• 12/2/2004
  • Laurie Barclay, MD
  • Medscape (www.medscape.com)

Four cycles of neoadjuvant chemotherapy is a promising approach for treating patients with inoperable advanced head and neck squamous cell carcinoma (HNSCC), according to follow-up data from a 10-year randomized trial published in the Nov. 17 issue of the Journal of the National Cancer Institute.

“Chemoradiotherapy is the standard treatment for locally advanced HNSCC; the standard treatment for patients with operable HNSCC is surgery followed by postoperative radiotherapy, with or without adjuvant chemotherapy,” write Pier Luigi Zorat, from Ospedale Ca’ Foncello in Treviso, Italy, and colleagues. “Although neoadjuvant chemotherapy has a proven role in organ preservation and statistically significantly reduces the incidence of distant metastases, especially in laryngeal and hypopharyngeal cancers, its efficacy in prolonging overall survival has not yet been demonstrated.”

The investigators compared induction chemotherapy with cisplatin and 5-fluorouracil followed by locoregional treatment (surgery and radiotherapy or radiotherapy alone) with locoregional treatment alone in patients with HNSCC. In this multicenter trial, 237 patients with nonmetastatic stage III or IV HNSCC were randomized to receive four cycles of neoadjuvant chemotherapy followed by locoregional treatment (group A) or locoregional treatment alone (group B).

In group A, overall survival at five and 10 years was 23% (95% confidence interval [CI], 15.3% – 30.9%) and 19% (95% CI, 11.6% – 26.4%). In group B, the corresponding survival rates were 16% (95% CI, 9.6% – 23.4%) and 9% (95% CI, 3.5% – 14.7%; P = .13).

For operable patients, there was no difference between group A and group B in overall survival at five and 10 years (group A, 31% [95% CI, 14.9% – 47.3%] and 22.7% [95% CI, 7.1% – 38.3%], respectively; group B, 43.3% [95% CI, 25.6% – 61.0%] and 14.2% [95% CI, 0.1% – 28.3%], respectively; P = .73).

For inoperable patients, overall survival at five and 10 years was 21% (95% CI, 12.3% – 30.1%; and 16% (95% CI, 7.7% – 23.9%), respectively, for group A and 8% (95% CI, 1.5% – 12.3%) and 6% (95% CI, 0.1% – 9.1%), respectively, for group B (P = .04).

A potential limitation of this study is the use of locoregional treatment as the reference group for inoperable patients.

“Four cycles of neoadjuvant chemotherapy is a promising approach for treating patients with inoperable advanced head and neck cancer but not for treating patients with operable disease,” the authors write. “The advent of new active drugs, such as taxanes, makes questions about the utility of neoadjuvant chemotherapy more interesting. On the basis of our feasibility data, an Italian multicenter phase III trial has been initiated that is testing the efficacy of concomitant chemotherapy and radiotherapy (i.e., two cycles of polychemotherapy with cisplatin–5-fluorouracil during radiotherapy) with or without three cycles of neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil.”

In an accompanying editorial, Arlene A. Forastiere, MD, from The Johns Hopkins University in Baltimore, Maryland, notes that for intermediate stage disease, the toxicity of neoadjuvant therapy most likely outweighs potential benefits. Upcoming trials should define the role of induction chemotherapy in advanced disease and will therefore have the potential to redefine the current standard of care.

“The majority of deaths from locally advanced head and neck cancer are due to complications of uncontrolled locoregional disease, and this pattern of failure must be altered to improve patient survival,” Dr. Forastiere writes. “Although the ‘best’ combined-modality approach remains controversial, chemotherapy clearly has a major role in the management of most patients with advanced head and neck cancer.”

Source:
J Natl Cancer Inst. 2004;96(22):1647-1649, 1714-1717