Abstract
Objectives: To determine thetolerability and efficacy of daily oralmarimastat (BB-2516 in patients withmetastatic melanoma and to determine thematrix metalloproteinase (MMP) activity,tumour necrosis, peri- and intra-tumoralfibrosis and tumor inflammation in pre- and post-treatmenttumor biopsies.
Patients and methods: Patients withmeasurable metastatic melanoma who hadreceived no more than one priorchemotherapy regimen and lesions accessiblefor biopsy were eligible. The first 18 weretreated with 100 mg p.o. twice daily and thenext 11 received a reduced dose of 10 mgp.o. twice daily because of musculoskeletaltoxicity. Response was assessed accordingto standard criteria.
Results: Twenty-nine patients were entered and 28 wereeligible. Five had early progression (< 4 weeks oftherapy), 2 experienced a partial responsespersisting for 3.2 months and 3.6 months, 5had stable disease and 16 progressivedisease. Eleven patients had both pre- andpost-treatment biopsies. In 3, no tumortissue was present in one or the otherbiopsy. Two patients showed a clearincrease in peri-tumoral fibrosis and twoothers showed an increase in tumornecrosis, but no consistent pattern inhistologic changes was seen. In onepatient, who later developed a PR,apoptosis was increased.
Conclusion: Marimastat has onlylimited activity in patients withmetastatic malignant melanoma. However,the observation of two partial responseswas interesting given that this agent mighthave been expected to cause tumor stasisrather than regression. Additional studieswill be required to determine if thedevelopment of peri-tumoral fibrosis ortumor necrosis antedates a clinicalresponse to marimastat.
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Quirt, I., Bodurtha, A., Lohmann, R. et al. Phase II Study of Marimastat (BB-2516) in Malignant Melanoma – A Clinical and Tumor Biopsy Study of the National Cancer Institute of Canada Clinical Trials Group. Invest New Drugs 20, 431–437 (2002). https://doi.org/10.1023/A:1020625423524
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DOI: https://doi.org/10.1023/A:1020625423524