TPF Arm Research Articles

β-Tubulin-II Expression Strongly Predicts Outcome in Patients Receiving Induction Chemotherapy for Locally Advanced Squamous Carcinoma of the Head and Neck: A Companion Analysis of the TAX 324 Trial

TAX 324 was a phase III trial comparing induction chemotherapy (IC) with docetaxel, cisplatin, and fluorouracil (TPF) with cisplatin and fluorouracil (PF) followed by concomitant chemoradiotherapy in locally advanced squamous cell cancer of the head and neck (LASCCHN). This study evaluates a series of tumor markers in pretreatment biopsies from that trial TAX 324 and correlates expression with survival. Pretherapy biopsy specimens were available for 265 of 501 participants. Expression of a series of six markers (p53, thymidylate synthase, glutathione s-transferase pi [GST-pi], Bcl 2, beta tubulin II [betaT-2], and HER2 neu) was evaluated by immunohistochemistry. For patients with low betaT-II expression, median overall survival (OS) was 58.6 months (95% CI, not reached [NR]), compared with 18.2 months for patients with high betaT-II expression (95% CI, 13.11 to 30.06: hazard ratio [HR], 2.39; 95% CI, 1.67 to 3.72; P < .0001). Progression-free survival in patients with low betaT-II expression was 43.2 months (95% CI, 24.4 to NR) versus 9.8 months (95% CI, 7.06 to 18.53) for high betaT-II expression, with a HR of 1.9 (95% CI, 1.43 to 2.77; P < .0001). The predictive value of betaT-II expression was greater in the TPF versus PF arm than in the PF arm. Increased tumor expression of betaT-II is strongly associated with adverse outcome in LASCCHN patients treated with IC, and our data suggest low expression of betaT-II may predict patients most likely to benefit from induction TPF therapy. Further, simple models which combine expression of betaT-II with a carefully defined set of additional immunohistochemical markers may have significant prognostic impact for patients with LASCCHN.

Economic evaluation of the TAX 324 trial comparing docetaxel plus cisplatin and 5-fluorouracil (TPF) versus standard treatment with cisplatin and 5-fluorouracil (PF) as induction chemotherapy followed by concurrent chemoradiation therapy in locally advanced squamous cell carcinoma of the head and neck (SCCHN)

6079 Background: The TAX 324 phase III trial showed that induction chemotherapy with TPF followed by chemoradiotherapy improves survival and time to progression in patients with locally advanced SCCHN compared with PF [Posner MR, et al. ASCO 2006]. A Markov state-transition model was developed to estimate the cost-effectiveness of TPF. Methods: The Markov model includes four health states (based on WHO criteria for measuring objective response): stable, responsive, progressive disease, and death. TAX 324 efficacy data were used to derive transition probabilities between health states. Adverse event rates were also derived from TAX 324. Data for resource utilization and costs from a UK perspective were derived from the literature and clinician inputs from an advisory board. The global score of the Health Related Quality of Life Questionnaire Core-30 (QLQ-C30) was mapped to the EQ-5D in order to derive utilities and quality adjusted life years (QALYs). Results: A patient in the TPF arm survived longer versus PF (5.4 vs. 2.7 years). Comparison of TPF vs. PF resulted in an incremental gain of 2.7 life years and 2.1 QALYs. The incremental discounted costs/QALY gained for TPF vs. PF was £1,988/QALY, which is below the £20,000 cost-effectiveness threshold suggested by NICE as a guide to the acceptability of a technology. At this threshold, there is a 96.1% probability that TPF is cost-effective compared with PF. Conclusion: Docetaxel, when given as induction chemotherapy followed by concurrent chemoradiotherapy in combination with cisplatin and 5-fluorouracil (TPF), leads to a substantial increase in life expectancy, and is cost-effective compared with PF for locally advanced SCCHN. No significant financial relationships to disclose.

Randomized phase III trial comparing induction chemotherapy using cisplatin (P) fluorouracil (F) with or without docetaxel (T) for organ preservation in hypopharynx and larynx cancer. Preliminary results of GORTEC 2000–01

5506 Background: Induction chemotherapy (CT) with PF followed by RT in case of objective response is an alternative to total laryngectomy (TL) for patients with locally advanced larynx (L) and hypopharynx (H) cancer. Data have suggested that T may add to the efficacy of PF. The objective of this trial was to determine whether the addition of T to PF could increase the L preservation rate. Methods: Patients with L and H cancer for whom surgical procedure required TL were randomized to receive PF or TPF. Inclusion criteria were: adequate organ function, WHO PS 0 or 1, age from 18 to 70, signed informed consent. Treatment arms were PF = P 100 mg/m2/d1 and F: 1000 mg/m2 continuous infusion (CI) d1 to 5, TPF = T: 75 mg/m2/d1, P: 75mg/m2/d1 and F: 750mg/m2 CI d1 to 5 for 3 cycles with 21 days interval. Patients with complete or partial response and who recovered normal L mobility received RT to 70 Gy. Non responders underwent TL followed by RT. The primary endpoint was 3-year larynx preservation rate. To detect an absolute difference of 15% the sample size was 210. Results: 220 patients were randomized (108 to PF, 112 to TPF). Patients characteristics (age, sex, PS, primary site, TN) were well balanced. The TPF arm showed greater grade 3–4 alopecia (19% vs 2%) and neutropenia (57% vs 35%) while the PF arm showed greater grade 3–4 mucositis (9% vs 4%) and febrile neutropenia (6% vs 2%).Compliance to CT was better in the TPF. The specified treatment was delivered in 81.2% of patients in the TPF vs 67.4%. The overall response rate (T and N) was 82.8% in the TPF vs 60.8% (p = 0.0013). 60.6% of patients achieved a complete endoscopic response vs 46.7%. L preservation was offered for 80% of patients in the TPF vs 57.6%. A high hemoglobin level (&gt;14 gr/l) and a compliance to treatment &gt;80% are associated with a better response rate. With a median follow up of 35 months the 3-year actuarial L preservation rate is 73% following TPF vs 63% using the PF regimen. Conclusion: In advanced L and H cancer, TPF demonstrated significantly superior overall response rate compared to the PF regimen. The TPF is better tolerated and preliminary results suggest that L preservation could be achieved for a higher proportion of patients. No significant financial relationships to disclose.