Phase I trial of combination chemotherapy with docetaxel, cisplatin and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer.
BACKGROUND
we investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin, and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer (HNC).


METHODS
treatment consisted of docetaxel (Taxotere) at doses of 50, 60, and 70 mg/m(2); cisplatin at 70 mg·m(2)/day on day 1; and S-1 twice daily on days 1-14 at doses of 40, 60, and 80 mg·m(2)/day, repeated every 3 or 4 weeks.


RESULTS
forty patients were enrolled. MTD was not reached until level 4. Subjects at expanded dose were limited to patients with locally advanced disease. Two dose-limiting toxic effects (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg·m(2)/day, every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 patients treated at dose level 6 (TPS: 70/70/60 mg·m(2)/day, every 3 weeks), 2 DLTs were seen. Six achieved a complete response and 22 a partial response, giving a response rate of 70%.


CONCLUSIONS
TPS was well tolerated. The recommended phase II dose as induction chemotherapy for locally advanced HNC was determined as 70/70/60 mg·m(2)/day every 3 weeks. Antitumor activity was highly promising and warrants further investigation.
Tahara
M
M
Division of Digestive Endoscopy and Gastrointestinal Oncology. Electronic address: matahara@east.ncc.go.jp.
Araki
K
K
Division of Hematology and Medical Oncology.
Okano
S
S
Division of Digestive Endoscopy and Gastrointestinal Oncology.
Kiyota
N
N
Division of Digestive Endoscopy and Gastrointestinal Oncology.
Fuse
N
N
Division of Digestive Endoscopy and Gastrointestinal Oncology.
Minashi
K
K
Division of Digestive Endoscopy and Gastrointestinal Oncology.
Yoshino
T
T
Division of Digestive Endoscopy and Gastrointestinal Oncology.
Doi
T
T
Division of Digestive Endoscopy and Gastrointestinal Oncology.
Zenda
S
S
Division of Radiation Oncology.
Kawashima
M
M
Division of Radiation Oncology.
Ogino
T
T
Division of Radiation Oncology.
Hayashi
R
R
Division of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Minami
H
H
Division of Hematology and Medical Oncology.
Ohtsu
A
A
Division of Digestive Endoscopy and Gastrointestinal Oncology.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
D004338:Drug Combinations; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid; D002945:Cisplatin