Entry Detail
| General information | |
| Database: | DB00384 |
| Objective: | This study (EGF100262) sought to establish the recommendedphase II dose of lapatinib with chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). |
| Authors: | Harrington KJ, et al |
| Title: | Phase I study of lapatinib in combination with chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck. |
| Journal: | J Clin Oncol. |
| Year: | 2009 |
| PMID: | 19171712 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | lapatinib + chemoradiation |
| Study Type: | openlabel, doseescalation study |
| Key Patients Feature: | Patients with histologically confirmed stage III, IVA, or IVB SCCHNwho were suitable for definitive chemoradiotherapy were eligible. Patientswithhighriskfeatureseligibleforpostoperativechemoradiotherapywerealsopermitted, as were patients who had received prior adjuvant or neoadjuvantchemotherapy. patients were required to be at least 18 years old, with anEastern Cooperative Oncology Group performance status of 0 or 1 and adequate renal, hepatic, and bone marrow function. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | 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. |
| Primary End Point: | the recommended phase II dose |
| Secondary End Point: | safety and tolerability and clinical activity. |
| Patients Number: | 31 |
| Trial Results | |
| DLT_MTD: | Doselimiting toxicities (DLTs) included perforated ulcer in one patient in the 500mgcohort and transient elevation of liver enzymes in one patient in the 1, 000mg cohort. No DLTswere observed in the 1, 500mg cohort.the recommendedphase II dose was definedas lapatinib 1, 500 mg/d with chemoradiotherapy The most common grade 3 to 4 adverse eventswere radiation mucositis, radiation dermatitis, lymphopenia, and neutropenia |
| Objective Response Rate: | The objective response rate (ORR) was 81% (16 CRs and ninePRs); in the 17 patients receiving the recommendedphase II dose, theORRwas 65% (five CRs and six PRs; Table 5). All patients in 500 and1, 000mg cohorts achieved either CR or PR. In the 1, 500mg group, the ORR was 64%, two patients (12%) had progressive disease, andfour patients (24%) were considered nonassessable as a result of consentwithdrawal (n1), death (n2), andprotocol violation (n1). |
| Disease Control Rate: | 500 mg:100%; 1, 000 mg:100%; 1, 500 mg :64%;All Patients:80.6% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common grade 3 to 4 adverse events were radiation mucositis, radiation dermatitis, lymphopenia, and neutropenia. No patients experienced drugrelated symptomatic cardiotoxicity, and no interstitial pneumonitis was reported. |
| Conclusions: | The recommendedphase II dose is lapatinib 1,500 mgd with chemoradiotherapy in patients with LA SCCHN; this regimen is associated with an acceptable tolerability profile. Given these findings, randomizedphase II and III studies of lapatinib plus chemoradiotherapy have been initiated. |