Paclitaxel Plus Mitoxantrone for Poor-Prognosis Breast Cancer

LONDON—Combination 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 acceptable toxicity.

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.”