Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer
This study is being performed utilizing two cycles of Paclitaxel and Carboplatin, plus low doses radiation as initial therapy prior to other treatment (surgery or radiation). The study is assessing if utilization of low doses radiation as a chemoenhancer will further increase the response rate seen with initial therapy.
Squamous Cell Carcinoma
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer|
- Response rate [ Time Frame: assessed at baseline and once between days 42 and 56, then repeated every 6 months until disease progression ] [ Designated as safety issue: No ]
- Pathologic complete responses [ Time Frame: assessed between 3 and 24 hours after the last dose of radiation ] [ Designated as safety issue: No ]
- Toxicity [ Time Frame: assessed starting day 1 through study completion day 56 or until toxicities resolve ] [ Designated as safety issue: Yes ]
- Quality of Life [ Time Frame: assessed pre-study and once between study days 42 and 56 ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: throughout study treatment duration and then every 3 months after study completion ] [ Designated as safety issue: No ]
|Study Start Date:||September 2002|
|Estimated Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
50 cGy on days 1, 2, 8, 15, 22, 23, 29 & 36 of chemotherapyDrug: Paclitaxel
75 mg/m2 intravenously over one hour on Days 1, 8, 15, 22, 29 and 36Drug: Carboplatin
AUC of 6 on Days 1 & 22
Squamous cell cancers of the head and neck (SCCHN) 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 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. 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 radiation and alternating chemotherapy and radiation.
One novel approach to capitalizes on the synergy between radiation and chemotherapy is the use of low doses fractionated radiation (LDFRT) as a chemotherapy enhancer. In vitro data suggests that LDFRT enhances the response of both p53 wild type and p53 mutant cancer cell lines to chemotherapy. Not only was the cell death fraction increased, but there was no development of radioresistance in the cell lines studies when low doses of radiation were utilized. This strategy was translated into a clinical trial using four 80-cGy fractions of radiation with Carboplatin and Paclitaxel. Preliminary results have produced an impressive 85% response rate and this neoadjuvant regimen was safe and easy to deliver in patients with locally advanced SCCHN patients. In recently published work by Belani, a regimen using Carboplatin every four weeks combined with weekly Paclitaxel improved response rates in non-small cell lung cancer. The delivery of chemotherapy on a weekly schedule would be of particular benefit when adding LDFRT, because tumor cells could be exposed to LDFRT on multiple occasions per cycle of induction therapy, without the theoretic development of radioresistance. We propose to expand our understanding of LDFRT and chemotherapy by using two cycles of Paclitaxel and Carboplatin in a modification of the Belani regimen, plus LDFRT as induction therapy prior to definitive treatment (surgery or radiation). It is hoped that using LDFRT as a chemoenhancer will further increase the response rate seen with induction therapy in this population of patients.