Phase I study of weekly docetaxel and liposomal doxorubicin in patients with advanced solid tumors.
OBJECTIVE
To determine the maximum-tolerated doses (MTDs) and the dose-limiting toxicities (DLTs) of the weekly administration of docetaxel and pegylated liposomal doxorubicin (PEG-LD) in patients with advanced solid tumors.


METHODS
Forty-eight patients with solid tumors were enrolled in the study. Dose escalations of both drugs were given on a weekly basis for 3 consecutive weeks in cycles of 4 weeks. The starting dose for docetaxel was 20 mg/m(2)/week and for PEG-LD 6 mg/m(2)/week.


RESULTS
The MTD was 35 mg/m(2)/week for docetaxel and 14 mg/m(2)/week for PEG-LD. The DLTs at this level were grade 3 diarrhea (n=1 patient) and grade 3 mucositis (n=2 patients). There was no grade 4 hematologic or non-hematologic toxicity. Grade 3 neutropenia and thrombocytopenia occurred only in 1 and 2 patients, respectively. The non-hematologic toxicity was also mild with grade 2/3 fatigue in 8 patients, grade 2/3 neurotoxicity in 4, grade 2/3 mucositis in 8, grade 2/3 diarrhea in 4 and grade 2/3 nausea and vomiting in 5 patients. Two (5.7%) complete and 6 (17%) partial responses (overall response rate=22.7%; 95% confidence interval 9.6--32.4%) were observed among 35 evaluable patients. In 12 (63%) of 19 patients with hormone-refractory prostate cancer, a decline in serum levels of prostate-specific antigen of >50% was observed.


CONCLUSIONS
The weekly administration of docetaxel with PEG-LD is a well-tolerated regimen that merits further evaluation.
Kouroussis
Ch
Ch
First Department of Medical Oncology, 'Theagenion' Anticancer Hospital, Thessaloniki, Greece.
Androulakis
N
N
Vamvakas
L
L
Kalykaki
A
A
Spiridonakou
S
S
Kentepozidis
N
N
Saridaki
Z
Z
Xiropoulou
El
E
Georgoulias
V
V
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy; D011092:Polyethylene Glycols; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013274:Stomach Neoplasms / Q000188:drug therapy; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols; D004317:Doxorubicin