Head and Neck Cancer
Conditions
Keywords
stage III squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx
Brief summary
RATIONALE: Drugs used in chemotherapy, such as docetaxel, cisplatin, fluorouracil, and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which regimen of chemotherapy and radiation therapy is most effective in treating head and neck cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of chemotherapy and radiation therapy in treating patients who have stage III or stage IV head and neck cancer.
Detailed description
OBJECTIVES: Primary * Compare 3-year survival of patients with previously untreated stage III or IV squamous cell carcinoma of the head and neck treated with induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil followed by radiotherapy and carboplatin or docetaxel vs radiotherapy and cisplatin only. Secondary * Compare 2-year progression-free status in patients treated with these regimens. * Compare 5-year survival of patients treated with these regimens. * Compare 3- and 5-year progression-free survival of patients treated with these regimens. * Compare the complete response rate in patients treated with these regimens. * Compare tumor site-specific survival in patients treated with these regimens. * Compare functional organ preservation in patients treated with these regimens. * Compare the toxicity of these regimens in these patients. * Compare the quality of life of patients treated with these regimens. * Correlate tissue and germline markers with response, local/regional control, and the development of distant metastases in patients treated with these regimens. OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil. Treatment repeats every 21 days for 3 courses. Patients achieving a pathologic complete response at the primary site and a clinical complete response in the neck then receive carboplatin once weekly and undergo concurrent radiotherapy once daily, 5 days a week, for 7 weeks. Patients with a partial response at the primary site (i.e., positive biopsy), stable disease, or radiographic evidence of persistent disease in the neck receive docetaxel once weekly for 4 weeks and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks. * Arm II: Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks. Quality of life is assessed at baseline and then at 3, 12, and 24 months. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 330 patients will be accrued for this study.
Interventions
DRUGcarboplatin
Given IV
DRUGcisplatin
Given IV
DRUGdocetaxel
Given IV
DRUGfluorouracil
Given IV
Sponsors
National Cancer Institute (NCI)
Dana-Farber Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
List of Inclusion Criteria: * Histologically or cytologically confirmed squamous cell carcinoma of the head and neck * Stage III or IV\* disease * One of the following primary tumor sites: * Oral cavity * No mandible invasion * Oropharynx * Hypopharynx * Larynx * The following primary tumor sites are excluded: * Nasal cavity * Paranasal cavity * Nasopharynx NOTE: \*No evidence of distant metastases by chest x-ray, abdominal ultrasound, or CT scan (for patients with liver function test abnormalities) or bone scan (for patients with local symptoms) * At least 1 uni- or bi-dimensionally measurable lesion PATIENT CHARACTERISTICS: Age * Over 18 Performance status * WHO 0-1 Life expectancy * Not specified Hematopoietic * Neutrophil count \> 1,500/mm\^3 * Platelet count \> 100,000/mm\^3 * Hemoglobin \> 10 g/dL Hepatic * Bilirubin normal * AST or ALT within eligibility range * Alkaline phosphatase within eligibility range Renal * Creatinine clearance \> 60 mL/min Cardiovascular * No unstable cardiac disease despite treatment * No myocardial infarction within the past 6 months Pulmonary * No chronic obstructive pulmonary disease, defined as requiring hospitalization for pneumonia or respiratory decompensation within the past year * Obstruction caused by the tumor allowed Neurologic * No symptomatic peripheral neuropathy \> grade 2 * No symptomatic altered hearing \> grade 2 * No history of significant neurologic or psychiatric disorders, including dementia or seizures Other * No active drug addiction, including alcohol, cocaine, or intravenous drugs within the past 6 months * No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, or other cancer curatively treated by surgery alone * No active, clinically significant, uncontrolled infection * No autoimmune disease requiring therapy * No unhealed or clinically active peptic ulcer disease * No hypercalcemia * No other serious illness or medical condition * No involuntary weight loss \> 25% of body weight within the past 2 months * HIV negative * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 3 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy Endocrine therapy * Not specified Radiotherapy * No prior radiotherapy Surgery * No prior organ transplantation * No prior surgery for this cancer * Biopsy allowed Other * More than 30 days since prior participation in another investigational study * No other concurrent anticancer therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 3-years | To compare the 3-year survival achieved by docetaxel/cisplatin/5-FU based sequential therapy with platinum based chemo radiotherapy in patients with locally advanced SCCHN. Overall survival is defined as the time from date of randomisation to death from any cause. Patients alive at the time of current analysis were censored at the date last known to be alive.Kaplan-Meier method was used to estimate overall survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival and Disease-specific Survival as Assessed by Disease Progression or Death and Log Rank Tests at the Median, and 2, 3, and 5 Years | 5 years | Progression free survival was defined as the time from date of randomisation to disease progression or death from any cause without progression whichever occurred first; otherwise, patients were censored at the date last known to be free of progression. |
Countries
Germany, United States
Participant flow
Recruitment details
Between August 24, 2004 and December 29, 2008 145 patients were enrolled across 16 sites.
