Retrospective Study of Cisplatin/Carboplatin, 5-Fluorouracil Plus Cetuximab (EXTREME) for Advanced-stage Salivary Gland Cancer

Abstract

Background/Aim: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5fluorouracil plus cetuximab (EXTREME). Patients and Methods: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. Results: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. Conclusion: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.Recurrent, locally advanced or distant metastatic salivary gland cancer (SGC) has no established systemic therapy. Surgical resection followed by radiation therapy is sometimes performed for SGC of advanced stage or with poor prognostic factors (1). SGC has different kinds of histopathological subtypes and three grading systems (2, 3), so it is frequently difficult to choose an optimum treatment.Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that has an important role in tumor growth and progression in various kinds of cancer and serves as a therapeutic target of molecular targeted therapy (e.g., cetuximab) (4, 5). In fact, the EXTREME regimen (cisplatin/carboplatin, 5-fluorouracil plus cetuximab) is 979 This article is freely accessible online.

Efficacy of Cetuximab Combined with Paclitaxel in Patients with Recurrent Salivary Gland Carcinoma: A Retrospective Observational Study

“…However, anti-EGFR therapies, besides our study, could not show efficacy in patients with SGC. Two studies using anti-EGFR monotherapy (cetuximab [21] and gefitinib [22]) showed no clinical responses, and one study using cetuximab combined with cisplatin and fluorouracil showed poor ORR (11.1%) [27]. Thus, it is surprising that our study demonstrated the promising efficacy of Cmab-PTX in patients with recurrent SGC, with an ORR of 71.4%, despite all cases being high-grade histological types.…”

“…All the previous studies regarding anti-HER-2 therapies subjected to HER-2 positive SGC patients [19,[23][24][25][26]28]. However, previous studies using anti-EGFR therapies with poor clinical outcomes included patients with negative EGFR [21,22,27]. In our study, all measurable patients with SGC were positive for EGFR in immunostaining and showed preferable results with anti-EGFR therapy.…”

“…PTX monotherapy showed moderate efficacy; ORR was 26% in patients with SGC [40]. Conversely, cisplatin with fluorouracil showed no response against patients with ACC [41], and only 10.5% of patients with SGC achieved a clinical response with EXTREME regimen [27]. Accordingly, taxane-based chemotherapy might be more feasible to combine with molecular-targeted therapy than platinum-based anticancer drug in SGC.…”

“…Because HER family proteins play a critical role in carcinoma proliferation [17], anti-HER family therapies are used in various types of carcinoma [18]. Previous reports regarding anti-HER family therapies for patients with SGC are summarized in Table 2 [19][20][21][22][23][24][25][26][27][28]. Studies with anti-HER-2 therapies showed that ORR was more than 50% in patients with SDC.…”

First Case Report of Bilateral Parotid Lymphoepithelial Carcinoma

“…Chemotherapy is not consensual (10,12,13,15). Nakano and colaborators (2022) retrospectively identified 19 patients through a study who were treated with the EXTREME chemotherapy regimen (cisplatin/carboplatin, 5-fluorouracil plus cetuximab) for advanced-stage salivary gland cancer, where the best responses observed in this study were only partial responses observed in 2 cases (mucoepidermoid carcinoma and one of LEC), but even with this fact all cases had treatment discontinuation due to adverse effects (16).…”