Long-term intravenous hydroxyurea infusions in patients with advanced cancer. A phase I trial

✍ Scribed by Martin S. Blumenreich; Michael J. Kellihan; U. Geetha Joseph; Kim A. Lalley; Eliza J. Sherrill; Daniel M. Sullivan; John T. Hamm; Patrick S. Gentile; Subash P. Sheth; Janell Seeger; Thomas M. Woodcock

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 384 KB
• Volume: 71
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(19930501)71:9<2828::aid-cncr2820710924>3.0.co;2-p

✦ Synopsis

Background. Hydroxyurea is an S-phase specific drug. Constant exposure of tumor cells with a low Sphase fraction to the agent may result in improved cell kill. Because of its short half-life, a continuous intravenous infusion may result in better tumor exposure than intake by mouth. The goal of this trial was to find the longest tolerable duration of a continued intravenous infusion of hydroxyurea (HU) given at escalating doses.

Methods. Eligible patients had histologically confirmed cancer without effective alternate therapy, normal blood counts, liver and kidney function. After giving informed consent, the infusion began via a permanent indwelling catheter utilizing a portable pump. Dose levels (in g/mZ/d) were 0.5 for level I, 1.0 for level II,1.66 for level 111, and 2.5 for level IV.

Results. Fourteen patients were entered. Five were men. Median age was 56 years of age (range: 32-67), median performance status 1 (range: 0-2). Diagnoses were as follows: colorectal cancer, seven: unknown primary site, three: breast cancer, two; melanoma, one: and adenoidcystic carcinoma, one. Nine patients were pretreated with chemotherapy. Three patients were entered per dose level, except on level I, were five were entered. The mean duration of infusion was 12 weeks on level I, 5 weeks on 11, 3 on 111, 1 on IV. Toxicity included leukopenia below 2.0 K/mm3 in one patient each on levels 111