199例转移性黑色素瘤或肾细胞癌患者接受高剂量白细胞介素-2治疗的心肺毒性

Cardiopulmonary toxicity of treatment with high dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal cell carcinoma.

作者信息

White R L, Schwartzentruber D J, Guleria A, MacFarlane M P, White D E, Tucker E, Rosenberg S A

机构信息

Surgery Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892.

出版信息

Cancer. 1994 Dec 15;74(12):3212-22. doi: 10.1002/1097-0142(19941215)74:12<3212::aid-cncr2820741221>3.0.co;2-i.

DOI:10.1002/1097-0142(19941215)74:12<3212::aid-cncr2820741221>3.0.co;2-i

PMID:7982185

Abstract

BACKGROUND

Administration of recombinant interleukin-2 (rIL-2) can mediate tumor regression in patients with metastatic melanoma and renal cell carcinoma. In response to recent FDA approval of high dose rIL-2 for use in renal cell carcinoma, the authors recent experience with the cardiopulmonary toxicity associated with high dose IL-2 therapy is reviewed.

METHODS

The treatment courses of all patients receiving high dose intravenous bolus rIL-2 from January, 1988, until December, 1992, were evaluated for cardiopulmonary toxicity.

RESULTS

One hundred ninety-nine patients received 310 courses of treatment. There were no treatment-related deaths. Respiratory distress occurred in 3.2% of the courses, requiring intubation in one patient. Three obtunded patients were endotracheally intubated for airway control. Arrhythmias occurred in 6% of the courses (18 patients) with hypotension developing in two of the 199 patients as a result. Eleven of these patients were retreated and recurrent atrial fibrillation developed in two. One episode of significant ventricular tachycardia was noted. Hypotension occurred in 53% of courses; no patients developed hypotension unresponsive to vasopressors. There were no myocardial infarctions; however, 2.5% of patients experienced elevated creatine phosphokinase levels associated with elevated MB isoenzymes attributed to cardiac toxicity. Only one of these patients developed symptoms. Response rates of 19.6% and 15.7% were noted in patients with renal cell carcinoma and melanoma, respectively. Hypotension requiring vasopressors was associated with a significantly improved rate of response in patients with melanoma compared with patients not requiring vasopressors (23.2% vs. 6.5%, P2 = 0.037).

CONCLUSIONS

Although high dose intravenous rIL-2 therapy can be associated with cardiopulmonary toxicity, toxic side effects generally are not severe and are rapidly reversible.

摘要

背景

重组白细胞介素-2（rIL-2）的应用可使转移性黑色素瘤和肾细胞癌患者的肿瘤消退。鉴于美国食品药品监督管理局（FDA）最近批准高剂量rIL-2用于肾细胞癌治疗，本文作者回顾了高剂量IL-2治疗相关的心肺毒性方面的近期经验。

方法

对1988年1月至1992年12月期间所有接受高剂量静脉推注rIL-2治疗的患者疗程进行心肺毒性评估。

结果

199例患者接受了310个疗程的治疗。无治疗相关死亡病例。3.2%的疗程出现呼吸窘迫，其中1例患者需要插管。3例意识不清患者接受气管插管以控制气道。6%的疗程（18例患者）出现心律失常，199例患者中有2例因此发生低血压。其中11例患者接受再次治疗，2例出现复发性房颤。记录到1次显著的室性心动过速发作。53%的疗程出现低血压；无患者出现对血管升压药无反应的低血压。无心肌梗死病例；然而，2.5%的患者肌酸磷酸激酶水平升高，同时伴有因心脏毒性导致的MB同工酶升高。这些患者中只有1例出现症状。肾细胞癌和黑色素瘤患者的缓解率分别为19.6%和15.7%。与不需要血管升压药的黑色素瘤患者相比，需要血管升压药的低血压患者缓解率显著提高（23.2%对6.5%，P2 = 0.037）。