Phase I study of stealth liposomal doxorubicin in combination with gemcitabine in the treatment of patients with metastatic breast cancer.
OBJECTIVE
We conducted a single-institution phase I clinical trial to determine the maximum-tolerated dose (MTD) and define the toxic effects of stealth liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer.


METHODS
Patients were eligible if they had disease progression with no limit on prior number of chemotherapy regimens. Prior treatment with liposomal doxorubicin and/or gemcitabine was not allowed. The starting dose of liposomal doxorubicin was 20 mg/m(2) on day 1 only with a 20% dose escalation of the previous mg/m(2) dose until MTD was reached. Gemcitabine was given as a fixed dose of 800 mg/m(2) on days 1 and 8 every 3 weeks.


RESULTS
We treated 27 patients of whom six had never received chemotherapy for their disease. Most had had visceral involvement as their dominant site of disease. The dose-limiting toxicity was myelosuppression, which included neutropenia and thrombocytopenia. However, neither neutropenic fever nor episodes of bleeding were major occurrences. Significant antitumor activity was also observed with a total of two complete and seven partial responses. The recommended phase II dose is liposomal doxorubicin 24 mg/m(2) on day 1 and gemcitabine 800 mg/m(2) on days 1 and 8 every 21 days.


CONCLUSIONS
The combination of liposomal doxorubicin and gemcitabine is an active and well tolerated regimen when administered on a 21-day schedule. Myelosuppression limited further dose escalation, however, it did not increase the incidence of neutropenic fever. Significant antitumor activity seen in heavily and minimally pretreated patients warrants further evaluation of this combination.
Rivera
E
E
Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. erivera@notes.mdacc.tmc.edu
Valero
V
V
Syrewicz
L
L
Rahman
Z
Z
Esteva
F J
FJ
Theriault
R L
RL
Rosales
M M
MM
Booser
D
D
Murray
J L
JL
Bast
R C
RC
Hortobagyi
G N
GN
Esteva
F L
FL
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D008081:Liposomes; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D000093542:Gemcitabine
D008081:Liposomes; D003841:Deoxycytidine; D004317:Doxorubicin; D000093542:Gemcitabine