Weekly bryostatin-1 in metastatic renal cell carcinoma: A phase II study

Naomi B. Haas, Mitchell Smith, Nancy Lewis, Lynn Littman, Gwen Yeslow, Indira D. Joshi, Anthony Murgo, Joyce Bradley, Robert Gordon, Wang Hao, Andre Rogatko, Gary R. Hudes

Research output: Contribution to journalArticle

Abstract

Purpose: We conducted a Phase II trial of bryostatin-1, an inhibitor of protein kinase C, in advanced renal cell carcinoma to measure toxicity, response rate, time to progression, and induction of cytokines. Experimental Design: A total of 32 patients (26 male and 6 female) received bryostatin-1 at 35-40 ̀g/m2 i.v. over 1 h on days 1, 8, and 15 of each 4-week cycle. Plasma interleukin-6, tumor necrosis factor-α, and C-reactive protein levels were assayed pretreatment, 1 and 23 h after completion of bryostatin-1 infusion at weeks 1 and 5. Results: Cycles (102) of bryostatin-1 were given (median 2, range 1-8). The most common grade 1 or 2 toxicities were myalgias (46.8%), fatigue (59.3%), and dyspnea (18.8%). Grade 3-4 toxicity included myalgias (40.6%), ataxia (9.3%), and dyspnea (15.6%). Four (12%) patients experienced cardiac events while on study (cardiac arrhythmias and congestive heart failure occurred in 2 patients, and 2 patients had fatal cardiac arrests). Of 32 patients evaluable for response, 2 (6.3%) had partial responses lasting 9 with 6 months. A total of 15 patients (46.8%) had stable disease, and 6 (18.8%) patients had stable disease for ≥6 months. Plasma interleukin-6 increased ≥2-fold over baseline measurements in 5 of 17 patients (29.4%) but did not correlate with response or toxicity. Conclusions: Although weekly bryostatin-1 at 35-40 μg/m2 produced a low proportion of objective responses, prolonged (>6 months) stable disease or partial remission in 25% of patients suggests that this agent, or other inhibitors of protein kinase C, may have a role in the treatment of renal cell carcinoma, perhaps in combination with other agents.

Original languageEnglish (US)
Pages (from-to)109-114
Number of pages6
JournalClinical Cancer Research
Volume9
Issue number1 I
StatePublished - Jan 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Weekly bryostatin-1 in metastatic renal cell carcinoma: A phase II study'. Together they form a unique fingerprint.

  • Cite this

    Haas, N. B., Smith, M., Lewis, N., Littman, L., Yeslow, G., Joshi, I. D., Murgo, A., Bradley, J., Gordon, R., Hao, W., Rogatko, A., & Hudes, G. R. (2003). Weekly bryostatin-1 in metastatic renal cell carcinoma: A phase II study. Clinical Cancer Research, 9(1 I), 109-114.