Multicenter Phase II trial of high‐dose imatinib mesylate in metastatic melanoma

Wyman, Kenneth; Atkins, Michael B.; Prieto, Víctor M.; Eton, Omar; McDermott, David F.; Hubbard, Francie J.; Byrnes, Christine; Sanders, Kathleen; Sosman, Jeffrey A.

doi:10.1002/cncr.21834

Cited by 268 publications

(145 citation statements)

References 27 publications

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“…This was somewhat surprising, because imatinib at 800 mg/day has been reported to be associated with significant fluid retention and nausea [30,49,50]. We did observe nausea as a frequent toxicity, but it was not dose-limiting in the traditional sense.…”

Section: Discussionmentioning

confidence: 60%

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Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers

et al. 2015

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Background. Vascular endothelial growth factor and plateletderived growth factor signaling in the tumor microenvironment appear to cooperate in promoting tumor angiogenesis. Patients and Methods. We conducted a phase I trial combining bevacizumab (i.v. every 2 weeks) and imatinib (oral daily). Once a recommended phase II dose combination was established, a phase II trial was initiated in patients with metastatic melanoma. A Simon 2-stage design was used with 23 patients required in the first stage and 41 patients in total should the criteria to proceed be met. We required that 50% of the patients be progression-free at 16 weeks. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and power Doppler ultrasonography were performed in patients with metastatic tumors amenable to imaging with these methods at baseline and after 4 weeks. Results. A total of 17 patients were accrued to 4 dose and combination levels. Bevacizumab 10 mg/kg every 2 weeks

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Section: Discussionmentioning

confidence: 60%

“…Imatinib has been evaluated as a single-agent in two phase II trials in melanoma, neither of which was associated with significant clinical activity [29,30]. However, evidence in animal models suggests that the combination of VEGF and PDGF inhibition has significantly more antiangiogenic activity than blockade of either alone [31,32].…”

Section: Introductionmentioning

confidence: 99%

Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers

et al. 2015

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“…Furthermore, 3 phase 2 studies of metastatic melanoma treated with imatinib mesylate, an orally available ATPcompetitive inhibitor of several tyrosine kinases including KIT, did not demonstrate clinical activity [15,16]. These trials accrued before the discovery of activating mutations of KIT in melanoma and did not select patients based on the presence of KIT mutations or amplification.…”

Section: Discussionmentioning

confidence: 99%

Primary Melanoma of the Vagina Treated by Imatinib: Case Report

Oualla¹,

Elmrabet²,

Elfatemi³

et al. 2013

JCT

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Melanoma of the vagina is a rare lesion. It results from the malignant transformation of ectopic melanocytes occurring in post-menopause. The CKIT is expressed in 36% of cases in addition to melanoma markers. Prognosis is poor especially for inoperable and disseminated forms despite systemic therapy. Treatment with Imatinib is an option in cases of metastatic mucosal melanoma with CKIT mutation or amplification. We report the case of post-menopausal women, treated at Hassan II University Hospital, diagnosed with metastatic melanoma of the vagina, that didn't respond to first line of chemotherapy, and received Imatinib as second line of treatment, with good clinical response and durable stability at radiological assessment.

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“…Yet imatinib has been previously ruled out as a useful therapeutic agent, with significant reported toxicity but no effect [Wyman et al, 2006]. But here classification rears.…”

Section: Introductionmentioning

confidence: 87%

Causation and melanoma classification

Clarke

2010

Theor Med Bioeth

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While the clinical syndrome of melanoma was described during the nineteenth century, the pathology, aetiology and classification of the tumour remained controversial well into the twentieth. For instance, the debate about the type of tumour, its aetiology, classification and the relationship between pigmented moles and melanoma were common. This debate was widely regarded as settled by the 1960s, and we are now accustomed to think of melanoma as a single pathological and aetiological entity, with a number of possible clinical manifestations. A number of systems of classification are in common use. We may classify by site. So melanoma may occur on the skin (cutaneous), on the palms, soles and under the nails (acral) or on mucosal surfaces (mucosal). We may classify by tumour morphology -so tumours may be superficial spreading or nodular. Or we may classify by combinations of site and morphology.There are problems for these unificatory classifications, however. For instance, certain types of tumour (acral in particular) have widely varying incidence by race. A more significant challenge arises from recent research findings, especially the discovery that various genetic mutations (notably c-KIT and BRAF) seem to correlate with particular sub-types of melanoma. Their aetiological role is supported by the therapeutic success of agents directed against them. This suggests that the conventional systems of classification are in trouble, and much ongoing work is directed toward finding new ways of differentiating melanoma types with the intention of improving clinical outcomes, which will potentially require the clinical management of melanoma subtypes as distinct diseases.This raises exciting philosophical issues. For instance, what are the implications for systematic disease classification? Is there an optimum best single system for cases like these, or can we legitimately be more pluralistic, with possibly overlapping classificatory systems? How about the role of unification in this case? There is much debate to be found in the historical melanoma literature regarding the relative wisdom of either "lumping" and "splitting" as methodological approaches, with the repeated suggestion that strong forms of either strategies seemed likely to lead to difficulties.There is much to discuss here. However, I will focus on one area in particular -causation -with two aims. First, to outline the historical role of causation in the development of melanoma classification. Second, to suggest that, owing to the exploitable features of causal relationships, an attempt at a causal classification may be the optimal strategy in this case.

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Multicenter Phase II trial of high‐dose imatinib mesylate in metastatic melanoma

Cited by 268 publications

References 27 publications

Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers

Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers

Primary Melanoma of the Vagina Treated by Imatinib: Case Report

Causation and melanoma classification

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