Induction Chemotherapy with Paclitaxel Liposome, Nedaplatin, and Fluorouracil in Patients with Locally Advanced Nasopharyngeal Carcinoma: A Phase II Study

Abstract

A previous study found that adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy could improve failure-free survival in patients with locoregionally advanced nasopharyngeal carcinoma (NCT01245959). Paclitaxel liposome may have fewer side effects and work better than paclitaxel. Nedaplatin, a cisplatin analog, has been developed to decrease the toxicities induced by cisplatin, such as nephrotoxicity and gastrointestinal toxicity. In this study, we aimed to evaluate the safety and efficacy of induction chemotherapy with paclitaxel liposome, nedaplatin, and fluorouracil in patients with locally advanced nasopharyngeal carcinoma. In total we included 46 patients with newly diagnosed and pathologically confirmed stage III-IV nonkeratinized nasopharyngeal carcinoma in Nanjing University affiliated Drum Tower Hospital from 2015 May to 2017 June. Patients were treated with paclitaxel Liposome (135mg/m2), nedaplatin (60mg/m2), and fluorouracil (600mg/m2/day×5days), every 3 weeks for 2 cycles. If patients achieved partial response (PR) or complete response (CR) according to the RECIST criteria 1.0, another cycle was then added. Radiotherapy plus concurrent chemotherapy with nedaplatin was subsequently given with a total dose of 70Gy-74Gy with 2Gy per fraction in 35-37 fractions. Treatment response was evaluated 1 month after the end of the treatment. If patients achieved PR or CR, the treatment was consequently ended. The median age of studied patients was 50 years old (range, 25-74 years). Twenty-eight patients (60.9%, 28/46) had stage III disease, nine (19.6%, 9/46) had stage IVa disease and nine patients (19.6%, 9/46) were with stage IVb disease. Thirty-eight patients completed 3 cycles induction chemotherapy (80.1%, 38/47). CTCAE version 4.0 was referred to grade treatment-related toxicities. Three patients (6.5%, 3/46) developed grade 3 bone marrow suppression. Grade 1 nausea occurred in 3 patients (6.5%, 3/46) and grade 1 malaise occurred in 5 patients (10.9%, 5/46). After the induction chemotherapy, no patients achieved CR, 37 patients (80.4%, 37/46) achieved PR, 8 patients (17.4%, 8/46) were with stable disease (SD) and 2 patients (4.3%, 2/46) developed progressive disease (PD) (PR in primary tumor but with lung metastases). After induction chemotherapy plus concurrent chemoradiotherapy, all the patients achieved PR or CR. The median follow-up was 16 months (range, 8-33 months). Distant metastases occurred in 9 patients (5 patients with lung metastasis, 2 with bone metastasis, 2 with liver metastasis), and only 1 patient had in-field recurrence. Induction chemotherapy with paclitaxel liposome, nedaplatin, and fluorouracil is safe and efficient for patients locally advanced nasopharyngeal carcinoma. This regimen is well tolerated and might be especially helpful for patients with poor performance status. The long-term survival will be updated in future.