Phase II trial of neoadjuvant temozolomide in resectable melanoma patients.
BACKGROUND
We treated melanoma patients with temozolomide (TMZ) in the neoadjuvant setting and collected cryopreserved tumor samples before and after treatment. The primary objective was to determine whether the response proportion was higher than previously reported in widely metastatic patients. A secondary objective was to test the feasibility of obtaining adequate tissue before and after treatment for genetic testing.


METHODS
Chemotherapy-naive melanoma patients who were candidates for surgical resection were eligible. TMZ was administered orally at 75 mg/m(2)/day for 6 weeks of every 8-week cycle. Cycles were repeated until complete response (CR), progression, or stable disease (SD) for two cycles.


RESULTS
Of 19 assessable patients, 2 had CRs and 1 had partial response. Four patients had SD; 12 progressed. Tumor O-6-methylguanine-DNA methyltransferase (MGMT) promoter was unmethylated in all nine patients analyzed including from the two CR patients. Pretreatment tumor microarray results were obtained in 16 of 19 patients.


CONCLUSIONS
The response proportion to TMZ in the neoadjuvant setting was 16%, not different than in the metastatic setting. Responses were seen even in tumors with a methylated MGMT promoter. Pretreatment cryopreserved tumor adequate for microarray analysis could be obtained in most, but not all, patients. Post-treatment tumor was unavailable in complete responders.
Shah
G D
GD
Department of Medicine.
Socci
N D
ND
Department of The Computational Biology Center.
Gold
J S
JS
Department of Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Wolchok
J D
JD
Department of Medicine.
Carvajal
R D
RD
Department of Medicine.
Panageas
K S
KS
Department of Epidemiology and Biostatistics.
Viale
A
A
Department of The Genomics Core Laboratory.
Brady
M S
MS
Department of Surgery.
Coit
D G
DG
Department of Surgery.
Chapman
P B
PB
Department of Medicine. Electronic address: chapmanp@mskcc.org.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics
D000970:Antineoplastic Agents; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide