[Phase I clinical trial of intravenous recombinant human lymphotoxin-alpha derivative].

BACKGROUND &

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.