BOSTONDespite substantially increased acute toxicity,
patients with inoperable head and neck tumors benefited from accelerated
radiation therapy in a randomized clinical trial reported by Jean Bourhis, MD,
PhD, at the American Society for Therapeutic Radiology and Oncology (ASTRO)
The local control rate was 58% at 2 years for patients who
received accelerated 62 to 64 Gy radiation therapy in 3 weeks with twice-a-day
dosing. For a comparison group that received standard 70 Gy radiation therapy
in 7 weeks with once-a-day dosing, the rate was 34%.
Dr. Bourhis also reported "a slight increase" in
survival and that, "we are doing a final analysis to determine if this
increase is statistically significant."
Twelve European centers participated in the 268-patient study,
which was conducted by GORTEC (Radiation Oncology Group for Head and Neck
Cancer) between December 1994 and September 1998. Dr. Bourhis is a professor at
the Institut Gustave Roussy, Villejuif, France.
All the patients had locally advanced head and neck squamous
cell carcinoma, most frequently located in the oropharynx (75%); most had T4 (70%) and N2-N3 (65%) disease with poor prognosis
Increase in Acute Toxicity
Patients in the accelerated arm received a median dose of 63 Gy
in 23 days vs 70 Gy in 48 days for the conventional arm. The total dose was 10%
lower for the accelerated patients, who, in turn, were ahead 24% in local
control at 2 years.
The price was a large increase in acute toxicity for the
accelerated group. Not only did 83% of patients have difficulty swallowing with
grade 3-4 mucositis, but 90% required a feeding tube, usually for 6 to 8 weeks.
The accelerated patients were hospitalized more often, Dr. Bourhis said,
although for shorter stays than the control group. In comparison, the patients
receiving conventional therapy had lower rates of grade 3-4 mucositis (28%) and
feeding tube use (41%).
"There was a huge increase in acute toxicity, but so far
we haven’t seen an increase in late effects," Dr. Bourhis reported. He
cautioned that some of the feeding tube use was due not to the radiation
therapy but to the size of the tumors. "Many of the patients had problems
swallowing because of tumor mass," he said. Skin toxicity was about the
same in both groups.
GORTEC plans to continue this research with further studies in
Europe, Dr. Bourhis said. "You can see at 2 years there is a 24%
improvement in locoregional control," he said. "We did see an
improvement that was worthwhile."
Commenting on the study for ASTRO, Lester J. Peters, MD, former
head of the Division of Radiation Oncology, M.D. Anderson Cancer Center,
suggested that future trials should consider newer treatments in the control
"It may be a moot point now to ask whether any form of
altered fractionation is better than a conventional fraction of 2 Gy once a day
up to 70 Gy because this is no longer a standard of care," he said.
"Combined chemoradiotherapy has been shown conclusively to be better than
conventional radiotherapy, as has altered fractionation using either hybrid
fractionation or concomitant boost, so that any further trials must use one of
these preferred methods as the control arm and never 70 Gy in 7 weeks."