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


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.
Yoshinaga
Kohsuke
K
Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
Niikura
Hitoshi
H
Ogawa
Yoshihiro
Y
Nemoto
Kenji
K
Nagase
Satoru
S
Takano
Tadao
T
Ito
Kiyoshi
K
Yaegashi
Nobuo
N
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D001918:Brachytherapy / Q000379:methods; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D010984:Platinum / Q000097:blood; D011867:Radioisotope Teletherapy / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010984:Platinum; C053989:nedaplatin