First Generation Laryngeal Carcinoma Preservation Trials

The first generation of larynx preservation chemotherapy trials:
- Appeared in the 1990s:
  - They randomized patients into surgery and radiotherapy or to induction chemotherapy cycles of cisplatin / 5FU:
    - Patients who responded to chemotherapy then received radiotherapy:
      - With possible salvage surgery
  - If they did not respond to the chemotherapy:
    - They received surgery and postoperative radiotherapy
- Generally, the results of these studies showed:
  - No significant difference in survival:
    - Between the two treatment arms
- The larynx was preserved in:
  - 56% of patients undergoing the experimental chemoradiotherapy arm
In 2000, Pignon et al:
- Published a meta-analysis of the first generation of laryngeal preservation chemoradiotherapy trials:
  - In the main, they included T3 laryngeal and hypopharyngeal cancers
- There was no statistically significant difference in overall survival:
  - However, it is important to note:
    - That there was a trend to benefit from surgery:
      - Hazard ratio 1.19 intervals (0.97–1.46)
    - Surgery ± radiotherapy:
      - Resulted in overall survival of 45%:
        
        Compared to an overall survival from chemoradiotherapy of:
        
        39%
    - 56% of those who survived with chemoradiotherapy:
      - Managed to avoid laryngectomy:
        
        Giving an overall laryngectomy survival rate of:
        
        23% at five years
    - Patients treated with chemoradiotherapy:
      - Had almost double the local recurrence rate:
        
        But less distant metastases than the patients treated with surgery
    - Analysis of laryngeal cancer patients separately from hypopharyngeal cancer patients:
      - Showed that laryngeal cancer patients in the surgical arm:
        
        Demonstrated a risk reduction of 32%:
        
        This suggests that advanced laryngeal tumors would be better treated with surgery than chemoradiotherapy:
        
        On the other hand, hypopharyngeal cancer patients showed no difference in survival between the two modalities of treatment
The meta-analysis showed that the overall survival benefit from chemotherapy in addition to radiotherapy:
- Was 4% at five years
Concomitant chemotherapy:
- Resulted in an 8% overall survival benefit:
  - Compared to a 4% overall survival benefit from neoadjuvant chemoradiotherapy
Adjuvant chemoradiotherapy:
- Resulted in no overall survival benefit
These findings have resulted in the adoption of concomitant chemoradiotherapy as the standard regimen for delivery of chemotherapy when treating laryngeal and pharyngeal cancers:
- Recently, an update of this meta-analysis confirmed an overall survival effect of 6.5% for concomitant chemoradiotherapy
References:
- The Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. New England Journal of Medicine 1991; 324: 1685–90.
- Pignon JP, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 2000; 355: 949–55.
- Pignon JP, le Maítre A, Maillard E et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiotherapy and Oncology 2009; 92: 4–14.
- Forastiere AA, Goepfert H, Maor M et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. New England Journal of Medicine 2003; 349: 2091–8.