Phase I study of prolonged-infusion gemcitabine combined with cyclophosphamide in patients with metastatic carcinoma of the breast: tolerability of an optimal dose schedule.
BACKGROUND
A phase I study was initiated to determine the maximum tolerated dose (MTD) of prolonged-infusion gemcitabine combined with cyclophosphamide in patients with metastatic breast carcinoma (MBC).


METHODS
Patients with MBC were treated with gemcitabine infusion at 10 mg/m2/min and cyclophosphamide by intravenous piggyback injection, 4 h after initiation of the infusion. We treated 3-6 patients at a particular dose level until the MTD was determined.


RESULTS
Overall, 44 patients received a total of 197 courses of therapy. Both drugs were given on days 1, 8 and 15 to 14 patients (68 courses). Delayed white blood cell recovery necessitated first protocol amendment to drop cyclophosphamide on days 8 and 15 in 9 patients (43 cycles). A second amendment was needed to drop gemcitabine on day 15 because of thrombocytopenia in 21 patients (86 courses). The dose-limiting toxicity was thrombocytopenia. The MTD of an optimal dose schedule was 800 mg/m2 gemcitabine infused at a rate of 10 mg/m2/min on days 1 and 8, and 400 mg/m2 cyclophosphamide, by intravenous piggyback injection, on day 1, 4 h after initiation of the gemcitabine infusion.


CONCLUSIONS
The MTD can be given safely every 4 weeks to patients with MBC. Phase II studies are warranted to evaluate the clinical activity of this therapy.
Estephan
Fadi
F
Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Tex., USA.
Valero
Vicente
V
Esteva
Francisco J
FJ
Mejia
Jaime A
JA
Frye
Debra K
DK
Ibrahim
Nuhad K
NK
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D003520:Cyclophosphamide; D000093542:Gemcitabine