Phase II trial of pemetrexed as second-line therapy in patients with metastatic urothelial carcinoma.
OBJECTIVE
The purpose of this single-center phase II study was to determine the activity of pemetrexed administered as second-line therapy in patients with advanced urothelial carcinoma.


METHODS
Patients with advanced urothelial carcinoma that had relapsed after receiving perioperative chemotherapy, or progressed on first-line chemotherapy for metastatic disease, were eligible for enrollment. Patients received pemetrexed 500 mg/m(2) every 21 days along with folic acid and vitamin B12 supplementation.


RESULTS
A total of 13 patients were enrolled. An objective response was achieved in 1/12 evaluable patients for an overall response rate of 8% (90% upper limit 29%). This level of activity did not meet criteria for expansion based on the pre-defined optimal 2-stage Simon design and the trial was concluded. Treatment was generally well tolerated, however, 2/13 patients developed febrile neutropenia. Non-hematologic grade > or = 3 toxicity was rare.


CONCLUSIONS
Pemetrexed as second-line therapy in advanced urothelial carcinoma is associated with modest activity. The role of this novel antifolate in chemotherapy-naïve patients warrants further investigation.
Galsky
Matthew D
MD
Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Joan and Sanford Weill Medical College of Cornell University, New York, NY 10021, USA. mgalsky@hotmail.com
Mironov
Svetlana
S
Iasonos
Alexia
A
Scattergood
Joseph
J
Boyle
Mary G
MG
Bajorin
Dean F
DF
D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D004334:Drug Administration Schedule; D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D010386:Pelvic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000068437:Pemetrexed; D016879:Salvage Therapy; D016896:Treatment Outcome; D014523:Urethral Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000473:pathology*; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D014803:Vitamin B Complex; D006147:Guanine; D005492:Folic Acid; D014805:Vitamin B 12