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Neoadjuvant regimen prolonged OS in late-stage nasopharyngeal cancer
Neoadjuvant chemotherapy followed by concurrent chemoradiation appeared safe and effective in patients with locally advanced nasopharyngeal cancer, according to results from two phase 2 trials.
The trials included a combined 116 patients with newly diagnosed nasopharyngeal cancer who underwent treatment between January 2007 and July 2010. Fifty-two patients had stage III disease and 64 patients had nonmetastatic stage IVA or stage IVB disease.
All patients received neoadjuvant chemotherapy with docetaxel 75 mg/m2, cisplatin 75 mg/m2 and 5-fluorouracil 2,500 mg/m2 every 3 weeks for three cycles, plus concurrent chemoradiation with cisplatin 40 mg/m2 per week.
Median follow-up was 32.9 months.
Three-year OS rates were 94.8% (95% CI, 87,6-100) among patients with stage III nasopharyngeal cancer and 90.2% (95% CI, 81.8-98.6) among those with stage IV disease.
Three-year PFS rates were 78.2% (95% CI, 64.6-91.8) among patients with stage III disease and 85.1% (95% CI, 75.1-95.1) among patients with stage IV disease. Researchers also reported high rates of distant metastasis-free survival (90.5% for stage III and 88% for stage IV) and distant metastasis-free survival (93.9% for stage III and 100% for stage IV).
Adverse events included grade 3 and grade 4 neutropenia (55.2%) and nausea/vomiting (19.8%).
“This aggressive treatment combination remains investigational and can only be considered standard after confirmation by the already-initiated phase 3 randomized trial,” the researchers wrote.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
Back to TopKong and colleagues report on two trials of induction chemotherapy followed by chemoradiation in stage III and non-metastatic stage IV nasopharynx cancer. These types of nasopharynx cancers are virally mediated and treatment-responsive, and they have a long natural history. Historically, high cure rates have been obtained with chemoradiation followed by adjuvant platinum-based chemotherapy. Recent advances in disease monitoring with the use of Epstein-Barr virus (EBV) quantitative DNA assays have demonstrated that patients with early clearance of EBV DNA may have a superior outcome, and research is proposed to test whether patients with early clearance of EBV DNA may be candidates for chemoradiation without post-radiation adjuvant chemotherapy.
The researchers were interested in testing the use of chemotherapy prior to radiation, because of clinical experience demonstrating that not all patients will be able to receive post-radiation chemotherapy. They indeed demonstrated that all patients received two cycles of induction, and 89% received all three cycles of induction chemotherapy, so that in patients who require systemic therapy in addition to chemoradiation, it may well be preferable to administer this chemotherapy prior to the radiation. They also observed extremely high response rates to induction chemotherapy, although EBV DNA clearance data are not presented. Early clinical outcomes appear favorable, but the natural history of this cancer is such that longer follow-up is required. The study is also limited by absence of data regarding radiation quality assurance, especially in the context that intensity-modulated radiation therapy plans were simplified because of resource constraints.
The therapy studied in these trials is intensive, involving 9 weeks of induction therapy and 7 weeks of concurrent chemoradiation, and likely represents overtreatment for many patients with nasopharynx cancer. Prior nasopharynx cancer trials, as well as two recent trials of TPF induction in locally advanced non-nasopharynx head and neck cancers, have not demonstrated a benefit for the use of induction chemotherapy in unselected patients. Until we have learned how to identify patients at high risk for treatment failure, and how to incorporate EBV response into risk stratification, further intensification of treatment of stage III nonmetastatic stage IV nasopharynx cancer is not warranted.