Phase I study of lapatinib in combination with chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck.
OBJECTIVE
This study (EGF100262) sought to establish the recommended phase II dose of lapatinib with chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).


METHODS
Patients were enrolled onto cohorts of escalating lapatinib dose (500, 1,000, and 1,500 mg/d). Patients received 1 week of lapatinib alone followed by 6.5 to 7 weeks of the same dose of lapatinib plus radiotherapy 66 to 70 Gy and cisplatin 100 mg/m(2) on days 1, 22, and 43 of radiotherapy. End points included safety/tolerability and clinical activity.


RESULTS
Thirty-one patients were enrolled (seven patients in each of the 500- and 1,000-mg cohorts and three in the 1,500-mg cohort; an additional 14 patients were enrolled at 1,500 mg in a safety cohort). Dose-limiting toxicities (DLTs) included perforated ulcer in one patient in the 500-mg cohort and transient elevation of liver enzymes in one patient in the 1,000-mg cohort. No DLTs were observed in the 1,500-mg cohort. Therefore, the recommended phase II dose was defined as lapatinib 1,500 mg/d with chemoradiotherapy. The most common grade 3 to 4 adverse events were radiation mucositis, radiation dermatitis, lymphopenia, and neutropenia. No patients experienced drug-related symptomatic cardiotoxicity, and no interstitial pneumonitis was reported. The overall response rate was 81% (65% at the recommended phase II dose).


CONCLUSIONS
The recommended phase II dose is lapatinib 1,500 mg/d with chemoradiotherapy in patients with LA SCCHN; this regimen is associated with an acceptable tolerability profile. Given these findings, randomized phase II and III studies of lapatinib plus chemoradiotherapy have been initiated.
Harrington
Kevin J
KJ
Head and Neck Unit, The Royal Marsden National Health Service Foundation Trust, 203 Fulham Rd, London SW3 6JJ, United Kingdom. Kevin.Harrington@icr.ac.uk
El-Hariry
Iman A
IA
Holford
Clare S
CS
Lusinchi
Antoine
A
Nutting
Christopher M
CM
Rosine
Dominique
D
Tanay
Mary
M
Deutsch
Eric
E
Matthews
Jennifer
J
D'Ambrosio
Consuelo
C
Turner
Simon J
SJ
Pandeshwara
Jagannatha S
JS
Bourhis
Jean
J
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D003131:Combined Modality Therapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D000077341:Lapatinib; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077341:Lapatinib