WEEKLY CONTINUOUS-INFUSION OF 5-FLUOROURACIL WITH ORAL LEUCOVORIN IN METASTATIC BREAST-CANCER PATIENTS WITH PRIMARY RESISTANCE TO DOXORUBICIN

Doxorubicin-resistant metastatic breast cancer (MBC) is a very poor pr ognosis scenario, where only taxanes have shown activity, often at the expense of severe toxicity that compromises palliation. This study wa s undertaken to test the antitumor activity and tolerability of infusi onal 5-fluorouracil (5-FU) modulated with low-dose oral leucovorin (LV ), in heavily pretreated patients with stringent criteria of primary r esistance to doxorubicin, visceral involvement, and suboptimal perform ance status. Twenty-six patients with measurable MBC and primary resis tance to anthracyclines received a weekly outpatient 48-hour infusion of high-dose 5-FU with low dose oral leucovorin. All patients were ass essable for response and toxicity. Eight partial responses were seen ( 30% response rate) in soft tissue and visceral sites, with a median re sponse duration of eight months (5 + to 12). 98% of the cycles were mi nimally toxic or non-toxic. Toxicities included mucositis, diarrhea, a nd plantar-palmar-syndrome. Our results suggest that this schedule of LV-modulated infusional 5-FU can produce a substantial number of long- lasting responses and meaningful palliation to this very poor prognosi s population.