LISBON, Portugal-For patients with locally advanced head and neck cancer, coupling cisplatin (Platinol) with radiotherapy leads to longer survival and fewer recurrences than does radiation alone, according to the first results of EORTC study 22931.
LISBON, PortugalFor patients with locally advanced head and neck cancer, coupling cisplatin (Platinol) with radiotherapy leads to longer survival and fewer recurrences than does radiation alone, according to the first results of EORTC study 22931.
This randomized phase III trial was jointly conducted by the Head and Neck and Radiotherapy groups of the European Organization for Research and Treatment of Cancer (EORTC).
Jacques Bernier, MD, of the Oncology Institute of Southern Switzerland, Bellinzona, presented the results at the 11th European Cancer Conference (ECCO abstract 989). He said that EORTC investigators from 23 centers in 12 countries enrolled 334 patients with cancer of the oral cavity, oropharynx, hypopharynx, or larynx.
Eligible patients had stage T3-T4 disease, or T1-T2 disease with two to three positive nodes and no metastases, or T1-T2 disease with fewer than two positive nodes plus a high risk factor, such as perineural involvement. "Importantly, two thirds of patients were stage T3-T4," Dr. Bernier said.
After undergoing primary surgery performed with curative intent, study participants were randomized to receive either radiotherapy alone, consisting of 66 Gy given in 33 fractions over 6.5 weeks, or the same radiation schedule paired with cisplatin 100 mg/m² on days 1, 22, and 43. Dr. Bernier pointed out that two thirds of surgical procedures achieved tumor-free margins.
Although patients treated with cisplatin experienced significantly more functional mucosal reactions, they showed no significant excess of objective mucosal reactions.
Cisplatin was responsible for grade 3-4 leukopenia in 14% of patients, grade 3-4 granulocytopenia in 11%, grade 3-4 thrombocytopenia in 2%, grade 3-4 nausea in 11%, and grade 3-4 vomiting in 10%. Notwithstanding these side effects, two thirds of patients completed two of the planned three cycles of chemotherapy, and half completed all three cycles.
Disease-free survival after a median follow-up of 34 months was markedly superior among patients assigned to concurrent radiotherapy and chemotherapy (59% vs 41% with radiation alone, P = .0096). Likewise, Dr. Bernier said, the difference in overall survival favored combined-modality therapy (65% vs 49%, P = .0057).
"The pattern was the same for time to progressionat 3 years we have a difference of 22% between the two arms, with a P value of .0016," Dr. Bernier said. "As expected from the data generated for the survival endpoints, we have a striking difference in terms of locoregional control, with estimates of 83% and 64%, respectively (P = .0014)."
No differences between the two treatment approaches have yet emerged for the incidence of second primary tumors or the effects of therapy on normal tissue. "We have to wait for longer follow-up to be able to assess accurately these particular endpoints," Dr. Bernier said.
As to the incidence of distant metastases, at 3 years there is a difference of 9%, "which, so far, is not significant, but we shall certainly monitor this endpoint very closely in the next months," he said.
Dr. Bernier concluded: "This study shows that, as compared to radiation therapy, the combination of radiation with high-dose cisplatin yields not only a significantly higher rate of local control but also significantly better disease-free and overall survival rates, which is rather rare in head and neck oncology."