Multicentre phase II study of cisplatin–etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study

Abstract

17. Herder GJ, van Tinterent TH, Golding RP et al. Clinical prediction Background: The optimal treatment of large-cell neuroendocrine carcinoma (LCNEC) of the lung remains unclear.Here, our primary objective was to assess the efficacy of cisplatin-etoposide doublet chemotherapy in advanced LCNEC. Accuracy of the pathological diagnosis and treatment toxicity were assessed as secondary objectives.Patients and methods: Prospective, multicentre, single-arm, phase II study with a centralised review of treatmentresponse and pathological data. Patients had untreated performance status (PS) 0/1 stage IV/IIIB LCNEC and received cisplatin (80 mg/m22 d1) and etoposide (100 mg/m22 d1-3) every 21 days. Results: Eighteen centres included 42 patients (mean age, 59 ± 9 years; 69% men; median of four cycles/patient). At least one grade-3/4 toxicity occurred in 59% of patients (neutropaenia, thrombocytopaenia, and anaemia in 32%, 17%, and 12%, respectively). The median progression-free survival (PFS) and overall survival (OS) were 5.2 months (95% confidence interval, CI, 3.1-6.6) and 7.7 months (95% CI, 6.0-9.6), respectively. The centralised pathologist review reclassified 11 of 40 (27.5%) patients: 9 as small-cell lung cancer, 1 as undifferentiated non-small-cell lung cancer, and 1 as atypical carcinoid. Survival data were not significantly changed by excluding the reclassified patients. Conclusions:The pathological diagnosis of LCNEC is difficult. The outcomes of advanced LCNEC treated with cisplatin-etoposide doublets are poor, similar to those of patients with advanced small-cell lung carcinoma (SCLC). Key words: carcinoma, clinical trial phase II, large cell neuroendocrine tumours, small-cell lung cancer introduction Large-cell neuroendocrine carcinoma (LCNEC) of the lung accounts for no more than 1% of all lung cancers. The typical histological features, first described in 1991 [1, 2], include large cells with abundant cytoplasm, a high mitotic rate, extensive necrosis, and a neuroendocrine growth pattern. The World Health Organisation currently classifies LCNEC as a distinct subtype of pulmonary large-cell carcinoma [3] and, therefore, as a subtype of non-small-cell lung carcinoma (NSCLC). However, LCNEC lacks the specific histologic features of NSCLC such as glandular or squamous differentiation, but instead displays evidence of neuroendocrine differentiation reminiscent of small-cell lung carcinoma (SCLC), although the malignant cells in SCLC are smaller, with scant cytoplasm, and invade the tissues in sheets. LCNECLCNEC shares genetic alterations with SCLC [4]. The higher mitotic rates and more extensive necrosis seen in LCNEC and SCLC are in contrast to the lower-grade neuroendocrine tumours, i.e. typical and atypical carcinoids. LCNEC and SCLC also share clinical characteristics including a preponderance of males and smokers and an aggressive clinical course [5][6][7][8][9]. The clinical outcome of LCNEC patients is poor, with overall 5-year survival rates ranging from 15% to 57%. Studies have demonstrated signifi...

Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung

“…As LCNEC shares many similarities with SCLC in terms of histologic structure, immunohistochemical staining characteristics, and molecular biology (5-7), SCLC-based chemotherapy was expected to show similar effectiveness in patients with LCNEC (8). In a multicenter prospective phase II study, however, combination chemotherapy with irinotecan and cisplatin resulted in inferior overall survival (OS) among patients with LCNEC than those with SCLC (9), suggesting a metabolic distinction between LCNEC and SCLC.…”

A Rare Presentation of Large Cell Neuroendocrine Carcinoma of the Lung

“…Currently treatment is guided by staging, with early stages (I-II) are typically surgically resected with mediastinal lymph node sampling or dissection. Later stages (III-IV) treated similarly to small cell carcinoma of the lung with etoposide and cisplatin [4]. However, even with these treatment regimens, prognosis remains poor.…”

Primary Large-Cell Neuroendocrine Carcinoma of the Breast Occurring in a Pre-Menopausal Woman

“…It is performed according to other types of invasive carcinoma, including anthracyclin and taxane, but it is unclear if these are appropriate for NEC. Phase II studies for LCNEC in the lung have been performed using existing lung cancer treatment drugs such as cisplatin, etoposide, lirinotecan [18,19]. In the pancreas or lung, genetic studies on NEC have advanced greatly, and some molecular-target agents are expected to become a future therapeutic approach [20].…”