Docetaxel, Cisplatin, and S-1 (TPS) Induction Chemotherapy in Locally Advanced Head and Neck Cancer

Head and Neck Cancer Clinical Trial

— TPSHNSCC  

Official title:

Multicenter Phase II Study of Weekly Docetaxel, Cisplatin, and S-1 (TPS) Induction Chemotherapy in Locally Advanced Squamous Cell Cancer of the Head and Neck

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01645748
• Other study ID #: CNUHH-MO-02
• Secondary ID: CNUHH
• Status: Completed
• Phase: Phase 2
• First received: July 12, 2012
• Last updated: July 18, 2012
• Start date: October 2008
• Est. completion date: March 2012

Study information

• Verified date: July 2012
• Source: Chonnam National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to evaluate the tolerability and efficacy of a combination of weekly docetaxel, cisplatin, and S-1 (weekly TPS) as induction chemotherapy in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Description:

Combination chemotherapy with cisplatin and fluorouracil (CF) is the standard treatment for patients with locally advanced squamous cancer of the head and neck. CF chemotherapy has been reported to increase survival and disease free survival in patients with unresectable disease when given before definitive radiotherapy, showing overall response rate as 75-85% including of CR rate of 25-35%. To improvement of treatment, docetaxel was incorporated into CF as induction treatment and it showed the prolongation of progression free survival and overall survival in large scale of randomized phase III trials, therefore triple combination induction regimen would be standard treatment in advanced head and neck cancer. Recently, the introduction of oral fluoropyrimidine showed similar or enhanced response rate, also favorable safety and convenience than intravenous fluoropyrimidine in advanced gastric cancer. Of the oral fluoropyrimidines, S-1 showed promising preliminary result in combination chemotherapy with cisplatin in head and neck cancer. In patients with advanced gastric cancer, phase I study of S-1, docetaxel and cisplatin combination chemotherapy was reported and the recommended doses were 40mg/m2 bid, 60mg/m2 (D1) and 60mg/m2 (D1), respectively. Therefore, the aim of this study was to evaluate the efficacy and safety of docetaxel, cisplatin and S-1 combination chemotherapy according to above dosage.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: March 2012
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• locally advanced stage III or IV squamous cell carcinoma of the larynx, oropharynx, or hypopharynx

• =18 years old

• absolute neutrophil count =1,500/µL, platelets =100,000/µL

• serum bilirubin <2.0 mg/dL

• creatinine <1.5 mg/dL

• serum transaminase levels less than twice the upper limit of normal

Exclusion Criteria:

• received previous chemotherapy

• another malignancy

• current or history of distant metastasis

• history of clinically significant cardiac disease within 6 months

• active serious infection

• nasopharyngeal carcinoma

• psychiatric illness that would preclude obtaining informed consent

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• S-1
S-1 is an oral fluoropyrimidine derivative, based on the concept of biochemical modulation. It consists in a molar ratio of 1:0.4:1: tegafur, a prodrug that is slowly metabolized to 5-fluorouracil; gimeracil, which reversibly inhibits dihydropyrimidine dehydrogenase. In patients with advanced gastric cancer, phase I study of S-1, docetaxel and cisplatin combination chemotherapy was reported and the recommended doses were 40mg/m2 bid (D1-D14), 60mg/m2 (D1) and 60mg/m2 (D1), respectively.
• S-1
Chemotherapy was comprised of docetaxel 30 mg/m2 on days 1 and 8, cisplatin 60 mg/m2 on day 1, and S-1 70 mg/m2 on days 1 to 14, with the regimen repeated every 21 days
• S-1
In patients with advanced gastric cancer, phase I study of S-1, docetaxel and cisplatin combination chemotherapy was reported and the recommended doses were 40mg/m2 bid (D1-D14), 60mg/m2 (D1) and 60mg/m2 (D1), respectively. Another phase II study of TPS as induction chemotherapy for locally advanced HNSCC was determined to be 70/70/60 mg·m2/d every 3 weeks. However, the rate of grade 3-4 neutropenia was 75% at this recommended dose. To reduce the hematologic toxicities, we used the docetaxel weekly. Therefore following regimen was evaluated in this study; docetaxel 30 mg/m2 (D1, D8), cisplatin 60mg/m2 (D1), S-1 70mg/m2 (D1-D14) every 3 weeks.

Locations

Country	Name	City	State
Korea, Republic of	Chonnam National University Hwasun Hospital	Gwangju	Jeollanamdo

Sponsors (4)

Lead Sponsor	Collaborator
Chonnam National University Hospital	Chonbuk National University, Chungbuk National University, Chungnam National University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate	After completion of CCRT, response rate was assessed. Patients underwent examination by an otolaryngologist, CT or MRI imaging of the primary tumor and neck. A biopsy of the primary site was recommended if possible. Tumor response was assessed according to the RECIST. For all patients with complete response (CR) on physical examination and CT or MRI scan, PET scan was performed for confirmation at 1 month after CT or MRI confirmation.	Response rate was evaluated 1 months after completion of CCRT	No
Secondary	Safety	Number of participants with adverse events as a measure of safety according to NCI-CTC version 3.0 was checked every 3 weeks up to 18 weeks.	From initiation of induction chemotherapy up to 18 weeks	Yes
Secondary	Progression free survival	Progression free survival means that the time from date of initiation of treatment until the date of first documented progression. Patients who completed treatment were followed by physician examination and CT or MRI scanning every 3 months for 1 year and then these checkup was done every 6 months for another one year.	From initiation of treatment up to 2 years	No
Secondary	Overall survival	Overall survival means that the time from initiation of treatment until the date of death from any cause up to 2 years	From initiatin of treatment up to 2 years	No