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.
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.
Siena
S
S
Divisione Oncologia Falck, Ospedale Niguarda Ca'Granda, Milan. Electronic address: salvatore.siena@ospedaleniguarda.it.
Crinò
L
L
Divisione Oncologia Medica, Policlinico Regionale Silvestrini, Perugia.
Danova
M
M
Divisione Oncologia Medica, Istituto Ricerca e Cura a Carattere Scientifico Policlinico San Matteo, Pavia.
Del Prete
S
S
Divisione Oncologia Medica, Ospedale San Giovanni di Dio, Frattamaggiore (Naples).
Cascinu
S
S
Clinica Oncologica Medica, Ospedali Riuniti Umberto I-Salesi, Torrette (Ancona).
Salvagni
S
S
Dipartimento Oncologia Medica, Ospedale di Parma, Parma.
Schiavetto
I
I
Divisione Oncologia Falck, Ospedale Niguarda Ca'Granda, Milan.
Vitali
M
M
Divisione Oncologia Medica B, Istituto Nazionale Tumori, Fondazione Istituto Ricerca e Cura a Carattere Scientifico, Milan, Italy.
Bajetta
E
E
Divisione Oncologia Medica B, Istituto Nazionale Tumori, Fondazione Istituto Ricerca e Cura a Carattere Scientifico, Milan, Italy.
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
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide