Head and Neck Neoplasms
Conditions
Keywords
Combined Modality Therapy, Neoadjuvant Therapy, Head and neck neoplasms
Brief summary
The purpose of this study is to evaluate the effectiveness and safety of neoadjuvant chemotherapy (chemotherapy given before radiotherapy) using cisplatin and docetaxel, followed by carboplatin given at the same time as radiotherapy in the treatment of locally advanced head and neck cancer.
Detailed description
Chemoradiotherapy has become the standard of care for patients with unresectable head and neck cancer, but there can be substantial added toxicity with chemoradiotherapy compared to radiation therapy alone. Neoadjuvant therapy with cisplatin / 5-fluorouracil has demonstrated activity in this disease, and taxanes appear to improve response further. Docetaxel / cisplatin / 5-fluorouracil has been shown to be a highly active regimen. However, with the potential added toxicities of neoadjuvant chemotherapy, it is important to minimize toxicity while maintaining efficacy. Chemotherapeutic agents that are DNA cycle-specific like 5-fluorouracil are more stomatotoxic than those that are cell phase non-specific. Of note, several studies have suggested that docetaxel and cisplatin is a highly active combination when used for advanced disease or as neoadjuvant therapy . This study will therefore test the efficacy of neoadjuvant chemotherapy with cisplatin and docetaxel without 5-fluorouracil followed by chemoradiotherapy with carboplatin to determine whether promising response rates with modest toxicity can be achieved. Carboplatin will be used as the radiosensitizing agent during chemoradiotherapy to reduce nephrotoxicity and neurotoxicity as compared to further treatment with cisplatin.
Interventions
Docetaxel 75 mg/m2 intravenous every 3 weeks for 3 cycles Cisplatin 75 mg/m2 intravenous every 3 weeks for 3 cycles
RADIATIONRadiotherapy
70 Gy in 35 fractions to gross tumor and lymph node metastases
DRUGCarboplatin
Carboplatin AUC 1.5 intravenous weekly during radiotherapy
Sponsors
University of Vermont
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven locoregional Stage 4 squamous cell carcinoma of the oral cavity, larynx, oropharynx or hypopharynx * Measurable or evaluable disease * No distant metastases * Tumor should be surgically unresectable for cure or resection is considered inadvisable * Age \> 18 years * ECOG performance status 0, 1 or 2 * Life expectancy \> 2 months * Patients must have adequate organ and marrow function as defined below: * Leukocytes \> 3,000/mm3 * Absolute neutrophil count \> 1,500/mm3 * Platelets \> 100,000/mm3 * Hemoglobin \> 10.0g/dL * Total Bilirubin \<= institutional upper limit of normal * Aspartate aminotransferase \< 2.5 X institutional upper limit of normal * Alanine aminotransferase \< 2.5 X institutional upper limit of normal * Alkaline phosphatase \< 2.5 X institutional upper limit of normal * Creatinine \<= institutional upper limit of normal OR creatinine clearance \> 60 mL/min/1.73 m2 for patients with creatinine \> institutional upper limit of normal * Signed informed consent * Women of child-bearing potential and men must be willing and able practice adequate contraception prior to study entry and for the duration of study treatment
Exclusion criteria
* Previous chemotherapy for this malignancy * Previous radiotherapy to head and neck region * Other malignancy within last 5 years except for non-melanoma skin cancer * Uncontrolled intercurrent illness that would prevent delivery of protocol therapy * Peripheral neuropathy \> Grade 2 * Hypercalcemia * Patient is pregnant or lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response rate to neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer | 6 months after initiation of therapy |
Secondary
| Measure | Time frame |
|---|---|
| Response rate to neoadjuvant chemotherapy with docetaxel/cisplatin in locally advanced squamous head and neck cancer | 3 months after initiation of therapy |
| Response rate to chemoradiotherapy in locally advanced squamous head and neck cancer | 6 months after initiation of therapy |
| Toxicity of neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer | Every 3 weeks for 6 months (during therapy) |
| Progression free survival after neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer | Every 6 months |
| Overall survival after neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer | Every 6 months |
Countries
United States
Contacts
Primary ContactSteven M Grunberg, MD
Backup ContactMadhuri V Vithala, MD
Outcome results
None listed