McLaughlin P, Hagemeister F B, Romaguera J E, Sarris A H, Pate O, Younes A, Swan F, Keating M, Cabanillas F
Department of Hematology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
J Clin Oncol. 1996 Apr;14(4):1262-8. doi: 10.1200/JCO.1996.14.4.1262.
Although most patients with indolent lymphomas respond to initial therapy, virtually all experience relapse. Secondary therapy is often beneficial, but responses are rarely, if ever, durable. We conducted this phase II trail to evaluate the therapeutic efficacy and toxicity of fludarabine, mitoxantrone, and dexamethasone (FND) in patients with relapsed indolent lymphoma.
Fifty-one patients with recurrent or refractory indolent lymphoma were treated with a regimen of fludarabine 25 mg/m2/d intravenously (IV) on days 1 to 3, mitoxantrone 10 mg/m2 IV on day 1, and dexamethasone 20 mg/d IV or orally on days 1 to 5. Treatment was repeated at 4-week intervals for a maximum of eight courses. Late in the course of this trial, trimethoprim-sulfamethoxazole (TMP-SMX) was incorporated for Pneumocystis carinii (PCP) prophylaxis.
Responses were complete (CR) in 24 patients (47%) and partial (PR) in 24 (47%). The median failure-free survival time was 21 months for CR patients and 9 months for PR patients. Notable activity of FND was seen even in the elderly, in those with high serum lactate dehydrogenase (LDH) or beta2-microglobulin levels, and in those with multiple prior treatment regimens. The predominant toxic effects were myelosuppression and infections; other toxic effects were modest. Infections occurred in 12% of courses. Almost half of the infections were proven or suspected opportunistic infections, including six cases of dermatomal herpes zoster and two cases of proven PCP pneumonia.
The FND combination is highly active in patients with recurrent or relapsed indolent lymphoma and results in a high percentage of CRs. Because of the risk of opportunistic infections, we currently recommend prophylaxis with TMP-SMX and advise deletion of corticosteroids for patients who develop opportunistic infections.
尽管大多数惰性淋巴瘤患者对初始治疗有反应，但几乎所有患者都会复发。二线治疗通常有益，但缓解很少持久。我们开展了这项II期试验，以评估氟达拉滨、米托蒽醌和地塞米松（FND）对复发惰性淋巴瘤患者的治疗效果和毒性。
51例复发或难治性惰性淋巴瘤患者接受如下方案治疗：第1至3天静脉注射氟达拉滨25mg/m²/d，第1天静脉注射米托蒽醌10mg/m²，第1至5天静脉注射或口服地塞米松20mg/d。每4周重复治疗，最多8个疗程。在该试验后期，加入甲氧苄啶-磺胺甲恶唑（TMP-SMX）预防卡氏肺孢子虫（PCP）肺炎。
24例患者（47%）完全缓解（CR），24例（47%）部分缓解（PR）。CR患者的无失败生存期（FFS）中位数为21个月，PR患者为9个月。即使在老年患者、血清乳酸脱氢酶（LDH）或β2-微球蛋白水平高的患者以及接受过多种既往治疗方案的患者中，FND也显示出显著活性。主要毒性作用为骨髓抑制和感染；其他毒性作用较轻。12%的疗程发生感染。几乎一半的感染为确诊或疑似机会性感染，包括6例带状疱疹和2例确诊的PCP肺炎。
FND联合方案对复发或难治性惰性淋巴瘤患者具有高度活性，CR率高。由于存在机会性感染风险，我们目前建议用TMP-SMX进行预防，并建议对发生机会性感染的患者停用皮质类固醇。
