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Head and Neck Cancer


Table 1: Summary of Completed and Ongoing Clinical Studies Incorporating Cetuximab into Treatment Regimens for LA SCCHN


Study/Phase and Description Number of Patients


Treatments Major Results Reference(s)


Clinical Studies using Concurrent Cetuximab with Radiotherapy or Chemoradiotherapy for Locally Advanced Squamous Cell Cancer of the Head and Neck


Cetuximab with Radiotherapy Phase III multinational, randomised study (3- and 5-year data).


Concurrent therapy CTX + RT (unresectable tumours)


424 patients Patients randomised 1:1 to 3-year data: median locoregional control: median overall survival for CTX+RT=49 Bonner et al.,


with LA SCCHN high-dose RT alone (213 patients) 24.4 months with CTX+RT and 14.9 months 200630 or high-dose RT plus weekly CTX with RT alone (p=0.005). 5-year data: (211 patients) – initial dose: 400mg/m2, then 250mg/m2 weekly for duration of RT


months and RT alone=29.3 months (p=0.018).


5-year overall survival for CTX+RT=45.6% and RT alone=36.4%. Grade ≥2 acneiform rash associated with improved survival. Some Grade 3/4 AEs increased in the CTX+ RT versus RT alone arm: skin reactions (35.1 versus 21.2%), acneiform rash (16.8 versus 1.4%), infusion reactions (2.9 and 0%) (p<0.05). Concomitant high-dose RT plus CTX improves locoregional control in LA SCCHN and reduces mortality without increasing toxic effects associated with RT to the head and neck


Cetuximab with Chemoradiotherapy Phase II open-label,


69 patients with CTX 400mg/m2, then


single-arm study ECOG 3303. (98% stage IV) Concurrent CTX+CRT (unresectable tumours)


LA SCCHN 250mg/m2/week, with RT


(70Gy/2Gy/day x 7 weeks) and CPT 75mg/m2. In the absence of disease progression or


toxicity, patients could continue CTX weekly for >6 months


Pilot phase II single arm. Concurrent CTX+CRT (unresectable tumours)


boost: 1.6Gy 4–6 hours


later weeks 5–6 [70Gy total]), +CPT (100mg/m2 intravenously weeks 1 and 4) and CTX (400mg/m2 intravenously


Preliminary results: weekly CTX, with concurrent CPT and full dose RT is feasible in fit patients with unresectable LA SCCHN. Toxicities included: acneiform rash and possible increase in Grade ≥3 mucositis. Longer follow-up needed for locoregional control and survival end-points


22 patients stage III Boost RT (1.8Gy/day in weeks 1–6; After median 52-study month follow-up, or IV, M0, LA SCCHN


week 1, followed by 250mg/m2 weeks 2–10)


Phase II single-arm study. Alternating radiotherapy and chemotherapy plus CTX (unresectable tumours)


stage III/IV LA SCCHN


24 patients with CPT 20mg/m2/day and bolus 5-FU 200mg/m2/day. RT,


(2Gy/day), in pauses between the CT cycles and after the last CT week, up to total of 70Gy CTX initial dose was 400mg/m2, then 250mg/m2 weekly


Phase III randomised RTOG 0522 study.


Concurrent CTX+CRT (unresectable tumours)


Phase III randomised, open label, parallel-arm study GORTEC 2007-01.


Concurrent CTX+CRT versus CTX+RT


(unresectable tumours) 945 patients* Comparator: CPT over 1 hour


with LA SCCHN (100mg/m2) during RT. (recruitment complete)


406 patients recruitment)


Experimental: addition of CTX (400mg/m2, then 250mg/m2 weekly) to comparator regimen Comparator: CTX 400mg/m2


with LA SCCHN initially then 250mg/m2/week (planned


over 8 weeks +RT (70Gy in 7 weeks). Experimental: CTX 400mg/m2 initially then


250mg/m2/week over 8 weeks +CBN 70mg/m2/day, 5-FU 600mg/m2/day+RT (70Gy in 7 weeks)


3-year overall survival rate: 76%, 3-year progression-free survival: 56% and 3-year locoregional control: 71%. Toxicities were typical of those expected with concurrent CPT+RT. Further safety investigation is needed but initial efficacy findings were encouraging


At 3 months: 11 complete responses,


Langer et al., 200833


and 201031


Pfister et al., 200634


Merlano et al.,


5 partial responses. Grade 3 or 4 toxicities: 200735 febrile neutropenia (20%), diarrhoea (20%), hypomagnesaemia (10%), mucositis (60%). Unexpected skin toxicity in 18/20 patients. Chemoradiation plus CTX led to a high CR rate and was feasible


Study ongoing. Aims to evaluate the addition of CTX to RT+CPT regimen on disease-free survival, overall survival, locoregional control and correlation of PET scan findings with outcome parameters


Ang et al., 200736


Study ongoing. Aims to evaluate the addition NCT0060928437 of concomitant CT (CBN/5-FU) to CTX+RT on progression-free survival and locoregional control over 3 years


18


EUROPEAN ONCOLOGY & HAEMATOLOGY


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