Clinical Trial: Concurrent Chemoradiation Versus Surgery With Adjuvant Therapy in Advanced Laryngopharyngeal Cancers

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Phase III Randomized Clinical Trial to Compare Results of Concurrent Chemo-radiation With Surgery and Postoperative Radiotherapy/Chemoradiotherapy in Advanced Laryngeal and Hypopharyngeal Cancers

Brief Summary:

Surgery with post operative radiotherapy (PORT) had been the mainstay of treatment for advanced laryngeal-pharyngeal cancers (ALHC) until the eighth decade of the past century. Total laryngectomy with post-operative radiotherapy (TL + PORT) used to result in permanent tracheostomy and loss of speech.

Early trials like the VA or European Organisation for Research and Treatment of Cancer (EORTC) trials compared surgery with post-operative radiotherapy to induction chemotherapy (ICT) and radiotherapy (RT). Subsequent attempts have been focused on the added benefit of including concurrent chemotherapy. There is no randomized trial available in the literature comparing concurrent chemoradiation with the standard treatment, i.e. surgery followed by radiotherapy. However, most of the studies comparing neoadjuvant chemotherapy and radiotherapy reported better locoregional control rates and better survival rates with surgery followed by post-operative chemotherapy. Further, the advances in primary voice rehabilitation have substantially improved the quality of life after laryngectomy. Thus, there is a strong case for comparing the results of concurrent chemo-radiation with surgery and post-operative radiotherapy in a randomized clinical trial. This trial will answer the question - "whether we are saving voice at the cost of life".

The investigators propose to randomize 900 patients of laryngeal and hypopharyngeal cancers in surgery with PORT and a concomitant chemoradiation arm and compare the survival and locoregional control rates.


Detailed Summary:

TL + PORT has traditionally been the gold standard in management of ALHC. However, this results in permanent tracheostomy and a possible loss of speech. In case of partial laryngectomy and even in case of TL, there are various options of voice rehabilitation but the successes of all these procedures are highly variable. In 1980s several authors reported interesting possibility of LP with ICT. The first randomized study (RCT) came from VA group who randomized patients to receive either 2 cycles of ICT + RT Vs surgery +PORT. Patients with more than PR received a 3rd cycle followed by definitive RT. There were more local recurrences and fewer distant metastases in the ICT arm. Of the 166 ICT patients, nearly 1/3rd required salvage TL with ultimate LP in 66% surviving patients. These results proved that ICT and definitive RT can be effective in LP without compromising overall survival. European Organization for Research and Treatment of Cancer (EORTC) study randomly assigned hypopharynx cancer patients to receive either immediate surgery with PORT (arm 1) or ICT. Patients with a CR after 2 or 3 cycles of CT were treated there after by RT. Locoregional failures occurred at approximately the same frequencies in both arms but there were fewer distant failures in the ICT arm. The median survival was found to be similar in both arms with LPR of 35% in the ICT arm. This study showed the feasibility of LP in patients with cancer of the hypopharynx. A smaller trial from MSKCC15 reported 52% LPR and another European RCT reported poorer survival in the CT arm with LPR of 20% only. The latter trial had a smaller number of patients and imbalance in randomized groups (4 out of 5 stage IV patients got randomized into CT arm) that could have flawed the outcome. The 3 RCTs (excluding MSKCC trial) were compiled by MACH-NC to obtain a meta analysis that showed similar disease free survival and a non significant trend of higher 6% survival in
Sponsor: Tata Memorial Hospital

Current Primary Outcome:

  • Overall survival at 3 and 5 years [ Time Frame: 2015 ]
  • Disease free survival at 3 and 5 years [ Time Frame: 2015 ]
  • Locoregional control rates at 3 and 5 years [ Time Frame: 2015 ]


Original Primary Outcome:

  • Overall survival at 3 and 5 years
  • Disease free survival at 3 and 5 years
  • Locoregional control rates at 3 and 5 years


Current Secondary Outcome:

  • Patterns of relapse [ Time Frame: 2015 ]
  • Salvage rates [ Time Frame: 2015 ]
  • Treatment-related adverse events [ Time Frame: 2015 ]
  • Completion of treatment [ Time Frame: 2015 ]
  • Quality of life [ Time Frame: 2015 ]


Original Secondary Outcome:

  • Patterns of relapse
  • Salvage rates
  • Treatment-related adverse events
  • Completion of treatment
  • Quality of life


Information By: Tata Memorial Hospital

Dates:
Date Received: August 9, 2005
Date Started: May 2005
Date Completion: May 2015
Last Updated: January 21, 2013
Last Verified: January 2013