Long-Term Results of RTOG 91-11: A Comparison of Three Nonsurgical Treatment Strategies to Preserve the Larynx in Patients With Locally Advanced Larynx Cancer
- Study type
- Clinical trial
- Study name
- RTOG 91-11
- Design
- Three-arm randomised (Intergroup) trial comparing larynx-preservation strategies
- Sample size
- 520 patients (analysed)
- Source
- JCO · 2013
In plain words
This study compared three non-surgical treatments for people with advanced cancer of the larynx (voice box), aiming to keep the larynx: chemotherapy before radiotherapy, cisplatin chemotherapy given at the same time as radiotherapy, and radiotherapy alone. After about 10 years of follow-up, both approaches that included chemotherapy increased the chance of being alive without removal of the larynx compared with radiotherapy alone. Giving cisplatin and radiotherapy together helped keep the larynx more than the other two approaches, but in this group there were more deaths from causes not related to the larynx cancer or its treatment. The choice of treatment should be made with the care team, based on each patient's situation.
Key results
Treatment arms and regimens
Up to 3 cycles of PF every 3 weeks: cisplatin 100 mg/m² on day 1 and fluorouracil 1000 mg/m² per day for 5 days. Responders (at least 50% reduction of the primary tumour and at least stable disease in the neck) received radiotherapy 70 Gy in 35 fractions (2 Gy per fraction). Patients with less than a partial response at the primary site after 2 cycles of PF, progression in the neck, or progression at any time during induction underwent salvage surgery (laryngectomy).
Cisplatin 100 mg/m² on days 1, 22 and 43 of radiotherapy, concurrently with radiotherapy to 70 Gy.
Radiotherapy alone to 70 Gy, without chemotherapy.
Source of the regimen details: Full text of the paper (PMC3577950)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
547 patients randomised (520 analysable: 174 induction, 174 concurrent and 172 radiotherapy alone) with stage III or IV squamous cell carcinoma of the glottic or supraglottic larynx treatable by laryngectomy and radiotherapy; T1 and large-volume T4 tumours (more than 1 cm invasion of the base of tongue or cartilage penetration) were excluded. Distribution: T2 11%, T3 79% and T4 10%; N0 50%, N1 21%, N2 28% and N3 2%; 64% stage III. Planned neck dissection was recommended for patients who were N2 or N3 at initial staging.
Endpoints
Primary endpoint: laryngectomy-free survival (LFS), a composite endpoint. Other endpoints reported in the abstract: overall survival, larynx preservation rate, locoregional control and late adverse events.
Safety and side effects
10-year cumulative incidence of grade 3 to 5 late adverse events: 30.6% (induction), 33.3% (concurrent) and 38% (radiotherapy alone), with no significant difference between groups; however, deaths not related to the larynx cancer or treatment were more frequent in the concurrent chemotherapy group (30.8% versus 20.8% with induction chemotherapy and 16.9% with radiotherapy alone). In the initial report of the same trial (Forastiere et al, NEJM 2003), severe adverse events were more frequent in the chemotherapy groups (81% with PF induction followed by radiotherapy and 82% with concurrent cisplatin, versus 61% with radiotherapy alone), and mucosal toxicity during radiotherapy with concurrent cisplatin was almost twice that of the other two groups.
Clinical significance and place in guidelines
Based on the abstract, concurrent cisplatin with radiotherapy improved the larynx preservation rate and locoregional control compared with PF induction chemotherapy followed by radiotherapy and compared with radiotherapy alone. Overall survival did not differ significantly, and non-cancer deaths were more frequent in the concurrent arm. The authors stress the need for new strategies with less toxicity. The status of these results in current guidelines should be checked separately, as the abstract gives no information on it.
Limitations
Based on the abstract, the increase in deaths not related to the larynx cancer or treatment in the concurrent chemotherapy group and the possibility of worse overall survival (not significant) should be interpreted with caution. The authors raise the need for less toxic approaches. The confidence interval reported for the comparison of concurrent therapy with radiotherapy alone (0.78 to 0.98) is given exactly as in the published abstract.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.