neutropenia, GI, dermatologic effects, pain, and electrolyte disturbances. At least one target of imatinib (KIT, PDGFR-alpha, or PDGFR-beta) was expressed in all tumors, and most tumors expressed all three receptors. Higher expression of p-AKT and PDGFR-beta were associated with shorter PFS, and higher IHC scores (% immunopositive cells x staining intensity) of SCF and p-AKT were associated with decreased overall survival. No sequence mutations were detected in the KIT gene. Higher pretreatment plasma concentrations of PDGF-AB, PDGF-BB, and vascular endothelial growth factor (VEGF) were individually associated with shorter PFS and survival. CONCLUSION: Imatinib mesylate was well tolerated but had minimal single-agent activity in patients with recurrent ovarian or primary peritoneal carcinoma. No marker was identified that would predict activity of imatinib; however, tumor p-AKT and plasma VEGF levels were associated with poor outcome. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/18612157/Phase_II_evaluation_of_imatinib_mesylate_in_the_treatment_of_recurrent_or_persistent_epithelial_ovarian_or_primary_peritoneal_carcinoma:_a_Gynecologic_Oncology_Group_Study_ L2 - https://ascopubs.org/doi/10.1200/JCO.2007.14.3420?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -