Improving Therapeutic Ratio in Head and Neck Cancer with Adjuvant and Cisplatin-Based Treatments

Table 1

Cisplatin-based chemoradiotherapy regimens employing IMRT techniques.

Clinical study	Patient no.	Radiotherapy	Chemotherapy	Clinical outcome
Phase II trial (Fury et al. 2012) [26] Bevacizumab with cisplatin plus intensity-modulated radiation therapy	42	IMRT total dose of 70 Gy	Cisplatin (50 mg/m^2 on days 1, 2, 22, 23, 43, and 44) and bevacizumab (15 mg/kg on days 1, 22, and 43)	TCP progression-free survival rate at 2 years: 75.9%; overall survival rate at 2 years: 88% NTCP, no increased toxicity with the addition of bevacizumab.
Phase III trial (SAKK 10/94) (Ghadjar et al. 2012) [24] Concomitant cisplatin and hyperfractionated radiotherapy versus hyperfractionated radiotherapy alone	224	Median total dose of 74.4 Gy, 1.2 Gy twice daily 5 days per week	Two cycles of cisplatin (20 mg/m^2 for 5 consecutive days during weeks 1 and 5)	TCP locoregional failure-free survival at 10 years: 40% versus 32%; metastasis-free survival: 56% versus 41%; cancer-specific survival at 10 years: 55% versus 43% in the combined arm versus radiotherapy alone NTCP, no difference in late toxicity.
Phase II study (Ma et al. 2012) [27] Concurrent cetuximab-cisplatin and intensity-modulated radiotherapy	30	IMRT median dose of 70 Gy	Cetuximab: initial dose of 400 mg/m^2 7–10 days before concurrent IMRT weekly cisplatin (30 mg/m^2/week) and cetuximab (250 mg/m^2/week)	TCP 2-year progression-free survival 86.5% NTCP grade 3-4 oropharyngeal mucositis: (87% and 33%) required short-term nasogastric feeding. Grade 3 radiotherapy-related dermatitis (20%) and 10% grade 3 cetuximab-related acneiform rash.
Phase II trial (Maguire et al. 2011) [35] Hyperfractionated intensity-modulated radiation therapy and concurrent weekly cisplatin	39	IMRT to high-risk planning target volume 70 Gy of 1.25 Gy twice daily fractions. Intermediate and low-risk PTVs of 60 Gy and 50 Gy, at 1.07 and 0.89 Gy/fraction	Cisplatin 33 mg/m^2 weekly	TCP actuarial 3-year overall survival: 80%, progression-free survival: 82%, and locoregional control:87% NTCP grade 3 + toxicities mucositis (38%), fatigue (28%), dysphagia (28%), and leukopenia (26%).
Clinical study (Montejo et al. 2011) [28] Accelerated radiotherapy with concurrent chemotherapy	43	IMRT with simultaneous integrated boost (67.5, 60, and 54 Gy in 30 daily fractions of 2.25, 2, and 1.8 Gy)	Cisplatin 40 mg/m^2 weekly or 100 mg/m^2 every 3 weeks during radiotherapy + weekly cetuximab (3 patients only)	TCP complete response: 74.4%; estimated 5-year locoregional control: 82%; NTCP tolerable acute and late toxicities.
Phase II trial (Lu et al. 2010) [25] Weekly cisplatin with concurrent intensity-modulated radiation therapy	22	IMRT of 69-70 Gy at 2.12–2.3 per fraction delivered to the PTV (including nodes)	Cisplatin 40 mg/m^2 weekly for six cycles	TCP 1-year overall survival: 95.5%, local recurrence-free survival: 95.5%, regional recurrence-free survival: 100%, and distant metastasis-free survival: 100% NTCP mild to moderate. Grade 3 stomatitis (27%), all other toxicities (less than 10%).
Clinical study (Lee et al. 2007) [36] Concurrent chemotherapy and intensity-modulated radiotherapy	31	Median dose of 70 Gy at 2.12 Gy/fraction to the PTVGTV; 59.4 Gy at 1.8 Gy/fraction to the PTV of high-risk subclinical disease	Cisplatin 2 to 3 cycles 100 mg/m^2 intravenously within 2 days every 3 weeks	TCP The 2-year local progression-free survival: 86%; regional progression-free survival: 94%; overall survival 63% NTCP grade 2 + mucositis occurred in 48% of patients; all had Grade 2 + pharyngitis during treatment.