A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer.
OBJECTIVE
To determine the recommended dose (RD) of cis-diammine-glycolatoplatinum (nedaplatin) when given concurrently with 5-FU and high dose radiation therapy in the treatment of esophageal cancer. The purpose of the phase II trial is to determine efficacy and further define the side effect profile.


METHODS
Twenty-six patients with clinical stage I to IVA squamous cell carcinoma of the esophagus were enrolled in a non-surgical treatment comprised of a fixed dose of fluorouracil (400 mg/m2 administered as continuous intravenous infusion on days 1-5 and days 8-12) plus escalating doses of nedaplatin (40 mg/m2 in level 1, 50 mg/m2 in level 2, or 60 mg/m2 in level 3 on days 1 and 8), repeated twice every 3 weeks with concurrent radiotherapy (60 Gy).


RESULTS
Between July 1998 and February 2004, a total of 26 patients entered this trial, all of whom were considered evaluable for toxicity assessment. In phase I of the study, 12 patients were treated in sequential cohorts of three to six patients per dose level. The maximum tolerated dose was reached at level 3 with two grade 4 neutropenia and one grade 4 thrombocytopenia. Thus, the recommended dosing schedule is level 2. Of the 20 patients treated at the RD level 2, including 6 patients of the RD phase I portion, 8 out of 20 patients (40%) had grade 3-4 neutropenia, 5 patients (25.0%) had grade 3-4 thrombocytopenia, 4 patients (20.0%) had grade 3 anemia and 4 patients (20.0%) had grade 3-4 esophagitis. Other toxicities were relatively mild and usually of grade 2 or less. Objective responses were noted in the 26 patients (overall response rate, 88.5%) including 11 (42.3%) complete remissions. The 1- and 3-year survival rates were 65.1 and 37.2%, respectively, with a median survival time of 21.2 months.


CONCLUSIONS
The combination of nedaplatin and 5-FU with radiation is a feasible regimen that shows promising antitumor activity with an acceptable safety profile in patients with esophageal cancer.
Sato
Yasushi
Y
Fourth Department of Internal Medicine, Sapporo Medical University, South 1 West 16, Chuo-ku, 060-8543, Sapporo, Japan.
Takayama
Tetsuji
T
Sagawa
Tamotsu
T
Okamoto
Tetsuro
T
Miyanishi
Koji
K
Sato
Tsutomu
T
Araki
Hironobu
H
Iyama
Satoshi
S
Abe
Seiichiro
S
Murase
Kazuyuki
K
Takimoto
Rishu
R
Nagakura
Hisayasu
H
Hareyama
Masato
M
Kato
Junji
J
Niitsu
Yoshiro
Y
D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D004941:Esophagitis / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods*; D012074:Remission Induction; D012720:Severity of Illness Index; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; C053989:nedaplatin; D005472:Fluorouracil