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Cetuximab in the Treatment of Locally Advanced Head and Neck Cancer Table 1 (cont.):


Study/Phase and Description Number of Patients


Cetuximab in Post-induction Therapy Only Phase II randomised TREMPLIN 153 patients


(resectable tumours) larynx/


hypopharynx cancer started


Treatments Major Results Reference(s) Clinical Studies using Cetuximab as Induction and/or Post-induction Therapy for Locally Advanced Squamous Cell Cancer of the Head and Neck 3 cycles of DTX+CPT both


study CTX used post-induction with stage III-IV 75mg/m2 on day 1 and 5-FU 750mg/m2/day on days 1–5. If response ≥50%, patients


received either A: RT (70Gy)+CPT 115 patients randomised, no significant Lefebvre et al.,


difference in larynx preservation after 3 months 200938 (93% arm A, 96% arm B). CTX better tolerated than CPT. Arm A: 50% had CPT-related toxicity; Arm B: 26% had CTX-related toxicity. Induction


induction (100mg/m2 on days 1, 22 and 43) chemotherapy followed by RT with concurrent chemotherapy or B: CTX (400mg/m2 initial dose before RT and 250mg/m2 after) +RT (7 weeks)


CTX was better tolerated than with concurrent CPT with the same larynx preservation rate 3 months after treatment


Cetuximab in Induction Therapy or in Induction and Post-induction Therapy Phase II single-arm trial CTX used during induction (unresectable tumours)


68 patients LA SCCHN 2 cycles of DTX 75 mg/m2 and


with stage III/IV CPT 75mg/m2 day 1 and 5-FU 1,000mg/m2 96 hours every 3 weeks then RT (68Gy/4.5 weeks) with CTX one week before (400mg/m2) and weekly during RT (250mg/m2)


Phase II single-arm trial CTX used both during


50 patients with stage IV


induction and post-induction SCCHN (unresectable tumours)


DTX 75mg/m2 day 1, CPT


75mg/m2 day 1, 5-FU 750mg/m2, days 1 to 5, and CTX 250mg/m2 days 1, 8 and 15 (initial dose 400mg/m2 on cycle 1, day 1),


repeated every 21 days x 4 cycles. Then patients had accelerated RT with boost (69.9Gy) and CTX 250mg/m2 weekly


Phase II single arm study ECOG E2303


CTX used both during and post-induction


(resectable tumours)


74 patients with Induction chemotherapy: initially weekly CTX 250mg/m2, PCL 90mg/m2 and CBN (area under


stage III/IV SCCHN


(67 evaluable)


Responses at primary site: 65% after induction alone, and 100% after CRT – suggests high pathological complete


the curve [AUC]=2). Patients with response rate to induction CT+CTX positive biopsy at primary site at week 8 had restaging biopsy at


then CRT+CTX. Progression and survival data not yet available


week 14 after CTR (CTX 250mg/m2, PCL 30mg/m2, CBN [AUC=1] and 50Gy). If primary site was negative, patients had completion RT (68–72Gy) plus continued CTX+PCL+CBN


*An amendment to the study protocol dated 25 August 200863 increased the planned sample size to 945 patients from 720 patients.


AE = adverse event; AUC = area under the curve; CBN = carboplatin; CPT = cisplatin; CT = chemotherapy; CTR = chemoradiotherapy; CTX = cetuximab; DTX = docetaxel; ECOG = Eastern Cooperative Oncology Group; 5-FU = 5-fluorouracil; GORTEC = Groupe Oncologie Radiothérapie Tête et Cou (French Head and Neck Oncology and Radiotherapy Group); Gy = Gray units; LA SCCHN = locally advanced squamous cell cancer of the head and neck; PCL = paclitaxel; PET = positron emission tomography; RT = radiotherapy; RTOG = Radiation Therapy Oncology Group; TREMPLIN = The Radiotherapy With Cisplatin Versus Radiotherapy With Cetuximab After Induction Chemotherapy for Larynx Preservation study.


compared with 36.4% for radiotherapy alone.31 After a median follow-up


period of 60 months, the median survival time was 49 months for the combined therapy and 29.3 months for radiotherapy alone (HR for death 0.73, 95% CI 0.56–0.95; p=0.018). Indirect comparisons of the data from the Bonner trial with those of a meta-analysis (including 87 trials, mostly using concomitant chemotherapy, with a patient population of 16,665 and 5.5 years of follow-up) indicate that the survival advantage gained by adding cetuximab to radiotherapy is similar to that produced by adding chemotherapy to radiotherapy.32


The pattern of adverse events after five years in the Bonner study was similar to the earlier findings.31


The most commonly reported grade


3–4 adverse events in the radiotherapy alone and radiotherapy plus cetuximab groups were skin reaction (21.2 and 35.1%, respectively),


EUROPEAN ONCOLOGY & HAEMATOLOGY


mucositis/stomatitis (51.9 and 55.8%, respectively), dysphagia (29.7 and 26%, respectively), xerostomia (2.8 and 4.8%, respectively), acneiform rash (1.4 and 16.8%, respectively) and infusion reaction (0 and 2.9%, respectively).


Cetuximab with Chemoradiotherapy


An ongoing single-arm phase II study in Philadelphia, US, using cetuximab concurrently with chemoradiotherapy, is investigating the use of cetuximab added to a standard chemoradiotherapy regimen.33 The study recruited 69 patients with LA SCCHN (mostly stage IV disease) who received initial cetuximab (400mg/m2) followed by weekly doses (250mg/m2) in combination with radiotherapy (70Gy) and cisplatin (75mg/m2). Preliminary results demonstrated that 23% of patients experienced a complete response, 25% had a partial


19


Wanebo et al., 200741


Preliminary results: Results after DTX/CPT/ Mercke et al.,


5-FU: complete response: 1 patient, partial 200939 response: 15 patients. After RT with CTX: complete response: 10 patients, partial response: 18 patients. DTX/CPT/5-FU followed by RT with CTX is feasible with manageable toxicities


Adding CTX to DTX/CPT/5-FU CT produced a Mesia et al., high response rate, mainly complete response, 200940 potentially prolonging survival. Serious grade 3/4 AEs included: neutropenia 24%; neutropenic fever 20%; diarrhoea 12%


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