Tsimberidou Apostolia-Maria, Giles Francis, Romaguera Jorge, Duvic Madeleine, Kurzrock Razelle
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2004 Feb 1;100(3):574-80. doi: 10.1002/cncr.20009.
Interferon-alpha (IFN-alpha) and retinoids have shown nonoverlapping toxicity and each has shown antitumor activity in patients with lymphoma. The aim of the current study was to assess the toxicity, safety, and efficacy of IFN-alpha combined with isotretinoin in patients with advanced, refractory lymphoid malignancies.
Adults with biopsy-proven advanced lymphoid malignancy were treated. Patients with compromised bone marrow function (platelet counts as low as 30 x 10(9)/L) were eligible. Treatment was comprised of IFN-alpha at a starting daily dose of 3 mega units subcutaneously and isotretinoin orally starting at a dose of 1 mg/kg daily in 2 divided doses.
Forty-four patients were evaluable. Their median age was 57 years (range, 18-82 years). Eighteen patients had advanced cutaneous T-cell lymphoma, 6 patients had peripheral T-cell lymphoma, 14 patients had Hodgkin disease, and 6 patients had a variety of other lymphoid malignancies. Patients with Hodgkin disease had received a median of 6 previous therapies (range, 3-12 therapies) and patients with other lymphoid malignancies had received a median of 4 previous therapies (range, 1-9 therapies). The median duration of treatment was 4 months (range, 0.25-38 months). The overall response rate was 38.6% (complete response in 5 patients [11.3%] and partial response in 12 patients [27.3%]). The median response duration was 3 months (range, 1-95+ months). The most common toxicities were low-grade fever, flu-like symptoms, and fatigue (IFN-alpha effects); dry mouth and skin and hypertriglyceridemia (cis-retinoic acid effects); and thrombocytopenia (which generally occurred in patients with low baseline platelet counts).
IFN-alpha and isotretinoin combination therapy had antitumor activity and was well tolerated in heavily pretreated patients with lymphoid malignancies.
α干扰素（IFN-α）和维甲酸具有互不重叠的毒性，且二者在淋巴瘤患者中均已显示出抗肿瘤活性。本研究的目的是评估IFN-α联合异维甲酸治疗晚期难治性淋巴系统恶性肿瘤患者的毒性、安全性和疗效。
对经活检证实为晚期淋巴系统恶性肿瘤的成人患者进行治疗。骨髓功能受损（血小板计数低至30×10⁹/L）的患者符合条件。治疗包括起始剂量为每日3百万单位皮下注射的IFN-α和起始剂量为每日1mg/kg、分2次口服的异维甲酸。
44例患者可进行评估。他们的中位年龄为57岁（范围18 - 82岁）。18例患者患有晚期皮肤T细胞淋巴瘤，6例患者患有外周T细胞淋巴瘤，14例患者患有霍奇金病，6例患者患有其他多种淋巴系统恶性肿瘤。霍奇金病患者既往接受治疗的中位数为6次（范围3 - 12次），其他淋巴系统恶性肿瘤患者既往接受治疗的中位数为4次（范围1 - 9次）。中位治疗持续时间为4个月（范围0.25 - 38个月）。总缓解率为38.6%（5例患者完全缓解[11.3%]，12例患者部分缓解[27.3%]）。中位缓解持续时间为3个月（范围1 - 95 +个月）。最常见的毒性反应为低热、流感样症状和疲劳（IFN-α的作用）；口干、皮肤干燥和高甘油三酯血症（顺式维甲酸的作用）；以及血小板减少（一般发生在基线血小板计数低的患者中）。
IFN-α与异维甲酸联合治疗对淋巴系统恶性肿瘤患者具有抗肿瘤活性，且在经过大量预处理的患者中耐受性良好。