Pre-assignment details
Patients were randomly assigned in a 1:1 ratio to recieve either induction chemotherapy with 3 cycles of TPF followed by concurrent chemoradiotherapy with either docetaxel or carboplatin or concurrent chemoradiotherapy alone with 2 cycles of bolus cisplatin.
Participants by arm
| Arm | Count |
|---|---|
| Arm I Patients receive induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil. Treatment repeats every 21 days for 3 courses. Patients achieving a pathologic complete response at the primary site and a clinical complete response in the neck then receive carboplatin once weekly and undergo concurrent radiotherapy once daily, 5 days a week, for 7 weeks. Patients with a partial response at the primary site (i.e., positive biopsy), stable disease, or radiographic evidence of persistent disease in the neck receive docetaxel once weekly for 4 weeks and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks.
cisplatin : Given IV
radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks
carboplatin : Given IV
fluorouracil : Given IV
docetaxel : Given IV | 70 |
| Arm II Patients receive cisplatin IV on weeks 1 and 4 and undergo concurrent radiotherapy once or twice daily, 5 days a week, for 6 weeks.
cisplatin : Given IV
radiation therapy : Patients undergo radiation therapy once or twice daily, 5 days a week, for up to 7 weeks | 75 |
| Total | 145 |
Baseline characteristics
| Characteristic | Arm I | Arm II | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 9 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 59 Participants | 66 Participants | 125 Participants |
| Age Continuous | 55 years STANDARD_DEVIATION 9 | 54 years STANDARD_DEVIATION 8 | 55 years STANDARD_DEVIATION 8.4 |
| Region of Enrollment Germany | 1 participants | 6 participants | 7 participants |
| Region of Enrollment United States | 69 participants | 69 participants | 138 participants |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 18 Participants |
| Sex: Female, Male Male | 64 Participants | 63 Participants | 127 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 70 / 70 | 75 / 75 |
| serious Total, serious adverse events | 56 / 70 | 29 / 75 |
Outcome results
Primary
Overall Survival
To compare the 3-year survival achieved by docetaxel/cisplatin/5-FU based sequential therapy with platinum based chemo radiotherapy in patients with locally advanced SCCHN. Overall survival is defined as the time from date of randomisation to death from any cause. Patients alive at the time of current analysis were censored at the date last known to be alive.Kaplan-Meier method was used to estimate overall survival
Time frame: 3-years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Overall Survival | 73 percent of patients |
| Arm II | Overall Survival | 78 percent of patients |
Secondary
Progression-free Survival and Disease-specific Survival as Assessed by Disease Progression or Death and Log Rank Tests at the Median, and 2, 3, and 5 Years
Progression free survival was defined as the time from date of randomisation to disease progression or death from any cause without progression whichever occurred first; otherwise, patients were censored at the date last known to be free of progression.
Time frame: 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Progression-free Survival and Disease-specific Survival as Assessed by Disease Progression or Death and Log Rank Tests at the Median, and 2, 3, and 5 Years | 67 percent of patients |
| Arm II | Progression-free Survival and Disease-specific Survival as Assessed by Disease Progression or Death and Log Rank Tests at the Median, and 2, 3, and 5 Years | 69 percent of patients |