A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas.
A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas.
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DOI：
10.1182/blood.v96.9.2934
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发表时间：
2000-11
期刊：
影响因子：
20.3
通讯作者：
O. Press;J. Eary;T. Gooley;A. Gopal;Stephen Liu;J. Rajendran;D. Maloney;S. Petersdorf;Sharon A. Bush;L. Durack;P. Martin;D. Fisher;B. Wood;J. Borrow;B. Porter;Justin P. Smith;D. Matthews;F. Appelbaum;I. Bernstein
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文献类型：
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作者：
O. Press;J. Eary;T. Gooley;A. Gopal;Stephen Liu;J. Rajendran;D. Maloney;S. Petersdorf;Sharon A. Bush;L. Durack;P. Martin;D. Fisher;B. Wood;J. Borrow;B. Porter;Justin P. Smith;D. Matthews;F. Appelbaum;I. Bernstein
复发性B细胞淋巴瘤是无法治愈的常规化疗和放疗，虽然一小部分患者可以治愈与高剂量的化疗和放疗和自体干细胞移植（ASCT）。我们进行了一项I/II期试验，以评估碘131（（131）I）-托西莫单抗（抗CD 20抗体）的最大耐受剂量（MTD），该剂量可与依托泊苷和环磷酰胺联合治疗复发性B细胞淋巴瘤患者，随后进行ASCT。52例患者接受1.7 mg/kg（131）I-托西莫单抗（185-370 MBq）示踪剂输注，随后进行系列定量γ照相机成像，并估计肿瘤部位和正常器官的辐射吸收剂量。10天后，患者接受1.7 mg/kg托西莫单抗治疗性输注，托西莫单抗标记有一定量的（131）I，经计算可将目标剂量的辐射（20-27戈伊）输送至重要的正常器官（肝、肾和肺）。患者保持辐射隔离，直到他们的全身放射性低于0.07 mSv/h在1米。然后给予依托泊苷和环磷酰胺，然后进行ASCT。与60 mg/kg依托泊苷和100 mg/kg环磷酰胺安全联合使用的（131）I-托西莫单抗的MTD可向关键正常器官递送25戈伊。所有治疗患者2年时的估计总生存期（OS）和无进展生存期（PFS）分别为83%和68%。这些结果与同期接受移植、外束全身照射、依托泊苷和环磷酰胺治疗的非随机对照组患者相比（2年OS为53%，PFS为36%），即使在多变量分析中调整混杂变量后也是如此。
Relapsed B-cell lymphomas are incurable with conventional chemotherapy and radiation therapy, although a fraction of patients can be cured with high-dose chemoradiotherapy and autologous stem-cell transplantation (ASCT). We conducted a phase I/II trial to estimate the maximum tolerated dose (MTD) of iodine 131 ((131)I)-tositumomab (anti-CD20 antibody) that could be combined with etoposide and cyclophosphamide followed by ASCT in patients with relapsed B-cell lymphomas. Fifty-two patients received a trace-labeled infusion of 1.7 mg/kg (131)I-tositumomab (185-370 MBq) followed by serial quantitative gamma-camera imaging and estimation of absorbed doses of radiation to tumor sites and normal organs. Ten days later, patients received a therapeutic infusion of 1.7 mg/kg tositumomab labeled with an amount of (131)I calculated to deliver the target dose of radiation (20-27 Gy) to critical normal organs (liver, kidneys, and lungs). Patients were maintained in radiation isolation until their total-body radioactivity was less than 0.07 mSv/h at 1 m. They were then given etoposide and cyclophosphamide followed by ASCT. The MTD of (131)I-tositumomab that could be safely combined with 60 mg/kg etoposide and 100 mg/kg cyclophosphamide delivered 25 Gy to critical normal organs. The estimated overall survival (OS) and progression-free survival (PFS) of all treated patients at 2 years was 83% and 68%, respectively. These findings compare favorably with those in a nonrandomized control group of patients who underwent transplantation, external-beam total-body irradiation, and etoposide and cyclophosphamide therapy during the same period (OS of 53% and PFS of 36% at 2 years), even after adjustment for confounding variables in a multivariable analysis.