Vinorelbine, cisplatin and continuous infusion of 5-fluorouracil (ViFuP) in metastatic breast cancer patients: a phase II study.
OBJECTIVE
Chemotherapy regimens for patients with advanced breast cancer or large primary tumours (including locally advanced disease) usually contain anthracyclines, taxanes or both. We investigated a multi-agent regimen for patients for whom anthracyclines and/or taxanes may not be suitable. We assessed efficacy in terms of response rate and time to progression of a combination with continuous infusion 5-fluorouracil (5-FU), vinorelbine and cisplatin (ViFuP regimen), as a first or subsequent line treatment for metastatic breast cancer patients.


METHODS
One hundred consecutive patients with advanced breast cancer were treated with 5-FU 200 mg/m2 administered continuously through a permanent central venous line; vinorelbine was given on days 1 and 3 at a dose of 20 mg and cisplatin was administered at 60 mg/m2 on day one. Therapy was given every three weeks. The median age was 50 years (range 23-72). Fifty-two patients had received prior chemotherapy for metastatic breast cancer, and sixty-one percent had previously received anthracyclines, thirty-five percent taxanes and twenty-nine percent 5-FU as a bolus injection. All patients were assessable for toxicity, four patients were not assessable for response.


RESULTS
There were four complete responses (4%). Forty-nine patients had a partial response (overall response rate, 55%; 95% confidence interval (CI): 45%-65%). After a median follow-up of 10.2 months, median duration of response is 5.2 months (range 1.5-20.7+ months), time to progression (TTP) is 6.8 months (range 0.3-24.7 months). Acute toxicity, including myelosuppression, was mild: only 18% of patients had grade 4 granulocytopenia and one patient experienced grade 4 diarrhea. Only 15% of patients had any non-hematological grade 3 toxicity including nausea (4%), stomatitis (4%), diarrhea (2%), fatigue (1%), fever (1%), photosensitivity (1%), hand-foot syndrome (1%). Grade 2 alopecia was observed only in six patients (6%). Eleven patients developed a right diaphragmatic supra elevation, while deep vein thrombosis, central venous catheter associated, occurred in eight patients.


CONCLUSIONS
We identified a combination chemotherapy with noteworthy efficacy and well tolerated subjectively as either a first- or second-line treatment for metastatic breast cancer patients. The regimen warrants further development focusing on the comparison with either continuous administration of oral fluoropyrimidine derivatives.
Nolè
F
F
Division of Medical Oncology, European Institute of Oncology, Milan, Italy. franco.nole@ieo.it
Munzone
E
E
Mandalà
M
M
Catania
C
C
Orlando
L
L
Zampino
M G
MG
Minchella
I
I
Colleoni
M
M
Peruzzotti
G
G
Marrocco
E
E
Goldhirsch
A
A
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; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives
D014747:Vinblastine; D002945:Cisplatin; D005472:Fluorouracil