Gebbia V, Borsellino N, Testa A, Tirrito M, Varvara F, Cucchiara A, Mauceri G, Girlando A, Ferrara M, Caruso F
Division of Medical Oncology, Centro Catanese di Oncologia, Catania, Italy.
Anticancer Res. 1999 Jul-Aug;19(4C):3553-7.
Effective palliation of metastatic breast carcinoma (MBC) after the failure of front-line chemotherapy for advanced disease, often based on the use of anthracyclines and taxanes, is quite difficult to achieve due to the development of dominant neoplastic cellular clones highly resistant to further therapy. Therefore the therapeutic index of second and third line chemotherapeutic treatments is usually quite low. Thirty patients with MBC with progressive disease after anthracycline-based chemotherapy as first line therapy were treated with l-FA 100 mg/m2/day and 5FU 1000 mg/m2/day ad continuous venous infusion for 96 hours every 4 weeks. Most patients (60%) had multiple sites of disease at entry and had visceral lesions as the dominant site of disease. Twenty-eight patients were evaluated for objective response: two patients had clinically progressive disease before restaging after the third cycle of chemotherapy. These patients were considered progressive disease since all patients were included in an intent-to-treat analysis. Nine patients achieved partial response for an overall response rate of 30% (intent-to-treat analysis) with a median duration of 9.5+ months (range 4.0/14.0 months), and disease stability was obtained in 10 cases (33%) with a median duration of 5.5 months (5-11). Progressive disease was recorded in 9 patients. After a median follow-up of 11 months, the overall median survival time of the whole series of patients was 14.0+ months. Objective responses were recorded both at visceral and bone sites. Chemotherapeutic treatment was generally quite well tolerated. No toxic deaths were recorded. Among gastrointestinal side-effects grade 3 stomatitis was noted in 30% of patients, and grade 3 diarrhea in 10% of cases. Grade 3-4 leukopenia was observed in 23% of patients, but significant episodes of febrile neutropenia were limited (2 patients). Grade 3 thrombocytopenia was seen only occasionally in 1 patient. Grade 1 anemia was recorded in 10% of patients. Hand-foot syndrome was noted in 2 patients (7%). Cardiotoxicity was minimal. The combination of 5FU and high-dose I-FA given as 96 hour continuous venous infusion was active, at least in terms of the overall response rate, against anthracycline refractory metastatic breast carcinoma. These results compare favourably with bolus 5FU/FA or other salvage regimens in terms of antineoplastic activity, and is well tolerated both subjectively and objectively by most patients.
转移性乳腺癌（MBC）在一线晚期疾病化疗失败后，由于出现对进一步治疗高度耐药的主要肿瘤细胞克隆，往往很难实现有效的姑息治疗。因此，二线和三线化疗的治疗指数通常很低。30例MBC患者在以蒽环类药物为一线治疗后病情进展，接受l - FA 100mg/m²/天和5FU 1000mg/m²/天持续静脉输注96小时，每4周一次。大多数患者（60%）在入组时有多个病灶部位，且以内脏病变为主要病灶部位。28例患者接受了客观反应评估：2例患者在化疗第三个周期后重新分期前临床病情进展。由于所有患者均纳入意向性分析，这些患者被视为病情进展。9例患者获得部分缓解，总缓解率为30%（意向性分析），中位缓解持续时间为9.5 +个月（范围4.0/14.0个月），10例患者病情稳定（33%），中位持续时间为5.5个月（5 - 11个月）。9例患者病情进展。在中位随访11个月后，整个系列患者的总体中位生存时间为14.0 +个月。在内脏和骨部位均记录到客观反应。化疗一般耐受性良好。未记录到毒性死亡病例。在胃肠道副作用方面，30%的患者出现3级口腔炎，10%的患者出现3级腹泻。23%的患者观察到3 - 4级白细胞减少，但严重的发热性中性粒细胞减少发作有限（2例患者）。仅1例患者偶尔出现3级血小板减少。10%的患者记录到1级贫血。2例患者（7%）出现手足综合征。心脏毒性极小。5FU和高剂量I - FA以96小时持续静脉输注联合使用，至少就总缓解率而言，对蒽环类药物难治性转移性乳腺癌有活性。就抗肿瘤活性而言，这些结果优于推注5FU/FA或其他挽救方案，并且大多数患者在主观和客观上耐受性良好。
