title: First-line temozolomide combined with bevacizumab in metastatic melanoma: a multicentre phase II trial (SAKK 50/07).
abstract: BACKGROUND
  Oral temozolomide has shown similar efficacy to dacarbazine in phase III trials with median progression-free survival (PFS) of 2.1 months. Bevacizumab has an inhibitory effect on the proliferation of melanoma and sprouting endothelial cells. We evaluated the addition of bevacizumab to temozolomide to improve efficacy in stage IV melanoma.
  
  
  METHODS
  Previously untreated metastatic melanoma patients with Eastern Cooperative Oncology Group performance status of two or more were treated with temozolomide 150 mg/m(2) days 1-7 orally and bevacizumab 10 mg/kg body weight i.v. day 1 every 2 weeks until disease progression or unacceptable toxicity. The primary end point was disease stabilisation rate [complete response (CR), partial response (PR) or stable disease (SD)] at week 12 (DSR12); secondary end points were best overall response, PFS, overall survival (OS) and adverse events.
  
  
  RESULTS
  Sixty-two patients (median age 59 years) enrolled at nine Swiss centres. DSR12 was 52% (PR: 10 patients and SD: 22 patients). Confirmed overall response rate was 16.1% (CR: 1 patient and PR: 9 patients). Median PFS and OS were 4.2 and 9.6 months. OS (12.0 versus 9.2 months; P = 0.014) was higher in BRAF V600E wild-type patients.
  
  
  CONCLUSIONS
  The primary end point was surpassed showing promising activity of this bevacizumab/temozolomide combination with a favourable toxicity profile. Response and OS were significantly higher in BRAF wild-type patients.
authors.affiliation: Department of Medicine Oncology, Kantonal Hospital Graubuenden, Chur, Switzerland. roger.vonmoos@ksgr.ch
authors.forename: R
authors.initials: R
authors.lastname: von Moos
authors.forename: B
authors.initials: B
authors.lastname: Seifert
authors.forename: M
authors.initials: M
authors.lastname: Simcock
authors.forename: S M
authors.initials: SM
authors.lastname: Goldinger
authors.forename: S
authors.initials: S
authors.lastname: Gillessen
authors.forename: A
authors.initials: A
authors.lastname: Ochsenbein
authors.forename: O
authors.initials: O
authors.lastname: Michielin
authors.forename: R
authors.initials: R
authors.lastname: Cathomas
authors.forename: M
authors.initials: M
authors.lastname: Schläppi
authors.forename: H
authors.initials: H
authors.lastname: Moch
authors.forename: P H
authors.initials: PH
authors.lastname: Schraml
authors.forename: D
authors.initials: D
authors.lastname: Mjhic-Probst
authors.forename: C
authors.initials: C
authors.lastname: Mamot
authors.forename: N
authors.initials: N
authors.lastname: Schönewolf
authors.forename: R
authors.initials: R
authors.lastname: Dummer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000556:secondary; D000077204:Temozolomide
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide