Phase I trial of concurrent chemoradiation with weekly nedaplatin in patients with squamous cell carcinoma of the uterine cervix.

Abstract

OBJECTIVE:

This phase I clinical trial for cervical carcinoma had three objectives: to evaluate the toxicity of a concurrent chemoradiation regimen featuring weekly nedaplatin; to determine the recommended dose of nedaplatin for a phase II concurrent chemoradiation trial; and to evaluate the formula for predicting area under the curve data for nedaplatin through pharmacokinetic studies.

PATIENTS AND METHODS:

Twelve patients with locally advanced squamous cell carcinoma of the uterine cervix were enrolled. Nedaplatin was administered once a week for 6 weeks. The starting dose of nedaplatin was 25 mg/m(2)/week, with increments of 5 mg/m(2)/week planned for each dose level. Three cases were enrolled at each of the dose levels. Radiation therapy was delivered with both external beam teletherapy and intracavitary brachytherapy with HDR-RALS. Volunteering patients underwent pharmacokinetics studies during the second course.

RESULTS:

Nedaplatin at a dose of 25, 30, and 35 mg/m(2) was safely administered for three cases at each dose level. At a dose of 40 mg/m(2), however, all three cases had Grade 3 neutropenia. Observed area under the curve value and predicted value was closely correlated, with differences between the two area under the curve values within 25%. All 12 cases achieved a clinical complete response, as evaluated with RECIST.

CONCLUSIONS:

Our recommended dose for a phase II trial of concurrent chemoradiation with weekly nedaplatin is 35 mg/m(2). The formula can predict unbound concentration of nedaplatin based on area under the curve within 25% error.

• Authors: Kohsuke Yoshinaga, Hitoshi Niikura, Yoshihiro Ogawa, Kenji Nemoto, Satoru Nagase, Tadao Takano, Kiyoshi Ito, Nobuo Yaegashi
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 104 Issue 1 Pg. 36-40 (Jan 2007) ISSN: 0090-8258 [Print] United States
• PMID: 16889822 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• Platinum
• nedaplatin

Topics

• Adult
• Aged
• Antineoplastic Agents (adverse effects, blood, pharmacokinetics, therapeutic use)
• Brachytherapy (methods)
• Carcinoma, Squamous Cell (blood, drug therapy, radiotherapy)
• Combined Modality Therapy
• Dose-Response Relationship, Drug
• Female
• Humans
• Middle Aged
• Organoplatinum Compounds (adverse effects, blood, pharmacokinetics, therapeutic use)
• Platinum (blood)
• Radioisotope Teletherapy (methods)
• Uterine Cervical Neoplasms (blood, drug therapy, radiotherapy)