Phase II study of cisplatin and imatinib in advanced salivary adenoid cystic carcinoma

Ghosal, Niladri; Mais, Kathleen L; Shenjere, Patrick; Julyan, P. J.; Hastings, D. L.; Ward, Timothy H; Ryder, W. David J.; Bruce, Iain; Homer, Jarrod J; Slevin, Nicholas J

doi:10.1016/j.bjoms.2010.09.013

Cited by 65 publications

(43 citation statements)

References 22 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: 76%

“…Four phase II trials have evaluated imatinib in 75 patients with ACC (Table 4). Two partial responses have been reported in abstract form with single agent imatinib [23] and three partial responses have been reported with imatinib in combination with cisplatin [21]. We previously reported in the largest published study of single agent imatinib an SD rate of 60% (9/15) [16].…”

Section: Response and Survivalmentioning

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: 76%

Section: Response and Survivalmentioning

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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“…However, in 4 phase II clinical trials, only 2 of 42 patients with ACC treated with imatinib experienced objective tumor responses. The addition of cisplatin to imatinib also did not improve outcome as only 3 tumor responses were seen in 28 patients 67. These disappointing results suggest that the overexpressed c‐KIT receptors are not actively signaling in ACC cells or are not the major drivers of the malignant phenotype.…”

Section: Introductionmentioning

confidence: 97%

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

Chakraborty²,

et al. 2015

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BackgroundAdenoid cystic carcinoma (ACC) is a rare tumor of secretory glands. In this study, recent advances in molecular characterization and in therapeutics are reviewed.MethodsA search of articles in PubMed and of abstracts from national meetings was performed regarding ACC.ResultsRecent genetic analyses found that recurrent chromosome 6:9 translocations in ACC generate an MYB:NFIB gene fusion resulting in overexpression of the MYB oncoprotein. Several other frequent mutations are recently published that may be relevant for drug development. Several trials of targeted drugs are reviewed. Some agents delay tumor progression, but tumor responses remain rare.ConclusionACCs have a characteristic chromosomal translocation, but also frequently pick up additional mutations. Clinical research is limited by the rarity and slow growth of ACC. Several ongoing trials are testing agents that inhibit fibroblast growth factor receptor signaling or other signaling pathways. Novel treatments based on the recently sequenced tumor genome are under development. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. 38: 620–627, 2016

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“…C-kit overexpression is found in GIST, testicular seminoma, mast cell disease, melanoma, and acute myeloid leukemia 3 . The tyrosine kinase inhibitor against c-kit imatinib mesylate has demonstrated significant treatment response to chronic myelogenous leukemia and advanced c-kit-positive GIST 3 , and several studies demonstrated c-kit expression in the majority of ACC 18 . However, there are few previous studies of c-kit expression in MEC or CXPA.…”

Section: Discussionmentioning

confidence: 99%

“…In our study, similar to these previous reports, expression of c-kit in ACC was higher than in the other two histological subtypes, suggesting that the c-kit receptor could be specifically targeted in the treatment of patients with ACC. Ghosal et al 18 suggested that imatinib combined with cisplatin could reduce distant metastasis or local progression in ACC of the salivary gland. Mutations in the KIT gene could also affect the efficacy of such targeted therapies, although this remains a controversial issue for ACC and needs to be clarified in future studies.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Analysis of Various Salivary Gland Carcinomas Focusing on the Possibility of Molecular-targeted and Hormonal Therapy

Kawamura

Kunimura

Omatsu

et al. 2013

Showa Univ J Med Sci

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: This study aimed to determine the expression of c-kit, human epidermal growth factor receptor type 2 HER2 , insulin-like growth factor receptor IGFR , estrogen receptor ER , progesterone receptor PgR , vascular endothelial growth factor VEGF , c-MET, and survivin in adenoid cystic carcinomas ACC , carcinomas ex pleomorphic adenomas CXPA , and mucoepidermoid carcinomas MEC of the salivary glands. These expression levels and locations were compared to estimate the availability of molecular and hormonal targets for therapy in salivary gland carcinomas. Forty patients with a salivary gland carcinoma, diagnosed and treated at our hospital, were studied. On the basis of histopathology, 13, 12, and 15 patients were diagnosed with ACC, CXPA, and MEC, respectively. Associations between histological types were evaluated by Fisher s exact test, with a significance level of P 0.05. Compared with the other two histological types, ACC samples demonstrated significantly higher c-kit 85 , IGFR 77 , and ER 38 expression, while CXPA demonstrated significant HER2 75 staining, and MEC demonstrated significant IGFR 77 staining. The differences in expression of the tested markers among the histological types in our study suggested that c-kit-and IGFR-targeted therapy and anti-estrogen treatment could be effective in ACC, HER2-targeted therapy could be effective in CXPA, and that IGFR-target therapy could be effective in MEC of the salivary glands.

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Phase II study of cisplatin and imatinib in advanced salivary adenoid cystic carcinoma

Cited by 65 publications

References 22 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

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

Immunohistochemical Analysis of Various Salivary Gland Carcinomas Focusing on the Possibility of Molecular-targeted and Hormonal Therapy

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