Combination Chemotherapy and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

University of Minnesota (UMN)

Status and phase

Terminated

Phase 2

Conditions

Head and Neck Cancer

Treatments

Drug: fluorouracil

Radiation: radiation therapy

Procedure: conventional surgery

Biological: pegfilgrastim

Biological: filgrastim

Drug: docetaxel

Drug: cisplatin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00352118

UMN-0502M67486

2005LS012

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy works in treating patients with locally advanced head and neck cancer. The doctor also wants to find out if patients who receive this treatment need a feeding tube 1 year after starting treatment.

Full description

OBJECTIVES:

Primary

Determine feeding tube dependency at 12 months in patients with locally advanced head and neck cancer treated with induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil followed by cisplatin and reduced-dose radiotherapy.

Secondary

Determine the progression-free, disease-free, and overall survival of patients treated with this regimen.
Determine the pattern of failure in patients treated with this regimen.
Evaluate the quality of life of patients treated with this regimen.
Assess pre- and post-treatment swallowing ability of patients and the impact on their quality of life.

Tertiary

Quantify salivary flow rates of patients receiving chemotherapy with radiotherapy for head and neck malignancy.
Evaluate the quality of saliva by examining total protein concentrations.
Quantify proangiogenic cytokines (interleukin [IL]-1, IL-6, IL-8, and vascular endothelial growth factor) in the saliva of these patients.
Determine the degree of mucositis and xerostomia of patients receiving chemotherapy with radiotherapy for head and neck malignancy.
Compare salivary flow rates with the grade of mucositis and xerostomia of patients receiving chemotherapy with radiotherapy for head and neck malignancy.

OUTLINE: This is a pilot study.

Induction therapy: Patients receive docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 followed by fluorouracil IV continuously on days 1- 4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 5-14 or pegfilgrastim SC on day 5. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a partial or clinical complete response proceed to chemoradiotherapy 3 weeks later.
Chemoradiotherapy: Patients receive cisplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent reduced-dose radiotherapy 5 days a week for 6 weeks.
Surgery: Approximately 6 to 8 weeks after completing chemoradiotherapy, patients with residual neck disease or disease initially staged at N2 or greater undergo neck dissection.

Saliva is collected periodically to measure flow rates and quality; quantify proangiogenic cytokines (interleukin [IL]-1, IL-6, IL-8 and vascular endothelial growth factor); and examine the grade of mucositis and xerostomia.

Quality of life is assessed at baseline, before chemoradiotherapy, 1 month after the last radiation treatment, every 3 months for 1 year, and then every 6 months for 1 year.

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Enrollment

4 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically confirmed squamous cell carcinoma of the head and neck
- Stage IVA or IVB disease
  - Stage III disease allowed provided patient may benefit from organ preservation or patient refused surgery
Measurable or evaluable disease
ECOG performance status 0-2
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Creatinine ≤ 1.5 mg/dL OR glomerular filtration rate ≥ 60 mL/min
Bilirubin normal
Alkaline phosphatase (AP) and AST or ALT must be within the following ranges:
- AP normal AND AST or ALT ≤ 5 times upper limit of normal (ULN)
- AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
- AP ≤ 5 times ULN AND AST or ALT normal

Exclusion criteria

Salivary gland, sinus, or nasopharyngeal primary disease
Evidence of distant metastatic disease
Pregnant or nursing
Positive pregnancy test (Fertile patients must use effective contraception during study treatment and for 3 months after completion of study treatment)
Other malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other malignancy in which stage and nature of disease is such that it is unlikely to affect survival for the next 3 years
Peripheral neuropathy ≥ grade 2
Hearing loss ≥ grade 2
Severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 and/or cisplatin or other platinum analogs
Poor nutritional status, in the opinion of the investigator
Active infection
Active ischemic heart disease
Myocardial infarction within the past 6 months
Prior radiotherapy above the clavicles
Prior chemotherapy
Prior surgery to the primary tumor except biopsy
Concurrent amifostine or other investigational agents