Alternating Treatment Regimen Shows Promise in Head and Neck Cancer

Roxanne Nelson

September 15, 2008

September 15, 2008 (Stockholm, Sweden) — Treating locally advanced head and neck cancers with an alternating regimen of chemotherapy and radiotherapy, in addition to cetuximab, has demonstrated promising results, researchers reported here at the 33rd European Society for Medical Oncology Congress. All of the evaluable patients in the cohort experienced a response and, aside from a high rate of localized dermatitis, toxicities were in the range of those generally observed with chemotherapy and radiotherapy in this population.

 

"These results are very promising but they are not controlled," commented Martine Piccart-Gebhart, MD, PhD, professor of oncology at the Université Libre de Bruxelles, in Belgium, and current president of the European Organisation for Research and Treatment of Cancer. "Now we must set up a large trial to prove that these results are valid."

 

Treatment for head and neck cancer has evolved over the past decade and an increasing number of options have emerged. "The treatment of head and neck cancer requires the cooperation of many specialties," said study author Marco Merlano, MD, from the S. Croce General Hospital, in Cuneo, Italy. "We really need a multidisciplinary approach."

 

Combining chemotherapeutic agents, such as platinum, fluorouracil, or cetuximab, with concurrent radiotherapy has shown activity in locally advanced head and neck cancers, but the regimen is associated with excessive toxicity. However, explained Dr. Merlano, treatment with alternating chemotherapy and radiation has demonstrated a toxicity profile that is similar to that of radiation therapy alone.

 

Rapidly alternating chemotherapy and radiotherapy is a variation of concurrent chemoradiation, and in this phase 2 trial, Dr. Merlano and colleagues evaluated the efficacy and toxicity of alternating treatment in 45 patients with squamous cell carcinoma tumors arising from the larynx, oral cavity, oropharynx, and hypopharynx. The majority of patients (84%) had stage 4 disease.

 

Chemotherapy consisted of 20 mg/m2 carboplatin and 200 mg/m2 fluorouracil, administered from day 1 to day 5 on weeks 1, 4, and 7. Radiation therapy consisted of 10 Gy/week in 5 daily fractions on weeks 2–3, 5–6, and 8–10, up to 70 Gy. In addition, cetuximab (Erbitux, ImClone Systems Inc/Bristol-Myers Squibb/Merck KGaA) was added every week during the combination therapy.

 

The researchers assessed patient response to the therapy at 3 months, and 40 patients were available for a full evaluation of response (1 patient refused and it was too early to assess another patient). A complete response was observed in 30 patients, and a partial response in 10 patients. Progression-free survival was more than 21 months and overall survival was more than 23 months in this cohort.

 

The rate of toxicity was fairly high, with 65% experiencing grade 3–4 stomatitis and 29% experiencing grade 3–4 sepsis/pneumonia. There were also a significant number of grade 3–4 hematologic adverse events, and 3 patient deaths were related to toxicity.

 

Although the researchers agree that these adverse events are in line with what can be expected with chemoradiation in head and neck cancer, the large percentage of patients with dermatitis came as a surprise. Grade 3 localized dermatitis was experienced by 32 patients (71% of the cohort), and grade 2 dermatitis was experienced by 11 patients (24%). Only 2 patients (4%) experienced a systemic rash.

 

During a discussion of the study, Carla van Herpen, MD, from Radboud University Nijmegen Medical Center, in Nijmegen, the Netherlands, expressed concern about the high rate of toxic deaths. "Toxic deaths are usually lower in phase 2 trials because the patient population is more selected than in a phase 3 study," she said. "In a phase 3 trial, then, this rate may be evenhigher."

 

33rd European Society of Medical Oncology (ESMO) Congress: Abstract 694PD. Presented September 14, 2008.

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