Dose escalation study of docetaxel and nedaplatin in patients with relapsed or refractory squamous cell carcinoma of the esophagus pretreated using cisplatin, 5-fluorouracil, and radiation.
BACKGROUND
Definitive chemoradiation with cisplatin (CDDP) and 5-fluorouracil (5FU) has been playing an important role in the treatment of esophageal cancer, but some patients are not curable or have recurrent lesions. However, few chemotherapeutic regimens are available for such patients. Docetaxel and nedaplatin are active for esophageal cancer. We conducted a dose-escalation study of docetaxel and nedaplatin as second line-chemotherapy after definitive chemoradiation in patients with relapsed or refractory squamous cell carcinoma of the esophagus after chemoradiation.


METHODS
Nedaplatin was administered on day 1 and docetaxel was administered on days 1 and 15, every 4 weeks. Dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle.


RESULTS
Twelve patients were enrolled. At a docetaxel dose of 30 mg/m(2) and a nedaplatin dose of 80 mg/m(2), one grade 4 neutropenia occurred and caused one treatment break longer than 2 weeks, but there were few DLTs. At doses of 35 and 80 mg/m(2), respectively, two grade 4 neutropenias and one grade 2 thrombopenia occurred and caused three treatment breaks longer than 2 weeks. Therefore, the maximum tolerated dose was established at this dose level. Two grade 3 anorexias and one grade 3 nausea occurred, but other non-hematological toxicities were generally mild. Responses were seen in one-fourth of the 12 patients, including one complete remission.


CONCLUSIONS
The recommended doses of docetaxel and nedaplatin were 30 and 80 mg/m(2), respectively. This combination could be a potential second-line treatment for this target population.
Yoshioka
Takashi
T
Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. ytakashi@idac.tohoku.ac.jp
Sakayori
Masato
M
Kato
Shunsuke
S
Chiba
Natsuko
N
Miyazaki
Shukichi
S
Nemoto
Kenji
K
Shibata
Hiroyuki
H
Shimodaira
Hideki
H
Ohtsuka
Kazunori
K
Kakudo
Yuichi
Y
Sakata
Yuh
Y
Ishioka
Chikashi
C
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D005260:Female; D005472:Fluorouracil; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D012074:Remission Induction; D016879:Salvage Therapy; D043823:Taxoids / Q000008:administration & dosage
D009944:Organoplatinum Compounds; D043823:Taxoids; D000077143:Docetaxel; C053989:nedaplatin; D002945:Cisplatin; D005472:Fluorouracil