A randomized trial of intrapericardial (ip) bleomycin (BLM) after drainage for management of malignant pericardial effusion (MPE) in lung cancer patients (pts): Report of a Japan Clinical Oncology Group trial (JCOG 9811)

Abstract

7710 Background: This trial was aimed to evaluate the safety and efficacy of ip BLM instillation as compared to pericardial drainage alone in pts with MPE. Methods: Pts ≤ 75 y.o. with pathologically documented lung cancer, who had received pericardial drainage for clinical MPE within 72 hours of the enrollment, were eligible. Pts with chemo-naïve small cell cancer, major organ failure, or severe co-morbidity were excluded. Signed consent form was obtained. Pts were randomized to either Arm A: observation alone after drainage, or Arm B: ip BLM of 15mg, followed by additional ip BLM 10mg q48hours. Drainage tube was removed when daily drainage was ≤20mL; the protocol therapy was judged as primary failure, with no regulations on post-therapy, if this criteria could not be met after 7 days from enrollment. MPE was followed at 1,2,4,6 and 12 months by echocardiography. The primary endpoint was survival with MPE control (effusion failure-free survival, EFFS) at 2 months, assumed to be 60% vs. 30%. The trial was designed to provide 80% power with 5% one-sided alpha, with 80 cases. Results: From Aug./99 to Jan./06, 80 pts were enrolled, with 79 eligible. M:F=51:29, median age 60 y.o. (range: 39–75), 75 nonsmall histology, 53 with prior chemotherapy, and 20 with prior radiotherapy. Median drainage volume was 600 mL (range: 130–1930). Cytology of the effusion was positive in 58/76 examined. EFFS ( table ) tended to favor Arm B, with hazard ratio of 0.64 (one-sided p=0.030 by logrank test, 95% C.I. 0.40–1.03). No additional acute toxicities or complications were observed for Arm B. There were 2 cases with late constrictive complications in Arm B, but none was severe. The median survival was 79 days (A) and 119 days (B) (not significant). Conclusions: Although the difference of EFFS at 2 months was not statistically significant, BLM ip after pericardial drainage appears to be safe and effective in allover for management of MPE. No significant financial relationships to disclose. [Table: see text]