Chemotherapy in advanced lymphoepithelioma-like carcinoma (LELC) of lung

Abstract

Lymphoepithelioma-like carcinoma (LELC) of the lung, an Epstein-Barr virus (EBV)-associated undifferentiated carcinoma, is a rare entity of pulmonary malignancy. It appears to show predilection for young non-smoking Asians and is often resectable. However, little is known on the treatment of the even rarer locally advanced or metastatic cases. We have conducted a prospective study on the use of combination chemotherapy (5-fiuorouracil, leucovorin, and cisplatin) and radiotherapy in the treatment of locally advanced or metastatic LELC of lung. The inclusion criteria included age between 18 and 70 years, good performance state (WHO 0 or 1), histologically proven stage III or IV unresectable tumours, chemotherapy or radiotherapy naive, and nasopharyngeal carcinoma ruled out by endoscopic biopsy and magnetic resonance imaging, Exclusion criteria included previous malignancies, major organ failure and active uncontrolled infections. In-situ hybridization (ISH) for EBV-encoded small nuclear RNA (EBER) was performed on the biopsy specimens. Serological tests for EBV viral capsid antigen were serially performed during chemotherapy. Chemotherapy constituted four 4-weekly cycles of 5-fluorouracil (5-FU, 1000 mg/m2/day on day 1 to 4), leucovorin (200 mglm2 on day 1 to 4), and cisplatin (100 mg/m2 on day 1). Sequential local radiotherapy to mediastinum, given as 16 x 2.5 Gy/fraction, was included for locally advanced disease. Three cases (two females, mean age 42 years) of lung LELC were recruited between July 98 to June 99. Serum IgA titres to EBV were raised to the upper limit of detection of our laboratory at >1/640 in all three cases. These remained at the same level throughout the course of chemotherapy. Two of the patients had adequate biopsy specimens for detection of EBER which were positive. The tumour response rate to chemotherapy was 67% (~) partial response and 33% (~) stable disease. The latter was given local radiotherapy with partial response. Severe toxicities (NCI grade 3 or 4) included grade 3 vomiting (1 case) and grade 3 stomatitis (1 case). Our experience with the chemoradiotherapy helps in better understanding of the combined modality treatment in advanced or metastatic LELC of lung. This warrants future research in the treatment of this rather chemoradiosensitive malignancy.