Head and Neck Cancer
Conditions
Keywords
stage II lymphoepithelioma of the nasopharynx, stage II squamous cell carcinoma of the nasopharynx, stage III lymphoepithelioma of the nasopharynx, stage III squamous cell carcinoma of the nasopharynx, stage IV lymphoepithelioma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx
Brief summary
RATIONALE: Radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining high-dose radiation with chemotherapy may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining high-dose radiation therapy with chemotherapy in treating patients who have newly diagnosed stage II, stage III, or stage IV nasopharyngeal cancer.
Detailed description
OUTLINE: Cohorts of 10 patients receive the following treatment to assess for dose-limiting toxicity. Phase I * Radiotherapy: Patients receive radiotherapy once daily 5 days a week for 6 weeks beginning on day 1. * Concurrent chemotherapy: Patients receive cisplatin IV over 20-30 minutes on days 1-5 and 22-26. * Adjuvant chemotherapy: Approximately 2-5 weeks after the completion of radiotherapy, patients receive fluorouracil IV continuously on days 1-4 and cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. In the absence of dose-limiting toxicity in 1 whole cohort of patients, study proceeds to phase II. Phase II * Patients are treated as in phase I. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
Interventions
DRUGcisplatin
DRUGfluorouracil
PROCEDUREadjuvant therapy
RADIATIONradiation therapy
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed nasopharyngeal cancer * Stage II-IVB * Newly diagnosed * No distant metastases PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Karnofsky 60-100% Life expectancy * Not specified Hematopoietic * WBC at least 3,000/mm\^3 * Granulocyte count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Hemoglobin at least 8 g/dL Hepatic * Bilirubin no greater than 1.5 times upper limit of normal (ULN) * Alkaline phosphatase no greater than 2.5 times ULN * AST no greater than 2.5 times ULN Renal * Creatinine no greater than 1.5 mg/dL * Creatinine clearance at least 60 mL/min * Calcium no greater than 11.5 mg/dL Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Medically able to tolerate a definitive course of radiotherapy and the necessary immobilization * No other active malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy for this diagnosis * More than 3 years since other prior chemotherapy Endocrine therapy * Not specified Radiotherapy * No prior radiotherapy for this diagnosis * More than 3 years since other prior radiotherapy * No prior radiotherapy to the head and neck region Surgery * Not specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival Rate of Patients | up to 77 months | Patients will be followed indefinitely and will have standard screening for development of distant metastases, including physical exam, as well as liver function tests and a chest radiograph annually. Patients will be classified as progression free as long as they remain alive with local, regional or distant recurrence. |
| Local Control of Participants | every 3 months in the first year of follow-up, every 4 months in the second year, every 6 months in the third-fifth years and annually, thereafter. | Patients will be classified as controlled as long as there is no clinical or radiographic evidence of disease progression. Physical exam with fiberoptic nasopharyngoscopy will be performed approximately every 3 months in the first year of follow-up, every 4 months in the second year, every 6 months in the third-fifth years and annually, thereafter. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High-Dose Radiation Therapy Plus Chemotherapy Phase I
* Radiotherapy: Patients receive radiotherapy once daily 5 days a week for 6 weeks beginning on day 1.
* Concurrent chemotherapy: Patients receive cisplatin IV over 20-30 minutes on days 1-5 and 22-26.
* Adjuvant chemotherapy: Approximately 2-5 weeks after the completion of radiotherapy, patients receive fluorouracil IV continuously on days 1-4 and cisplatin IV over 20-30 minutes on days 1-5 and 22-26. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. In the absence of dose-limiting toxicity in 1 whole cohort of patients, study proceeds to phase II. Phase II
* Patients are treated as in phase I. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter. | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | High-Dose Radiation Therapy Plus Chemotherapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 25 |
| serious Total, serious adverse events | 19 / 25 |
Outcome results
Primary
Local Control of Participants
Patients will be classified as controlled as long as there is no clinical or radiographic evidence of disease progression. Physical exam with fiberoptic nasopharyngoscopy will be performed approximately every 3 months in the first year of follow-up, every 4 months in the second year, every 6 months in the third-fifth years and annually, thereafter.
Time frame: every 3 months in the first year of follow-up, every 4 months in the second year, every 6 months in the third-fifth years and annually, thereafter.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High-Dose Radiation Therapy Plus Chemotherapy | Local Control of Participants | Actuarial rate of local control | 91 percentage of participants |
| High-Dose Radiation Therapy Plus Chemotherapy | Local Control of Participants | Regional control | 91 percentage of participants |
| High-Dose Radiation Therapy Plus Chemotherapy | Local Control of Participants | Metastases-free survival | 91 percentage of participants |
| High-Dose Radiation Therapy Plus Chemotherapy | Local Control of Participants | Overall survival | 89 percentage of participants |
Primary
Survival Rate of Patients
Patients will be followed indefinitely and will have standard screening for development of distant metastases, including physical exam, as well as liver function tests and a chest radiograph annually. Patients will be classified as progression free as long as they remain alive with local, regional or distant recurrence.
Time frame: up to 77 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-Dose Radiation Therapy Plus Chemotherapy | Survival Rate of Patients | 33 months |