title: [Phase I clinical trial of intravenous recombinant human lymphotoxin-alpha derivative].
abstract: OBJECTIVE
  Intravenous recombinant human lymphotoxin-alpha derivative (rhLTalpha-Da) is a novel biological antitumor reagent developed in China. This study was to evaluate the tolerance of tumor patients to rhLTalpha-Da, confirm its maximum tolerable dose (MTD) in vivo, and to provide recommending dose for phase II trial.
  
  
  METHODS
  The dose escalation of rhLTalpha-Da was as follows: 10 microg.(m2.day)-1, 20 microg.(m2.day)-1, and 33 microg.(m2.day)-. Each group contained at least 3 patients. rhLTalpha-Da was solved in 5% GS (100 ml), and intravenously infused over 30 minutes daily for 5 consecutive days.
  
  
  RESULTS
  A total of 24 patients were enrolled. Grade I-III chill and fever were the most common adverse events, with the occurrence rate of 79.2% (19/24). Other adverse events observed were dyspnea (3/24), nausea/vomiting (3/24), headache (4/24), fatigue (2/24), hypotension (2/24), and skin discomfort at irradiation region (2/24). No obvious abnormity of liver and renal functions was observed. The dose-limiting toxicities (DLT), which occurred at dose level of 33 microg.(m2.day)-1, were grade III chill, grade III fever, and grade III dyspnea. Although there was no definite efficacy showed in this primary study, initial response to rhLTalpha-Da was seen on a minority of patients with cancers, including malignant melanoma, mycosis fungoides, and renal carcinoma.
  
  
  CONCLUSIONS
  The MTD of rhLTalpha-Da is 33 microg.(m2.day)-1. The recommended dose for phase II clinical trial is 20 microg.(m2.day)-1.
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, P. R. China.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Wang
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.forename: Wen-Qi
authors.initials: WQ
authors.lastname: Jiang
authors.forename: Zhong-Zhen
authors.initials: ZZ
authors.lastname: Guan
mesh_terms: D000328:Adult; D000368:Aged; D023341:Chills / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004417:Dyspnea / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008233:Lymphotoxin-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins