Paclitaxel, Carboplatin and Radiotherapy as Induction Therapy in Locally Advanced Head and Neck Cancer
Squamous Cell Carcinoma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Paclitaxel, Carboplatin and Radiotherapy as Induction Therapy in Locally Advanced Head and Neck Cancer|
- Response Rate to Induction Chemotherapy Prior to Definitive Therapy (Surgery or Radiation) [ Time Frame: assessed pre-study and once between days 36-57 ] [ Designated as safety issue: No ]Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
- Frequency of Severe (>/= Grade 3) Toxicities [ Time Frame: assessed starting on day 1 through study day 58 or until toxicity resolves ] [ Designated as safety issue: Yes ]
- 5 Year Overall Survival Rates [ Time Frame: 5 years post study ] [ Designated as safety issue: No ]
- 5 Year Disease-specific Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]Outcome is calculated from the time of enrollment to the time of death due to disease under study or survival to 5 years without death from disease under study, whichever occurs first.The 5-year rates of disease-specific survival were calculated using the Kaplan-Meier method.
- 5 Year Progression Free Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
|Study Start Date:||May 2000|
|Study Completion Date:||October 2012|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Experimental: Induction chemotherapy and radiation
Induction chemotherapy with low dose radiation
80 centigray (cGy) on Day 1 & 2 and 22 & 23 of chemotherapyDrug: Paclitaxel
225 mg/m2 intravenously over three hours on Days 1 and 22
Other Name: TaxolDrug: Carboplatin
Area under the curve (AUC) of 6 will be given intravenously over 30 minutes on days 1 and 22
Other Name: Paraplatin, CBDCA
Cancers of the head and neck (H&N) comprise 5% of all cancers, with 40,000 new cases diagnosed annually. Surgery followed by irradiation or irradiation alone has been the standard of care for locally advanced Stage III and IV patients. With this approach, fewer than 30% of patients achieve long-term remission, and most recur locoregionally. Neoadjuvant chemotherapy has been administered prior to definitive therapy with response rates ranging from 60-90%; with pathologic complete response (CR) rates documented in 30-70% of clinical responders. However, large randomized trials have shown no improvement in overall survival.
Because induction chemotherapy alone does not appear to improve long-term disease free survival in advanced head and neck cancers, concomitant chemotherapy and radiation has been pursued in patients with locally advanced head and neck cancers. Improved disease-free survival has been demonstrated with a variety of agents. The concept of synergy between radiation and chemotherapy is well established in vitro. Various schedules of radiation and chemotherapy have been utilized including weekly chemotherapy during radiation, chemotherapy given every three weeks during hyperfractionated radiation and alternating chemotherapy and radiation.
One exciting new chemotherapeutic agent, Paclitaxel has been shown to radiosensitize cancer cell lines in vitro. Recent studies have added Carboplatin to Paclitaxel in tandem or concurrently with radiation in hopes of improving response rates. From in-vitro data, it appears that the optimum schedule for the combination of Paclitaxel and radiation is to first induce G2/M arrest with Paclitaxel and follow this with radiation therapy. In a recent study by Chendil, et al, a novel radiation scheme appeared to enhance the response of both p53 wild type and p53 mutant cancer cell lines to chemotherapy. In vitro data with Carboplatin also indicates an additive effect when given prior to irradiation using various cell lines. What has not been evaluated, is whether a neoadjuvant regimen of Paclitaxel and Carboplatin followed by 4 small fractions of radiation can be given safely and effect an improved response rate in patients with bulky T2, Stage III and IV H&N cancer. We propose the use of two cycles of Paclitaxel and Carboplatin followed by four small fractions of radiation, prior to definitive treatment (surgery or radiation). It is hoped that using radiation as a chemoenhancer will increase the response rate to induction therapy in this population of patients.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00176254
|Principal Investigator:||Susanne Arnold, MD||University of Kentucky|