title: 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.
abstract: OBJECTIVE
  To determine the tolerability and efficacy of daily oral marimastat (BB-2516 in patients with metastatic melanoma and to determine the matrix metalloproteinase (MMP) activity, tumour necrosis, peri- and intra-tumoral fibrosis and tumor inflammation in pre- and post-treatment tumor biopsies.
  
  
  METHODS
  Patients with measurable metastatic melanoma who had received no more than one prior chemotherapy regimen and lesions accessible for biopsy were eligible. The first 18 were treated with 100 mg p.o. twice daily and the next 11 received a reduced dose of 10 mg p.o. twice daily because of musculoskeletal toxicity. Response was assessed according to standard criteria.
  
  
  RESULTS
  Twenty-nine patients were entered and 28 were eligible. Five had early progression (< 4 weeks of therapy), 2 experienced a partial responses persisting for 3.2 months and 3.6 months, 5 had stable disease and 16 progressive disease. Eleven patients had both pre- and post-treatment biopsies. In 3, no tumor tissue was present in one or the other biopsy. Two patients showed a clear increase in peri-tumoral fibrosis and two others showed an increase in tumor necrosis, but no consistent pattern in histologic changes was seen. In one patient, who later developed a PR, apoptosis was increased.
  
  
  CONCLUSIONS
  Marimastat has only limited activity in patients with metastatic malignant melanoma. However, the observation of two partial responses was interesting given that this agent might have been expected to cause tumor stasis rather than regression. Additional studies will be required to determine if the development of peri-tumoral fibrosis or tumor necrosis antedates a clinical response to marimastat.
authors.affiliation: Department of Medical Oncology & Hematology, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Canada. ian.quirt@uhn.on.ca
authors.forename: Ian
authors.initials: I
authors.lastname: Quirt
authors.forename: Audley
authors.initials: A
authors.lastname: Bodurth
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lohmann
authors.forename: James
authors.initials: J
authors.lastname: Rusthoven
authors.forename: Karl
authors.initials: K
authors.lastname: Belanger
authors.forename: Vincent
authors.initials: V
authors.lastname: Young
authors.forename: Nancy
authors.initials: N
authors.lastname: Wainman
authors.forename: William
authors.initials: W
authors.lastname: Stewar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Eisenhauer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024221:Antineoplastic Protocols; D001706:Biopsy; D002170:Canada; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D008875:Middle Aged
chemical_list: D006877:Hydroxamic Acids; C100342:marimastat; D008666:Metalloendopeptidases