Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies.
BACKGROUND
Pegylated liposomal doxorubicin (PEG-LD) and gemcitabine have single-agent activity in breast and ovarian carcinoma patients. We conducted a Phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in patients with advanced malignancies.


METHODS
Twenty-six patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of PEG-LD 20 mg/m(2) and gemcitabine 1000 mg/m(2) administered on Days 1 and 15 of a 28-day cycle.


RESULTS
The MTD was PEG-LD 20 mg/m(2) and gemcitabine 2000 mg/m(2) administered on Days 1 and 15 of a 28-day cycle. Dose-limiting toxicity, a Grade 3 rash, was observed in one patient during Cycle 1 and Grade 3 stomatitis and a rash were observed in a second patient during Cycle 2 after administration of PEG-LD 25 mg/m(2) and gemcitabine 2000 mg/m(2). Other side effects included palmar-plantar erythrodysesthesia, nausea, and fatigue. One complete and two partial responses were observed.


CONCLUSIONS
The recommended Phase II dose is PEG-LD 20 mg/m(2) with gemcitabine 2000 mg/m(2) on Days 1 and 15 of a 28-day cycle. A trial with this combination is currently ongoing at this institution comprising patients with refractory ovarian carcinoma.
Fracasso
Paula M
PM
Alvin J. Siteman Cancer Center, St. Louis, Missouri, USA. fracasso@im.wustl.edu
Blum
Kristie A
KA
Tan
Benjamin R
BR
Fears
Carole L
CL
Bartlett
Nancy L
NL
Arquette
Matthew A
MA
Clark
Romnee S
RS
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000209:etiology; D013280:Stomatitis / Q000209:etiology; D016896:Treatment Outcome; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D008081:Liposomes; D003841:Deoxycytidine; D004317:Doxorubicin; D000093542:Gemcitabine