Phase I dose and sequencing study of pegylated liposomal doxorubicin and docetaxel in patients with advanced malignancies.
BACKGROUND
Pegylated liposomal doxorubicin (PEG-LD) and docetaxel have single-agent activity in several malignancies. The authors conducted a Phase I trial to evaluate the maximum tolerated dose (MTD), toxicities, and effect of dose sequencing of this combination in patients with advanced malignancies.


METHODS
Twenty-two patients were enrolled in this two-arm, accelerated, dose escalation trial. Both drugs were administered on Days 1 and 15 of a 28 day cycle. In Arm A, dose escalation proceeded from a sequence and starting dose of 15 mg/m(2) PEG-LD and 30 mg/m(2) docetaxel. In Arm B, dose escalation proceeded from a sequence and starting dose of 30 mg/m(2) docetaxel and 15 mg/m(2)PEG-LD. In both arms, the dose of each drug was increased alternately by 5 mg/m(2) at each dose level.


RESULTS
The MTD for Arm A was 20 mg/m(2) PEG-LD and 40 mg/m(2) docetaxel, both of which were administered on Days 1 and 15 of a 28-day cycle. The MTD for Arm B was 35 mg/m(2) docetaxel and 20 mg/m(2) PEG-LD, both of which were administered on Days 1 and 15 of a 28-day cycle. Dose-limiting toxicities were Grade 3 (according to the National Cancer Institute Common Toxicity Criteria) skin toxicity and thrombocytopenia. One partial response was observed and stable disease was documented for three patients.


CONCLUSIONS
The recommended sequence and dose is 20 mg/m(2) PEG-LD followed by 40 mg/m(2) docetaxel on Days 1 and 15 of a 28-day cycle in Phase II trials for patients with breast and ovarian carcinoma to establish the efficacy of this well tolerated regimen.
Fracasso
Paula M
PM
Alvin J. Siteman Cancer Center, St. Louis, Missouri 63110, USA. francasso@im.wustl.edu
Rodriguez
Luis C
LC
Herzog
Thomas J
TJ
Fears
Carole L
CL
Goodner
Sherry A
SA
Govindan
Ramaswamy
R
Picus
Joel
J
Rader
Janet S
JS
Tan
Benjamin R
BR
Arquette
Matthew A
MA
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008081:Liposomes; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D043823:Taxoids; D016896:Treatment Outcome
D008081:Liposomes; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols; D004317:Doxorubicin; D017239:Paclitaxel