Background
Phase III randomized trial (DeCIDE). N=285 (planned 300; closed early for slow accrual), untreated non-metastatic N2 or N3 SCC of the head and neck (any primary). 17 US institutions, 2004–2009. Hypothesis: induction chemotherapy (IC) before CRT improves OS by reducing distant failure in high nodal-burden patients. Stratified by primary site, N2 vs N3, and center.
Interventions and follow up
Arm A: Induction docetaxel 75 mg/m² D1 + cisplatin 75 mg/m² D1 + fluorouracil 750 mg/m²/day D1–5 (TPF) × 2 cycles → CRT (docetaxel + fluorouracil + hydroxyurea + RT 0.15 Gy BID every other week, 75 Gy)
Arm B: CRT alone (same CRT regimen, 75 Gy)
Primary endpoint: OS
mFollow up: 30 months minimum
Arm B: CRT alone (same CRT regimen, 75 Gy)
Primary endpoint: OS
mFollow up: 30 months minimum
Results
OS: HR 0.91 (95% CI 0.59–1.41) — not significant
RFS: not significantly different
Distant failure-free survival: not significantly different
Distant failure rate: numerically lower with IC (10% vs 19%, P=.025) — no OS translation
RFS: not significantly different
Distant failure-free survival: not significantly different
Distant failure rate: numerically lower with IC (10% vs 19%, P=.025) — no OS translation
Adverse events
Induction (IC arm) grade 3–4: febrile neutropenia 11%, mucositis 9%
CRT phase (both arms) grade 3–4: mucositis 49%, dermatitis 21%, leukopenia 18%
Serious AEs during CRT: more common in IC arm (47% vs 28%, P=.002)
CRT phase (both arms) grade 3–4: mucositis 49%, dermatitis 21%, leukopenia 18%
Serious AEs during CRT: more common in IC arm (47% vs 28%, P=.002)
Conclusions
Induction TPF before CRT did not improve OS, RFS, or distant failure-free survival vs CRT alone in N2/N3 HNSCC. The trial was underpowered due to failure to reach planned accrual and unexpectedly high survival in both arms. IC cannot be routinely recommended based on this trial.
Key Limitations
Significantly underpowered (285 vs planned 300+) — halted for slow accrual, powered only for very large effects. OS better than predicted in both arms, suggesting a favorable population. The CRT regimen (hydroxyurea-based q2wk split-course) is non-standard. HPV status not analyzed prospectively. Published alongside PARADIGM, reinforcing the same conclusion with two underpowered trials.
Clinical Context
DeCIDE and PARADIGM (2013–2014) are two negative phase III trials that largely ended enthusiasm for routine induction TPF before CRT in LA-HNSCC. TAX 323/324 established induction TPF before RT as better than PF-induction, but adding IC before CRT has never shown OS benefit. ASCO and ESMO do not recommend routine IC before CRT; it is reserved for selected cases (imminent airway compromise, organ-preservation need, or high distant-failure risk).