[Phase I Study of RA-700. RA-700 Clinical Study Group].
An antitumor substance, RA-700, isolated from Rubia akane or Rubia cordifolia has the novel structure. Phase I clinical study was conducted by the RA-700 clinical study group consisting of 6 institutions. A single dose administration and 5-day schedule administration were evaluated with 14 patients respectively. RA-700 was given from 0.2 to 1.4 mg/m2 in single i.v. dose study, from 0.4 to 2.0 mg/m2 in 5-day i.v. schedule study. Nausea and vomiting, fever, stomachache, mild hypotension and slight abnormality of electric-cardiogram were observed as the toxicities. In pharmacokinetic study, the elimination half-lives (t1/2) of RA-700 in plasma were 55 min, of alpha-phase and 3.9 hrs. of beta-phase by single dose study, and 23-25 min. of alpha-phase and 6-14 hrs. of beta-phase by 5-day schedule study. Accumulation was not found by 5-day schedule administration, and metabolite were not observed in plasma and urine. It seems that RA-700 is metabolized by the liver and excreted in the feces. In conclusion, the maximum tolerated dose was 1.4 mg/m2 for 5-day schedule administration.
Majima
H
H
Chiba Cancer Center, Ichijokai Hospital.
Tsukagoshi
S
S
Furue
H
H
Suminaga
M
M
Sakamoto
K
K
Wakabayashi
R
R
Kishino
S
S
Niitani
H
H
Murata
A
A
Genma
A
A
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D010456:Peptides, Cyclic; C043548:RA VII