Comparison of TPF Induction and CCRT with CCRT alone

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Several phase 3 trials were conducted between 2015 and 2017:
    • Which directly compared taxane-based induction chemotherapy (IC) with concurrent chemoradiation (CCRT):
      • On groups of unselected locally advanced head and neck cancer (LAHNC):
        • Most of IC protocols were followed by CCRT:
          • But one trial had RT combined by targeted therapy
  • The first of this list includes the multi-center PARADIGM trial:
    • That considered high-risk patients with high nodal load
    • A hundred and forty-five patients were randomized to either be treated with CCRT with 2 cycles of 100 mg/m2 cisplatin or 3 cycles of TPF followed by CCRT with weekly carboplatin for good responders or weekly docetaxel for the rest
    • No significant differences in progression free survival (PFS) or overall survival (OS) were detected between groups
    • Unexpectedly, both groups were advantaged with good survival results:
      • 3 year overall survival (OS) 73% (95% CI 60–86) in IC, vs. 78% (66−86) in CCRT (Haddad et al., 2013)
  • A second trial, DeCide:
    • Used CCRT in both arms with 2 cycles of induction with TPF in the experimental arm
    • Here, 285 patients were recruited and randomized
    • Cancer deaths and distant metastases were reduced with induction:
      • But serious adverse events and non-cancer related deaths increased
    • As well, none of the survival measures improved with IC
    • Similar to the PARADIGM trial:
      • Mean OS was higher than predicted in both groups, and patients were prescribed with an unconventional regimen (including fluorouracil, docetaxel, and hydroxyurea)
    • Moreover, both mentioned trials were disadvantaged for being underpowered:
      • 200 were planned for PARADIGM and 400 for DeCide (Cohen et al., 2014)
  • The 3-armed Spanish TTCC trial:
    • Was the first well-designed study to compare:
      • TPF-CCRT, PF-CCRT, and CCRT, with standard high-dose cisplatin combined with RT
    • The trial reached its accrual goals and 439 patients were analyzed
    • The results did show a trend of higher PFS, in favor of induction over CCRT:
      • But only as a result of per-protocol analysis:
        • In fact 27% of patients in the TPF arm did not receive the treatment as scheduled:
          • Likewise, intention to treat analysis showed no PFS advantage in any group (logrank P = 0.56) (Hitt et al., 2014)
          • Moreover, in a follow-up study, OS, PFS, and TTF were neither significantly different when intention to treat analysis compared TPF followed by CCRT with CCRT alone (Hitt et al., 2021 Apr)
  • The GORTEC 2007–02 trial:
    • Examined TPF induction followed by cetuximab with RT in comparison to CCRT with 3 cycles of carboplatin and fluorouracil on 370 LAHNC patients
    • Similar to DeCide, there was a decrease in distant metastases in the TPF arm:
      • Though the documented response rate was poor (45%), and both PFS and OS were almost identical in the two groups
    • Nevertheless, the concerning effect was that the rate of early deaths was as high as 6.6% (Geoffrois et al., 2016)
  • The Italian GSTTC:
    • A primarily phase 2 (and 3) study with a 2 × 2 factorial design:
      • Evaluated CCRT with cisplatin (cumulative dose of 160 mg/m2) and 5-FU (800 mg/m2/ 96 h) or cetuximab with or without a modified TPF (docetaxel 75 and cisplatin 80 mg/m2 day 1 and 5-fluorouracil 800 mg/m2/day 96-h) induction
      • Among 414 patents over half were oropharyngeal cases, and most patients had excellent performances (79% ECOG 0 and the rest 1)
      • Outcomes were far better with IC with a median OS of 54.7 vs. 31.7 months in favor of IC and a significantly higher PFS (median 29.7 months vs. 18.5, HR 0.72; 95% CI 0.56–0.93; p = 0.013) and OS (HR 0.74; 95% CI 0.56–0.97; p = 0.031)
      • The results of TPF followed by CCRT versus CCRT alone:
        • Was not significantly different:
          • While the comparison of TPF followed by cetuximab and RT showed to be superior to cetuximab and RT alone
      • Furthermore, compliance with IC was high, as 93% of patients were able to receive the planned 3 cycles of TPF, and early deaths were 1%
      • This was a unique trial that showed OS benefit for IC but likely because of the good prognose of the subjects
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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