A three-drug treatment for head and neck cancer (HNC) improves long-term survival so significantly that researchers are calling for the trio to become the standard of care for patients suitable for first-line therapy.
The study that yielded this positive news was a long-term look at the TAX 324 open-label, randomized phase 3 trial. The original project compared three cycles of induction chemotherapy with docetaxel (Taxotere), cisplatin (Platinol, generics), and fluorouracil—a regimen referred to as TPF—versus cisplatin and fluorouracil (PF) in the treatment of locally advanced (stage III or IV) head and neck cancer.
Locally advanced squamous cell carcinoma (SCC) of the head and neck is potentially curable in most patients, but only about half live for 3 years after standard therapy, and 40% to 60% eventually develop locoregional recurrences, distant metastases, or second primary tumor. Initial results from the TAX 323 trial in unresectable disease and the TAX 324 trial in both resectable and unresectable disease have shown that adding docetaxel to PF induction chemotherapy increases survival in locally advanced head and neck cancer over a median of 42 months’ follow-up (minimum of 2 years’ follow-up).
Jochen H. Lorch, MD, MSc, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and others working on behalf of the TAX 324 Study Group sought to determine whether the survival benefit endured beyond the follow-up period used in the initial analysis. This information is important because as Dr. Lorch and fellow researchers note in The Lancet Oncology, “5-year analyses have often revealed reduced survival and changes in outcomes in trials in head and neck cancer.”
PF patients received intravenous cisplatin 100 mg/m2, followed by fluorouracil 1,000 mg/m2 per day as a continuous 24-hour infusion for 5 days. TPF patients received docetaxel 75 mg/m2 followed by intravenous cisplatin 100 mg/m2 and fluorouracil 1,000 mg/m2 per day, infused continuously over 24 hours for 4 days. The induction chemotherapy was given every 3 weeks for three cycles, with chemoradiotherapy beginning 3 to 8 weeks after the start of the third cycle.
A total of 501 participants had been recruited from 55 centers across the United States, Canada, Argentina, and Europe between May 21, 1999, and December 3, 2003. In the initial analysis of December 2005, 267 patients were still living and 234 had died. At that point induction chemotherapy with TPF was shown to significantly improve survival compared with PF.
By December 1, 2008, 171 patients were still alive, 35 more had died, and 61 were lost to follow-up. Because Dr. Lorch and co-investigators found no sufficient evidence that loss to follow-up equated to death, they deemed those 61 people to be alive, and used their information from the initial analysis in 2005 for the updated assessment.
During a minimum follow-up period of 5 years (median: 6 years), “the survival advantage seen in the original report was sustained,” affirmed Dr. Lorch’s team. Overall survival was 26% better after treatment with TPF versus PF: Estimated 5-year survival rate was 52% in the TPF group and 42% in the PF group. Median survival was 70.6 months and 34.8 months, respectively.
The investigators point out that their study had several limitations: TAX 324 was a prospective, randomized trial, but the data for this follow-up analysis were gathered retrospectively. Survival information was available for 88% of the participants, but reliable data on tracheostomy and gastric feeding tubes were difficult to obtain for all patients, restricting interpretation of results.
The authors contend that patients who are candidates for induction chemotherapy should be treated with TPF. ONA