DOI: 10.1097/01.COT.0000288494.96867.ba
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Issn Print: 0276-2234
Publication Date: 2007/08/10
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Excerpt
As Jean-Louis Lefebvre, MD, Head of the Department of Otolaryngology, Head and Neck Surgery at the Centre Oscar Lambret in Lille, France, explained in his presentation of the latest results, in 1996 the European Organization for Research and Treatment of Cancer (EORTC) Head and Neck Group and Radiotherapy Group initiated a preservation trial comparing sequential induction chemotherapy and radiotherapy versus alternating chemoradiotherapy in resectable cancers of the hypopharynx and larynx.
Patients with untreated, resectable T3-T4 larynx or T2-T3-T4 hypopharynx, N0-N2, M0 squamous cell carcinoma were randomized in this prospective Phase III trial.
Patients in the sequential arm received two conventional cycles of cisplatin/fluorouracil (5-FU) (cisplatin at 100 mg/m2 on Day 1, 5-FU at 1,000 mg/m2 on Days 1–5). If they responded, this was followed by two additional cycles of chemotherapy, followed on Day 80 by 70 Gy of radiotherapy in 35 fractions over seven weeks.
In the alternating arm, a chemotherapy cycle in Weeks 1, 4, 7, and 10 was alternated with radiotherapy consisting of 20 Gy in 10 fractions during the three two-week intervals for a total radiotherapy dose of 60 Gy. Patients had surgery and postoperative chemoradiotherapy in case they didn't have a response.
The primary endpoint was survival with a functional larynx, with events including local relapse, laryngectomy, tracheotomy, gastrostomy, feeding tube, and death. The trial enrolled 450 patients, 224 to the sequential arm and 226 to the alternating arm from July 1996 to May 2004.
The two groups were well balanced, with a median age of 55. Half the patients had hypopharynx cancer, one-third had supraglottis cancer, and about one-seventh had glottis/transglottis cancer. The majority of patients had T3 or T4 disease. One third had no palpable lymph nodes and no clinical metastatic lymph nodes. The vast majority of patients had Stage III or IV.
“In nearly 30% of the patients, we had to interrupt treatment, mainly due to toxicity in the alternating arm,” Dr. Lefebvre said.
Most of the patients in both groups had the planned dose of cisplatin. “We had to reduce 5-FU in the sequential arm more often than in the alternating arm, mainly due to mucosal toxicity,” he said. The reasons for dose modifications were mainly hematologic toxicity in the alternating arm and mucosal toxicity in the sequential arm, due to the dose of 5-FU.
“In the alternating arm we had to delay radiation from time to time due to toxicity induced by chemotherapy in between cycles of irradiation,” Dr. Lefebvre said. “There were only a few permanent discontinuations due to irradiation in each arm.
