Researchers affiliated with the EORTC Radiation Oncology Group have reported that patients with operable, advanced squamous cell cancer of the larynx or hypopharynx benefit equally from two different approaches to the delivery of chemotherapy and radiation therapy. The details of this randomized study were published early online in the Journal of the National Cancer Institute on January 17, 2009.

Conventional treatment of patients with advanced, non-metastatic larynx cancer involves removal of the larynx (total laryngectomy). This eliminates the ability of the patient to speak. An advance in the treatment of larynx cancer has been the development of larynx-preserving therapies. Combinations of chemotherapy and radiation therapy, for example, allow some patients to avoid larynx removal without compromising survival.

Sequential therapy is one approach to the delivery of chemotherapy and radiation therapy for larynx cancer. In this approach chemotherapy is given first and patients who respond to this treatment are given additional treatment with radiation therapy. Patients who do not respond are treated with laryngectomy.

A more recent approach is concurrent therapy. In this approach chemotherapy and radiation therapy are given at the same time. This approach appears to result in higher rates of larynx preservation but also has more side effects.

Alternating therapy refers to chemotherapy followed by radiation therapy followed by more chemotherapy, and so on. For example, chemotherapy may be given during weeks 1, 4, 7, and 10, with radiation therapy given during weeks 2-3, 5-6, and 8-9. Researchers hypothesized that this approach to treatment could provide a similar degree of local cancer control as concurrent therapy but with fewer side effects. 

To evaluate alternating therapy, researchers in Europe conducted a Phase III clinical trial among 450 patients with operable, advanced, squamous cell cancer of the larynx or hypopharynx. Half the patients received alternating therapy and half the patients received sequential therapy. Chemotherapy involved cisplatin and 5-FU. In both groups, patients who did not respond to treatment underwent laryngectomy.

Patients have now been followed for over six years. Rates of larynx preservation, overall survival, and progression-free survival did not differ significantly between the two groups. In the sequential group, 30.1% of patients required surgery versus 22.1% in the alternating group. Neck dissections were performed in 34.4% of patients in the sequential group and 24.7% in the alternating group. Laryngectomy was performed in 67 patients in the sequential group and 35 in the alternating group. Functional larynx was achieved in 30.5% of patients in the sequential group and 36.2% in the alternating group. Median progression-free survival was 3.0 years in the sequential group and 3.1 years in the alternating group. Median overall survival was 4.4 years in the sequential group and 5.1 years in the alternating group. 

Acute side effects such as mucositis appeared to be less common among patients treated with alternating therapy than among patients treated with sequential therapy. Grade 3-4 mucositis occurred in 32% in the sequential arm and 21% in the alternating arm.

Comments: These results indicate that sequential and alternating chemotherapy and radiation therapy are similarly effective. However, the trends of the data in terms of a functioning larynx and toxicity favor the alternating therapy approach.

Reference: Lefebvre JL, Rolland F, Tesselaar M et al. Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. Journal of the National Cancer Institute [early online publication]. January 27, 2009.