Chemotherapy advances in locally advanced head and neck cancer

Table 1 DeCIDE and PARADIGM Protocols

	DeCIDE	PARADIGM
Stages	IV	III, IV
Arm 1 (standard)	CRT CRT: five 14 d cycles of docetaxel (day 1), fluorouracil (day 0-4) and hydroxyurea (day 0-4) with twice daily radiation (day 1-5)	CRT cisplatin (100 mg/m2) Q 3 wk, 12 cycles Radiation: accelerated concomitant boost over 6 wk (72 Gy)
Arm 2 (experimental, induction)	TPF (2) → CRT TPF two cycles: docetaxel 75 mg/m2 day 1, cisplatin 100 mg /m2 day 1, fluorouracil 1000 mg/m per day continuous for 5 d CRT: five 14 d cycles of docetaxel (day 1), fluorouracil (day 0-4) and hydroxyurea (day 0-4) with twice daily radiation (day 1-5)	TPF (3) → CRT TPF three cycles: docetaxel 75 mg/m21, cisplatin 100 mg/m2 day1, fluorouracil 1000 mg/m2 continuous for 4 d Responders to induction: CRT (carboplatin AUC 1.5, weekly) Poor responders to induction CRT (docetaxel 20 mg/m2 weekly) Radiation: accelerated concomitant boost over 6 wk (72 Gy) for poor responders. Induction chemotherapy responders 70 Gy over 7 wk

¹Statistically significant. CRT: Chemoradiation.

Table 2 DeCIDE and PARADIGM results

Study	Patients	Randomization (induction regimens)	PFS (3 yr)	OS (3 yr)	DM
PARADIGM	145	CRT	69%	78%	11%
		TPF (3) → CRT	67%	73%	7%
DeCIDE	280	CRT	59%	73%	19%1
		TPF (2) → CRT	67%	75%	10%1

¹Statistically significant. CRT: Chemoradiation; DM: Distant metastasis.

Table 3 Tax 323 and 324 results

Study	Patients	Randomization (induction regimens)	PFS (mo)	OS (mo)	DM (%)
Tax 323	358	PF	8.21	14.51	10.3
		TPF	111	18.81	12.9
Tax 324	501	PF	131	301	9
		TPF	361	711	5

¹Statistically significant. PFS: Progression free survival; OS: Overall survival; DM: Distant metastasis.

Table 4 Tax 323 and 324 Protocols

	Tax 323 study	Tax 324 Study
Stages	III, IV	III, IV
Induction therapy regimens	TPF: docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, fluorouracil infusion 750 mg/m2 per day continuous infusion day 1 to 5	TPF: docetaxel 75 mg/m2 day 1, cisplatin 100 mg/m2 day 1, fluorouracil 1000 mg/m2 per day, continuous 24 h IV infusion for 4 d
	PF: cisplatin 100 mg/m2 day 1, fluorouracil 1000 mg/m2 continuous infusion days 1 to 5	PF: cisplatin 100 mg/m2 day 1, fluorouracil 1000 mg/m2 per 24 h continuous infusion for 5 d
Concurrent therapy regimens	Start 4-7 wk after completing induction therapy:	Start 3-8 wk after completing induction therapy:
	Radiation administered over 7 wk, either conventional (66 to 70 Gy), accelerated (70 Gy) or hyperfractionated (74 Gy)	Radiation 2 Gy per day, 5 d a week for a total of 70-74 Gy plus weekly carboplatin AUC 1.5

Gy: Gray; TPF: Docetaxel, cisplatin, and fluorouracil; PF: Cisplatin and fluorouracil.

Table 5 Concurrent regimens after induction

Study	Concurrent chemotherapy	Radiation	Notes
Tax 323	None	Conventional (66 to 70 Gy), accelerated (70 Gy) or hyperfractionated (74 Gy)	Only study not to use concurrent chemotherapy
Tax 324	Carboplatin AUC 1.5, weekly	Radiation 2 Gy per day, 5 d a week for a total of 70-74 Gy
PARADIGM: responders	Carboplatin AUC 1.5, weekly	70 Gy over 7 wk	Regimen varied by response to induction
PARADIGM: non-responders	Docetaxel 20 mg/m2 weekly	Accelerated concomitant boost over 6 wk (72 Gy)	Regimen varied by response to induction
DeCIDE	CRT: five 14 d cycles of docetaxel (day 1), fluorouracil (day 0-4) and hydroxyurea (day 0-4)	Twice daily radiation (day 1-5)	Split course radiation