TPF sequential therapy: when and for whom?

Concurrent chemoradiation is a standard approach for the treatment of locally advanced squamous cell carcinoma of the head and neck. However, sequentially administered chemotherapy and radiotherapy/chemoradiation may be an effective alternative for some patients. Although chemoradiation is a highly effective treatment approach, it is associated with high incidences of severe acute toxicities, including mucositis. In addition, late toxicities can cause long-term morbidity in a substantial proportion of patients. In a retrospective analysis of three Radiation Therapy Oncology Group trials, pharyngeal dysfunction was seen in 27% of patients and feeding tube dependence and laryngeal dysfunction were each seen in approximately 12% of patients. Sequential administration of chemotherapy and radiotherapy, with a doublet cisplatin and 5-fluorouracil (PF) induction chemotherapy regimen, is associated with less acute severe mucositis than concomitantly administered cisplatin and radiotherapy. The addition of the taxane docetaxel to PF has resulted in the highly active triplet induction regimen TPF. Data from randomized trials indicate that TPF sequential therapy may be an effective alternative to concurrent chemoradiation for some patients. TPF is well tolerated, although it is associated with a higher incidence of hematologic adverse events than with PF, including neutropenia and neutropenia-related complications. This may be managed by the use of prophylactic G-CSF and/or antibiotics. Patients suitable for treatment with a TPF-based sequential administration approach include those with a good performance status, no contraindication to cisplatin or taxanes, and locally advanced oropharyngeal, hypopharyngeal, or laryngeal cancer with a high tumor load.