Comparison of carboplatin-paclitaxel to docetaxel-cisplatin-5-flurouracil induction chemotherapy followed by concurrent chemoradiation for locally advanced head and neck cancer.

OBJECTIVES: In head and neck squamous cell carcinoma (HNSCC), docetaxel, cisplatin and 5-fluorouracil (TPF) has become an accepted induction chemotherapy regimen. However, carboplatin-paclitaxel (CT) regimens have shown comparable outcomes. Here, we compared the outcomes of patients treated with either TPF or CT as induction chemotherapy followed by definitive chemoradiation. PATIENTS AND METHODS: We performed a single-institution retrospective analysis of patients with Stage III-IV HNSCC. From a database of 803 patients, we identified 143 patients treated with TPF or CT induction chemotherapy between 1999 and 2012. RESULTS: 53 patients and 90 patients received TPF or CT induction chemotherapy, respectively. The median follow-up was 18.9 months. The 1 year locoregional control was 80.5% for CT compared to 55.5% for TPF (HR 0.32, P=.0002). The 1 year progression free survival was 73.2% for CT compared to 60.7% for TPF (HR 0.57; P=.02). On multivariable analysis, CT remained significant for LRC (HR 0.28; P=0.04). TPF induction chemotherapy was associated with worse renal toxicity as measured by peak creatinine increases during induction chemotherapy (P=0.001). TPF was also associated with a trend toward more chemotherapy dose reductions or changes in systemic agents during concurrent chemoradiation (43.4% for TPF vs. 27.8% for CT; P=0.06). CONCLUSIONS: Compared to TPF induction chemotherapy, CT induction chemotherapy had at least similar if not better LRC and PFS in patients while having less renal toxicity. Thus, CT induction chemotherapy may benefit patients with locally advanced HNSCC by facilitating adequate chemoradiation regimens that enhanced disease control.

Validation of temporal optimization effects for a single fraction of radiation in vitro.

PURPOSE: To experimentally validate how temporal modification of the applied dose pattern within a single fraction of radiation therapy affects cell survival. METHOD AND MATERIALS: Using the linear-quadratic model, we have previously demonstrated that the greatest difference in cell survival results from comparing a temporal dose pattern delivering the highest doses during the middle of a fraction and the lowest at the beginning and end ("Triangle") to one with the lowest doses at the middle and the highest at the beginning and end ("V-shaped"). Also, these differences would be greatest in situations with low alpha/beta and large dose/fraction and fraction length. Two low (WiDr, PC-3) and one high (SQ-20B) alpha/beta cell lines were irradiated in six-well plates with 900 cGy over 20 min (900 cGy/20 min), one each with a Triangle and V-shaped dose pattern. WiDr cells were subjected to the same experiments with first 180 cGy/20 min, then 900 cGy/5 min. Cell survival was assessed using the clonogenic assay. RESULTS: At 900 cGy/20 min, irradiation with a V-shaped pattern resulted in an increased survival compared with use of a Triangle pattern of 21.2% for WiDr (p < 0.01), 18.6% for PC-3 (p < 0.025), and 4.7% for SQ-20B cells (p > 0.05). For WiDr cells at 180 cGy/20 min, this increase reduced to 2.7% (p > 0.05) and to -0.8% (p > 0.05) at 900 cGy/5 min. CONCLUSIONS: These results verify the assertions of the modeling study in vitro, and imply that the temporal pattern of applied dose should be considered in treatment planning and delivery.