Primary chemotherapy with gemcitabine as prolonged infusion, non-pegylated liposomal doxorubicin and docetaxel in patients with early breast cancer: final results of a phase II trial.
BACKGROUND
Combinations of anthracyclines, taxanes and gemcitabine have shown high activity in breast cancer. This trial was designed to evaluate a modified combination regimen as primary chemotherapy. Non-pegylated liposomal doxorubicin (NPLD) was used instead of conventional doxorubicin to improve cardiac safety. Gemcitabine was given 72 h after NPLD and docetaxel as a prolonged infusion over 4 h in order to optimize synergistic effects and accumulation of active metabolites.


METHODS
Forty-four patients with histologically confirmed stage II or III breast cancer were treated with NPLD (60 mg/m(2)) and docetaxel (75 mg/m(2)) on day 1 and gemcitabine as 4-h infusion (350 mg/m(2)) on day 4. Treatment was repeated every 3 weeks for a maximum of six cycles. All patients received prophylactically recombinant granulocyte colony-stimulating factor. Patients with axillary lymph node involvement after primary chemotherapy received adjuvant treatment with cyclophosphamide, methotrexate and fluorouracil.


RESULTS
The clinical response rate was 80%, and complete remissions of the primary tumor occurred in 10 patients (25%). Breast conservation surgery was performed in 19 out of 20 patients (95%) with an initial tumor size of less than 3 cm and in 14 patients (70%) with a tumor size <or=3 cm. Seven patients had histologically confirmed complete responses accounting for a pCR rate of 17.5%. Expression of Ki--67 was the most important predictive parameter for response with high 38.9% breast pCR rate in patients with elevated Ki--67 expression. Although the predominant toxicity was myelosuppression with grade 3/4 neutropenia in 61% of patients few neutropenic complications resulted. Non-hematological toxicity was generally moderate with grade 3 or 4 toxicity in 10.0% of cycles. Most common non-hematologic toxicities were nausea, vomiting, alopecia, mucositis, asthenia and elevation of liver enzymes.


CONCLUSIONS
The evaluated schedule provides a safe and highly effective combination treatment for patients with early breast cancer, which is suitable for phase III studies.
Schmid
P
P
Medizinische Klinik mit Schwerpunkt Onkologie und Hämatologie, Charité Campus Mitte, Humboldt Universität zu Berlin, Berlin. peter.schmid@charite.de
Krocker
J
J
Jehn
C
C
Michniewicz
K
K
Lehenbauer-Dehm
S
S
Eggemann
H
H
Heilmann
V
V
Kümmel
S
S
Schulz
C O
CO
Dieing
A
A
Wischnewsky
M B
MB
Hauptmann
S
S
Elling
D
D
Possinger
K
K
Flath
B
B
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D015412:Mastectomy, Segmental; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
D008081:Liposomes; D043823:Taxoids; D003841:Deoxycytidine; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D004317:Doxorubicin; D000093542:Gemcitabine