A phase II study of Imatinib for advanced adenoid cystic carcinoma of head and neck salivary glands

Pfeffer, M. Raphael; Talmi, Yoav P.; Catane, Raphael; Symon, Zvi; Yosepovitch, Ady; Levitt, Mark L.

doi:10.1016/j.oraloncology.2005.12.026

Cited by 161 publications

(87 citation statements)

References 17 publications

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“…We previously reported in the largest published study of single agent imatinib an SD rate of 60% (9/15) [16]. C-kit expression by immunohistochemistry (IHC) was not associated with SD in our study [16] and this has been confirmed in the correlative reports of two other phase II trials [21,22]. C-kit mutation status in these three trials is unknown but previous pathological series suggest that ACC is most often associated with wild type c-kit [9,10].…”

Section: Response and Survivalsupporting

confidence: 85%

“…Unfortunately in ACC, the targets are often unknown, imprecise or absent. For example, evidence of protein overexpression does not equate to evidence of activating mutations or 'oncogene addiction' as demonstrated by the absence of objective responses to imatinib in c-kit IHC-positive ACC tumors [16,22] and lapatinib in EGFR IHC-positive ACC tumors [26]. Increasing knowledge of ACC biology and promising in vivo preclinical studies will help inform future clinical trials [52][53][54].…”

Section: Implications For Future Clinical Trial Design In Advanced Accmentioning

confidence: 99%

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A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC

et al. 2012

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Background: Vascular endothelial growth factor (VEGF) and c-kit are highly expressed in adenoid cystic carcinoma (ACC) and associated with biologic aggressiveness. This study aimed to assess the antitumor activity of sunitinib, a multi-targeted inhibitor of vascular endothelial growth factor receptor, c-kit, platelet-derived growth factor receptor, ret proto-oncogene (RET) and FMS-like tyrosine kinase 3 (FLT3), in ACC of the salivary gland. Patients and methods:Patients with progressive, recurrent and/or metastatic ACC were treated with sunitinib 37.5 mg daily in this single-arm, two-stage phase II trial. Response was assessed every 8 weeks.Results: Fourteen patients were enrolled on to the study. Among 13 assessable patients, there were no objective responses, 11 patients had stable disease (SD), 8 patients had SD ‡6 months and 2 patients had progressive disease as best response. Median time to progression was 7.2 months. Median overall survival was 18.7 months. Toxic effects occurring in at least 50% of patients included fatigue, oral mucositis and hypophosphatemia usually of mild to moderate severity.Conclusions: Although no responses were observed, sunitinib was well tolerated, with prolonged tumor stabilization of ‡6 months in 62% of assessable patients. The lack of responses is comparable with other trials of molecularly targeted agents in ACC and highlights the need for novel strategies in phase II clinical trial design.

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Section: Response and Survivalsupporting

confidence: 85%

Section: Implications For Future Clinical Trial Design In Advanced Accmentioning

confidence: 99%

A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC

et al. 2012

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“…We agree with Moskaluk et al that published data from prospective clinical studies examining the role of anti-KIT-directed therapy have shown a very low response rate [9][10][11][12][13] and that therapeutic decisions should be made with caution. We recognize the limitations of our study, given our small sample size and lack of frozen-matched controls, which were not available for us to analyze at the time of this study.…”

supporting

confidence: 90%

Response to Moskaluk et al

et al. 2010

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“…However, in two separate phase II studies of adenoid cystic carcinoma, no objective responses were noted in a total of 30 patients (26 patients had confirmed KIT-positive tumors; refs. 39,40). In the current study, none of the 12 adenoid cystic carcinoma patients with confirmed expression of KIT had a CR or PR.…”

Section: Discussionmentioning

confidence: 44%

Phase II, Open-Label Study Evaluating the Activity of Imatinib in Treating Life-Threatening Malignancies Known to Be Associated with Imatinib-Sensitive Tyrosine Kinases

Heinrich

Joensuu

Demetri

et al. 2008

Clinical Cancer Research

192

139

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Purpose: To evaluate the activity of imatinib in treating advanced, life-threatening malignancies expressing one or more imatinib-sensitive tyrosine kinases. Experimental Design: This was a phase II, open-label, single arm study. Patients z15 years old with malignancies showing histologic or molecular evidence of expression/activation of imatinibsensitive tyrosine kinases were enrolled. Patients were treated with 400 or 800 mg/d imatinib for hematologic malignancy and solid tumors, respectively. Treatment was continued until disease progression or unacceptable toxicity. The primary objective was to identify evidence of imatinib activity with tumor response as the primary end point. Results: One hundred eighty-six patients with 40 different malignancies were enrolled (78.5% solid tumors, 21.5% hematologic malignancies). Confirmed response occurred in 8.9% of solid tumor patients (4 complete, 9 partial) and 27.5% of hematologic malignancy patients (8 complete, 3 partial). Notable activity of imatinib was observed in only five tumor types (aggressive fibromatosis, dermatofibrosarcoma protuberans, hypereosinophilic syndrome, myeloproliferative disorders, and systemic mastocytosis). A total of 106 tumors were screened for activating mutations: five KIT mutations and no platelet-derived growth factor receptor mutations were found. One patient with systemic mastocytosis and a partial response to therapy had a novel imatinibsensitive KIT mutation (D816T).There was no clear relationship between expression or activation of wild-type imatinib-sensitive tyrosine kinases and clinical response. Conclusion: Clinical benefit was largely confined to diseases with known genomic mechanisms of activation of imatinib target kinases. Our results indicate an important role for molecular characterization of tumors to identify patients likely to benefit from imatinib treatment.

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A phase II study of Imatinib for advanced adenoid cystic carcinoma of head and neck salivary glands

Cited by 161 publications

References 17 publications

A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC

A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC

Response to Moskaluk et al

Phase II, Open-Label Study Evaluating the Activity of Imatinib in Treating Life-Threatening Malignancies Known to Be Associated with Imatinib-Sensitive Tyrosine Kinases

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