title: Dose-dense temozolomide regimen for the treatment of brain metastases from melanoma, breast cancer, or lung cancer not amenable to surgery or radiosurgery: a multicenter phase II study.
abstract: BACKGROUND
  Brain metastases reduce survival because therapeutic options are limited. This phase II study evaluated the efficacy of single-agent therapy with alternating weekly, dose-dense temozolomide in pretreated patients with brain metastases prospectively stratified by primary tumor type.
  
  
  METHODS
  Eligible patients had bidimensionally measurable brain metastases from histologically/cytologically confirmed melanoma, breast cancer (BC), or non-small-cell lung cancer (NSCLC). Prior chemotherapy, radiotherapy, and whole-brain radiotherapy (WBRT) were allowed. Patients received temozolomide 150 mg/m(2)/day (days 1-7 and 15-21 every 28- or 35-day cycle).
  
  
  RESULTS
  In the intent-to-treat population (N = 157; 53 melanoma, 51 BC, and 53 NSCLC), one patient had complete response, nine (6%) had partial responses, and 31 (20%) had stable disease in the brain. Median progression-free survival was 56, 58, and 66 days for melanoma, BC, and NSCLC, respectively. Median overall survival was 100 days for melanoma, 172 days for NSCLC, and not evaluable in the BC group. Thrombocytopenia was the most common adverse event causing dose modification or treatment discontinuation. Grade 4 toxic effects were rare.
  
  
  CONCLUSIONS
  This alternating weekly, dose-dense temozolomide regimen was well tolerated and clinically active in heavily pretreated patients with brain metastases, particularly in patients with melanoma. Combining temozolomide with WBRT or other agents may improve clinical outcomes.
authors.affiliation: Divisione Oncologia Falck, Ospedale Niguarda Ca'Granda, Milan. Electronic address: salvatore.siena@ospedaleniguarda.it.
authors.forename: S
authors.initials: S
authors.lastname: Siena
authors.affiliation: Divisione Oncologia Medica, Policlinico Regionale Silvestrini, Perugia.
authors.forename: L
authors.initials: L
authors.lastname: Crinò
authors.affiliation: Divisione Oncologia Medica, Istituto Ricerca e Cura a Carattere Scientifico Policlinico San Matteo, Pavia.
authors.forename: M
authors.initials: M
authors.lastname: Danova
authors.affiliation: Divisione Oncologia Medica, Ospedale San Giovanni di Dio, Frattamaggiore (Naples).
authors.forename: S
authors.initials: S
authors.lastname: Del Prete
authors.affiliation: Clinica Oncologica Medica, Ospedali Riuniti Umberto I-Salesi, Torrette (Ancona).
authors.forename: S
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Dipartimento Oncologia Medica, Ospedale di Parma, Parma.
authors.forename: S
authors.initials: S
authors.lastname: Salvagni
authors.affiliation: Divisione Oncologia Falck, Ospedale Niguarda Ca'Granda, Milan.
authors.forename: I
authors.initials: I
authors.lastname: Schiavetto
authors.affiliation: Divisione Oncologia Medica B, Istituto Nazionale Tumori, Fondazione Istituto Ricerca e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Vitali
authors.affiliation: Divisione Oncologia Medica B, Istituto Nazionale Tumori, Fondazione Istituto Ricerca e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bajetta
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology* / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000628:therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000628:therapy; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D010166:Palliative Care; D011446:Prospective Studies; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide