Sequential chemotherapy for the curative treatment of squamous cell cancer of the head and neck: A new paradigm

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Abstract

The integration of chemotherapy into the combined modality treatment of squamous cell cancer of the head and neck (SCCHN) has remained controversial. There is compelling evidence from clinical trials and meta-analyses that chemotherapy increases survival and reduces morbidity by organ preservation. There are two distinct methods of delivering chemotherapy as part of the curative treatment for locally advanced disease - induction chemotherapy and chemoradiotherapy - and both are effective. Induction chemotherapy improves patient performance before definitive radiotherapy, allows high systemic exposure of chemotherapy, and permits intermediate assessment of prognosis and adjustment of subsequent therapy. Induction chemotherapy does not increase local/regional dose intensity and many failures are local/regional. Chemoradiotherapy increases local/regional dose intensity and increases local/regional control, but chemoradiotherapy regimens are associated with significant short- and long-term local/regional toxicity and poor long-term survival. Surgery, timed to be most effective after chemotherapy and radiotherapy, can eliminate some sites of bulk disease or persistent tumors. Addition of taxanes (T) to the standard therapy, cisplatinum/5-fluorouracil (PF), may increase the effectiveness of induction chemotherapy. Phase II trials of docetaxel in combination with PF or PF plus leucovorin (L), TPF, and TPFL, respectively, have demonstrated significant response rates and long-term survival of patients with advanced disease. TPF, an intermediate-dose regimen, with toxicity comparable to PF, has entered phase III testing to compare it with standard PF. The design of the North American phase III trial of TPF vs PF, TAX 324, incorporates a new paradigm for treatment of locally advanced SCCHN-sequential chemotherapy. In TAX 324, sequential chemotherapy includes intensive induction chemotherapy, chemoradiotherapy with weekly carboplatinum, and planned surgery as the final stage. Two additional studies of sequential chemotherapy are being performed or have been completed. While TAX 324 includes carboplatinum in its chemoradiotherapy phase, other sequential chemotherapy plans either have more intensive chemoradiotherapy or are targeted at patients who have a poor prognosis after induction chemotherapy. Sequential chemotherapy places induction chemotherapy and chemoradiotherapy into an integrated treatment plan and offers advantages over both forms of single treatment. Future studies may target more or less intensive chemoradiotherapy for patients with different prognoses and thus limit short-term toxicity and long-term morbidity.

Original languageEnglish
Pages (from-to)193-202
Number of pages10
JournalOncology Spectrums
Volume2
Issue number3
StatePublished - 2001
Externally publishedYes

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