Phase I study of fixed dose gemcitabine plus epirubicin in patients with advanced solid malignancies.
OBJECTIVE
A Phase I study was initiated to investigate fixed dose rate gemcitabine (GEM) combined with epirubicin (EPI) given weekly or every other week, since, GEM given as a standard 30 minute infusion has modest activity. The study was designed based on the hypothesis that prolonged exposure (over 90 minutes) may improve response rates and combination with epirubicin (EPI) is synergistic.


METHODS
Eligible patients had measurable refractory solid malignancies with adequate bone marrow, renal, and liver functions. Patients received GEM 800, 1000, 1250 mg/m(2) over 90 minutes followed by EPI 10 or 15 mg/m(2) as a 30 minutes infusion on days 1, 8, and 15 or days 1 and 15 of a 28 day cycle.


RESULTS
Twenty-eight patients were enrolled and 24 are evaluable for overall toxicities and response rate. Toxicities include neutropenia (Gr 3 of Gr 4, 9 pts), thrombocytopenia (Gr 3 of Gr 4, 3 pts), fatigue (Gr 3 of Gr 4, 4 pts), and myalgia (Gr 3 of Gr 4, 1 pt). Dose limiting toxicity was grade 4 neutropenia. Seven patients experienced stable disease for >16 weeks and 3 patients with pancreatic cancer had partial responses.


CONCLUSIONS
The maximum tolerated dose is GEM 800 mg/m(2)/EPI 10 mg/m(2) days 1, 8, 15 or GEM 1000 mg/m(2)/EPI 15 mg/m(2) days 1, 15 given every 4 weeks. Further studies are warranted with targeted therapies to define the efficacy of this doublet.
Mahadevan
Daruka
D
Arizona Cancer Center, University of Arizona Health Sciences Center, Tucson, Arizona, USA. dmahadevan@azcc.arizona.edu
Dreisbach
Luke
L
Kristedja
Timothy
T
Williams
Debbie
D
Obregon
Yrma
Y
Kurtin
Sandy
S
Von Hoff
Daniel D
DD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D015251:Epirubicin; D000093542:Gemcitabine