[Phase I clinical trial of intravenous recombinant human lymphotoxin-alpha derivative].
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.
Wang
Feng-Hua
FH
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, P. R. China.
Li
Yu-Hong
YH
Li
Su
S
Jiang
Wen-Qi
WQ
Guan
Zhong-Zhen
ZZ
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
D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins