Preliminary results fo the GORTEC 96-01 randomized trail, comparing very accelerated radiotherapy versus concomitant radio-chemotherapy for locally inoperable HNSCC

Reviewer: Mary Kara Bucci, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 22, 2002

Presenter: J. Bourhis
Presenter's Affiliation: Institute Goustave-Roussy, Villejuif, France
Type of Session: Scientific

Background

Recent evidence demonstrates improved outcome in squamous cell carcinoma of the head and neck(HNSCC) with altered fractionation radiation (RT) or concurrent chemoradiotherapy (CRT). There have been few direct comparisons between these 2 modalities. This randomized trial for inoperable HNSCC compares one CRT regimen with accelerated RT.

Materials and Methods

109 patients were randomized to accelerated RT, 62-64 Gy/3weeks, or CRT with cisplatin and 5 FU and 62-64 Gy/5 weeks.
In arm 1 (RT), pts received 2 Gy twice daily for 3 weeks. In arm 2, pts received 2 Gy twice daily (bid)for one week, then had one week of no treatment, then another week of 2 Gy bid, followed by one more week of rest and a final week of 2 Gy bid, for a total of 62-64 Gy /5 weeks. Cisplatin 100 mg/m2 was given on days 1, 16 and 32, and 5FU 1000mg/m2 was given by 96 hour infusion on days 1-5 and 31-35. All patients who were able received 2 further cycles of 5FU/cisplatin, 28 days and 56 days after the final fraction of RT.
Eligible patients had inoperable disease, with 90% of pts having N3 nodal involvment (mean lymph node diameter, 8 cm).

Results

Grade 3-4 mucosal toxicity was experienced by 96% of pts in the RT arm, and 81% in the CRT arm. 92% (RT) and 94% (CRT) of pts required a PEG tube for nutrition support.
In the CRT arm, 10% of pts had grade 4 WBC toxicity, and 4% had grade 2 ro higher renal toxicity.
47% of pts on the CRT arm received all planned chemotherapy.
There were 9 deaths within 3 months of treatment in the CRT arm, and 2 in the RT arm. Causes of death included: septic (2), vacular (2), pulmonary (3), unknown (1).
53% (RT) and 36% (CRT) of pts had a distant metastasis as a first event (p=NS).
42% (RT) and 31% (CRT) had a local/regional failure as a first event (p=NS).
Overall survival was 24% (RT) and 21% (CRT), p=NS.
This study was closed early due to the increased number of treatment-related deaths.

Author's Conclusions

The 5FU/cisplatin regimen used in this study was poorly tolerated, with an increased number of treatment related deaths.
There was no significant benefit in OS, DFS, or LRC.
New treatment approaches are needed in this poor-prognosis group of inoperable HNSCC.

Clinical/Scientific Implications

This trial shows that the CRT scheme used here was not tolerable, and the trial closed early. Both arms of this trial used altered fractionation radiation. The terms "altered fractionation" "accelerated fractionation" and "hyperfractionation" can mean different specific regimens in different studies; 2 Gy bid for 62-64 Gy/3 weeks is a faster, or more accelerated, delivery of radiation than that used in other trials of "accelerated" RT. The regimen used in this study, 62-64 Gy/3weeks, is based on a trial from the same group presented at ASCO 2000, which showed improved LRC and increased but manageable toxicity. GORTEC is currently running a three arm trial of conventional, once daily RT (70 Gy /7 weeks) with concurrent chemotherapy (5FU plus carboplatin), vs accelerated RT (70 Gy/6 weeks) with chemotherapy, vs acclerated RT (64.8 Gy/3.6 weeks) alone. This 3 arm study also addresses the question of the superiority of CRT vs RT alone, with 2 different fractionation schemes in the CRT arms.

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