LONDONCombination chemotherapy with paclitaxel (Taxol) and
mitoxantrone (Novantrone) represents a promising treatment strategy
for poor-prognosis breast cancer patients, investigators in a small
British study have concluded.
The combination led to major objective responses in 10 of 14 patients
who had relapsed early after initial therapy and who had widespread
involvement. The treatment was well tolerated and could be
administered on an outpatient basis.
Regimen Well Tolerated
The overall response rate with mitoxantrone and paclitaxel is
encouraging and shows that the regimen is effective in a poor-prognosis
patient population, Dr. Neville Davidson, an oncologist at
North Middlesex Hospital, London, said at the San Antonio Symposium.
The regimen was well tolerated; we observed no cardiotoxicity
and no treatment-related deaths.
Limited data exist on the combination of paclitaxel and mitoxantrone,
Dr. Davidson said. One small study of paclitaxel (135 mg/m²),
mitoxantrone (12 mg/m²), fluorouracil (350 mg/m²), and
leucovorin resulted in a 45% response rate (Proc ASCO 1995, abstract
64). Dr. Davidson and his colleagues sought to determine whether
increasing the dose of paclitaxel to 175 mg/m² in combination
with mitoxantrone would lead to an improved response rate with
The 14 patients had relapsed a median of 9 months after initial
therapy, and most had widespread disease involvement; 7 of the 14 had
bone metastases, 6 had liver metastases, and 2 had lung metastases.
Twelve of the patients had previously received adjuvant or
neoadjuvant chemotherapy, 10 had a history of adjuvant radiotherapy,
and 11 had been treated surgically. The women ranged in age from 37
to 66 years. All but one of the patients were postmenopausal.
The treatment regimen consisted of mitoxantrone 12 mg/m², and
paclitaxel 175 mg/m², repeated every 21days for a total of six
cycles. Assessment for response occurred just prior to the fourth
cycle of therapy, Dr. Davidson said.
At the initial assessment, six patients had a complete response, and
four had a partial response (71.5% overall response rate). All 10
responses persisted to the end of therapy. Median survival for the
entire cohort was 10.5 months and ranged between 2 and 17 months.
Grade 3-4 hematologic toxicity consisted of leukopenia in nine
patients and neutropenia in seven. Alopecia was the only severe
nonhematologic toxicity, occurring at grade 3 level of severity in
all 14 patients. Grade 1-2 peripheral neurotoxicity occurred in 13 of
14 patients; two-thirds of the patients had minor nausea and
vomiting; and six complained of fatigue.
No patient experienced cardiotoxicity, as assessed by clinical
examination, ECG, and echocardiography.
The patients received a total of 77 cycles of therapy. Ten of 14
patients required treatment modifications. Modifications consisted of
treatment delay in 5 cycles, dose reductions in 17 cycles, and dose
reduction and delay in 7 cycles.
The response rate with this combination was encouraging in this
poor-prognosis patient population, Dr. Davidson concluded.
The results warrant further clinical evaluation.