Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer

Abstract

To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). This was a phase I dose escalation study of matuzumab at 400 and 800 mg weekly and 1200 mg every 3 weeks combined with ECX (epirubicin 50 mg m À2 , cisplatin 60 mg m À2 on day 1 and capecitabine 1000 mg m À2 daily). Patients were treated until disease progression, unacceptable toxicity or for a maximum of eight cycles. Twenty-one patients were treated with matuzumab at three different dose levels (DLs) combined with ECX. The main dose-limiting toxicity (DLT) was grade 3 lethargy at 1200 mg matuzumab every 3 weeks and thus 800 mg matuzumab weekly was the maximum-tolerated dose (MTD). Other common toxicities included rash, nausea, stomatitis and diarrhoea. Pharmacokinetic evaluation demonstrated that the coadministration of ECX did not alter the exposure of matuzumab. Pharmacodynamic studies on skin biopsies demonstrated inhibition of the EGFR pathway. Objective response rates of 65% (95% confidence interval (CI): 43 -82), disease stabilisation of 25% (95% CI: 11 -47) and a disease control rate (CR þ PR þ SD) of 90% were achieved overall. The MTD of matuzumab in combination with ECX was 800 mg weekly, and at this DL it was well-tolerated and showed encouraging antitumour activity. At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT-3.

The Impact of Obesity on Outcomes Following Resection for Gastric Cancer

“…The institutional tumor board decided whether perioperative chemotherapy had to be given. Patients with lymph node metastases and/or ≥ T3 tumor were recommended perioperative chemotherapy with standardized regimens (5-FU, epirubicin and cisplatin [9,10] or docetaxel, cisplatin, and capecitabin [11] ). For tumor staging, the 7th edition of the American Joint Committee on Cancer/Union for International Cancer Control (UICC) staging system was applied [12] .…”

Peptide mimotopes recognized by antibodies cetuximab and matuzumab induce a functionally equivalent anti-EGFR immune response

“…In clinical studies prolonged treatment with cetuximab or matuzumab has generally been well tolerated, with skin reactions such as an acne-like rash being the most common side effect (Baselga et al, 2005;Rao et al, 2008;Seiden et al, 2007). Furthermore, endogenous humoral and cellular anti-EGFR immune responses have been observed in cancer patients (Shomura et al, 2004), suggesting that limited autoimmunity to EGFR is acceptable.…”

EGFR Inhibitors as Therapeutic Agents in Head and Neck Cancer

“…At 800 mg/week, matuzumab in combination with epirubicin, cisplatin, and capecitabine (ECX) was well tolerated. Furthermore, in skin biopsies, decreased phosphorylation of EGFR and MAPK was detected [158]. Surprisingly, the phase II study of matuzumab in combination with ECX did not increase response or survival in patients with metastatic oesophagogastric cancer [159].…”