A phase II study of pemetrexed as second-line chemotherapy for the treatment of metastatic castrate-resistant prostate cancer (CRPC); Hoosier Oncology Group GU03-67.
BACKGROUND
No standard therapy exists for post-docetaxel castrate-resistant prostate cancer (CRPC) patients. This trial aimed to determine the safety and efficacy of pemetrexed in post-docetaxel CRPC patients.


METHODS
CRPC patients with progression after docetaxel (Taxotere) therapy received pemetrexed (500 mg/m2) i.v. every 3 weeks. The primary end point was prostate-specific antigen (PSA) response. A pharmacogenetic analysis of the reduced folate carrier-1 gene (RFC1) G80A polymorphism was also carried out.


RESULTS
Forty-nine patients were enrolled: median age 68 years, median baseline PSA 72 ng/ml, and median Karnofsky performance status of 90. Grade 3 or 4 toxicity occurred in 20 (43%) and four patients (8%), respectively. Confirmed >50% PSA decline occurred in four patients (8%), stable PSA lasting at least 12 weeks in 10 patients (20%). A significant relationship was observed between time from prior docetaxel therapy and overall survival. Pharmacogenetic analyses of RFC1 G80A genotype frequencies showed no relationship between genotypes and clinical efficacy.


CONCLUSIONS
Pemetrexed treatment of CRPC patients after docetaxel therapy was associated with only modest clinical activity. Further investigation of pemetrexed as a single agent in a nonenriched CRPC population is unlikely to add significant clinical benefit over that seen with traditional second-line chemotherapy agents such as mitoxantrone.
Hahn
N M
NM
Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
Zon
R T
RT
Yu
M
M
Ademuyiwa
F O
FO
Jones
T
T
Dugan
W
W
Whalen
C
C
Shanmugam
R
R
Skaar
T
T
Sweeney
C J
CJ
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005971:Glutamates / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D000068437:Pemetrexed; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
D000970:Antineoplastic Agents; D005971:Glutamates; D026901:Membrane Transport Proteins; C120043:SLC19A2 protein, human; D000068437:Pemetrexed; D006147:Guanine