PHASE-I STUDY OF THE PLANT PROTEIN RICIN

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (2) , 862-865
Abstract
Phase I study was carried out with ricin, a plant toxin acting by inhibiting protein synthesis, on 54 cancer patients with advanced disease. Ricin was given as i.v. bolus injections every 2 wk at dose levels ranging from 4.5-23 .mu.g/sq m of estimated body surface area. Ricin was well tolerated at doses up to 18-20 .mu.g/sq m. At these levels and at higher levels, flu-like symptoms with fatigue and muscular pain appeared and, in some patients, nausea and vomiting occurred also. No myelosuppression was seen. Antibodies to ricin were detected in serum after 2-3 ricin injections. Ricin was eliminated from blood according to first order kinetics. At each dose level, the plasma concentrations, as well as the side effects, showed only minor differences between patients. The highest dose given, 23 .mu.g/sq m, gave plasma concentrations twice those found previously to be therapeutically effective in tumor-bearing mice. Of 38 evaluable patients, 1 patient with lymphoma had a partial response. Stable disease was observed in 4 patients with renal cancers, in 2 with soft tissue sarcomas, and in one patient each with mesothelioma, thyroid and rectal cancer. A dose of 23 .mu.g/sq m is recommended for Phase II trials of ricin.