The majority of patients diagnosed with nasopharyngeal carcinoma are at an advanced stage and have a poor prognosis. Concurrent platinum-based chemotherapy and radiation is currently the standard of care for these patients with high risk, but this treatment is associated with a high rate of relapse. In phase II trials, induction chemotherapy with gemcitabine and cisplatin were investigated with promising results for these patients.
In a phase III study published recently in The New England Journal of Medicine, investigators evaluated the impact of gemcitabine and cisplatin induction chemotherapy prior to concurrent chemoradiation, compared to concurrent chemoradiation alone, in 480 patients previously untreated with locoregionally advanced (stage III-IVB) nasopharyngeal carcinoma. At a median follow-up of 42.7 months, the study met its primary endpoint of improved recurrence-free survival (RFS). Patients receiving induction chemotherapy plus concurrent chemoradiation had a 3-year RFS of 85.3%, while those receiving chemoradiation alone had a 3-year RFS of 76.5% (HR 0.51, P = .001). The 3-year OS rate also improved from 90.3% in patients receiving concurrent chemoradiation alone to 94.6% in patients receiving induction chemotherapy prior to concurrent chemoradiation (HR 0.43). This survival improvement corresponds to a 40% reduction in the risk of death.
Induction chemotherapy was associated with higher rates of adverse events (AEs), including acute grade 3/4 AEs, which occurred in 75.7% of patients receiving induction chemotherapy and 55.7% of patients in the control arm. Neutropenia, thrombocytopenia, anemia, nausea, and vomiting were the most common grade 3/4 acute AEs associated with induction chemotherapy. Acute side effects were transient and reversible and had minimal impact on patient quality of life. Grade 3/4 late AEs occurred in 9.2% of patients receiving induction chemotherapy and 11.4% of patients receiving standard concurrent chemoradiation.
The investigators concluded that the addition of induction chemotherapy to concurrent chemoradiation results in a clinically meaningful improvement in the survival of patients with locally advanced nasopharyngeal carcinoma. Despite the increase in acute hematologic malignancies, the authors suggested consideration of this treatment approach as a new standard of care.
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