title: Weekly bryostatin-1 in metastatic renal cell carcinoma: a phase II study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  A total of 32 patients (26 male and 6 female) received bryostatin-1 at 35-40 microg/m(2) i.v. over 1 h on days 1, 8, and 15 of each 4-week cycle. Plasma interleukin-6, tumor necrosis factor-alpha, 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 >or=6 months. Plasma interleukin-6 increased >or=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 microg/m(2) 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.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. nb_haas@fccc.edu
authors.forename: Naomi B
authors.initials: NB
authors.lastname: Haas
authors.forename: Mitchell
authors.initials: M
authors.lastname: Smith
authors.forename: Nancy
authors.initials: N
authors.lastname: Lewis
authors.forename: Lynn
authors.initials: L
authors.lastname: Littman
authors.forename: Gwen
authors.initials: G
authors.lastname: Yeslow
authors.forename: Indira D
authors.initials: ID
authors.lastname: Joshi
authors.forename: Anthony
authors.initials: A
authors.lastname: Murgo
authors.forename: Joyce
authors.initials: J
authors.lastname: Bradley
authors.forename: Robert
authors.initials: R
authors.lastname: Gordon
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Andre
authors.initials: A
authors.lastname: Rogatko
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hudes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D054713:Bryostatins; D002097:C-Reactive Protein / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D007783:Lactones / Q000008:administration & dosage / Q000627:therapeutic use*; D018942:Macrolides; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D054713:Bryostatins; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D007783:Lactones; D018942:Macrolides; D014409:Tumor Necrosis Factor-alpha; C046785:bryostatin 1; D002097:C-Reactive Protein; D011493:Protein Kinase C