Phase II study of a cremophor-free, polymeric micelle formulation of paclitaxel for patients with advanced urothelial cancer previously treated with gemcitabine and platinum.
BACKGROUND
Genexol-PM is a novel Cremophor® EL (CrEL)-free polymeric micelle formulation of paclitaxel. This multicenter phase II study was designed to evaluate the efficacy and safety of Genexol-PM monotherapy in patients with advanced urothelial carcinoma who developed disease progression after gemcitabine and cisplatin combination chemotherapy.


METHODS
Patients received Genexol-PM 240 mg/m(2) intravenously over 3 h every 3 weeks without premedication. Intra-patient dose escalation to 300 mg/m(2) was allowed during the second and subsequent cycles if pre-specified toxicities were not observed during the first cycle. The primary endpoint was response.


RESULTS
Thirty-seven patients were enrolled in this study. Platinum-free interval was less than 6 months in 27 (73%) patients, and 24 (64%) were categorized as having intermediate or poor prognosis according to Bajorin's criteria. Of 34 evaluable patients, there were 7 responses (21%; 95% CI, 7-34%), including one complete response (CR), with a median response duration of 6.5 months (95% CI, 3.5-9.6 months). The median time to progression was 2.7 months (95% CI, 0.9-4.6 months) with a median overall survival of 6.5 months (95% CI, 5.0-8.0 months). The most common grade 3/4 non-hematologic toxicities were peripheral neuropathy (sensory type 5.9%; motor type 8.8%) and infection (5.9%). Grade ≥3 hematologic toxicities occurred in only one patient.


CONCLUSIONS
Genexol-PM was generally well tolerated and demonstrated sufficient antitumor activity to warrant further development when used as second-line chemotherapy after gemcitabine-cisplatin failure in patients with urothelial carcinoma (NCT01426126).
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 138-736, Korea.
Jae-Lyun
JL
Lee
Jin-Hee
JH
Ahn
Se Hoon
SH
Park
Ho Young
HY
Lim
Jung Hye
JH
Kwon
Shin
S
Ahn
Cheryn
C
Song
Jun Hyuk
JH
Hong
Choung-Soo
CS
Kim
Hanjong
H
Ahn
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008823:Micelles; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D011379:Prognosis; D014571:Urologic Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D009944:Organoplatinum Compounds; D011108:Polymers; D003841:Deoxycytidine; C022131:cremophor; D011092:Polyethylene Glycols; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine