Ifosfamide-vinorelbine-cisplatin versus pemetrexed-cisplatin in advanced non-small cell lung cancer

OBJECTIVE: Lung cancer is one of the highest incidence and death rate of cancer in the world. Non‐small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. More than 2/3 patients with NSCLC often have advanced disease at the time of diagnosis. Although therapeutic methods for lung cancer developed rapidly in recent years, there was no standard third line therapy for advanced NSCLC. The objective of this retrospective study was designed to compare the efficacy and toxicities of Ifosfamide‐vinorelbine‐cisplatin (INP) versus pemetrexed‐cisplatin (AP) as third line therapy in advanced NSCLC. METHODS: This study was performed to enroll advanced NSCLC patients who failed from the first and second line therapy at Department of Medical Oncology of Jiangmen Central Hospital of Sun Yat‐Sen University. From April 1, 2013 to April 1, 2015, 158 cases met criteria and were randomly assigned to INP group(78 cases) and AP group(80 cases). Patients' characteristics including gender, age, performance status, stage, histology, smoking status and previous treatments were similar between groups. In INP group, the Ifosfamide was administrated at the dose of 1.2 g/m2 from day 1 to 2, Vinorelbine was 20 mg/m2 on day 1 and 8; while in AP group, Pemetrexed was 500 mg/m2 from day 1. In both groups the Cisplatin was administrated at the dose of 25 mg/m2 from day 1 to 3. Both regiments were repeated every 21 days, a total of 4 cycles. Each patient received at least 2 courses of chemotherapy until disease progressed or unacceptable toxicity occurred. After the end of the initial 2 courses and 4 courses, tumor response rate would be accessed according to RECIST criteria. The toxicity was accessed according to NCI‐CTC Version 3.0. The progression free survival (PFS) was defined from the first day of chemotherapy to progression of disease or death of any cause. RESULTS: All of 158 patients enrolled were evaluated. The median follow‐up was 13 months.The objective response rate was 12.8%(10/78) in INP group and 17.5%(14/80) in AP group, with no statistically significant difference (chi2=0.671, P=0.413), and the clinical benefit rate was 53.8%(42/78) and 57.5%(46/80) respectively, with no statistically significant difference (chi2=0.214, P=0.644). Median progression free survival (PFS) was 153 days in INP group and 189 days in AP group, with statistically significant difference (P=0.027). The adverse reactions can be tolerated. Leukopenia and neutropenia were more frequent in INP group (74.4% vs 37.5%, P=0.000 and 64.1% vs 37.5%, P=0.001), with statistically significant difference. Thrombocytopenia and anemia were similar in both groups (30.8% vs 40.0%, P=0.225 and 59.0% vs 52.5%, P=0.413).Nausea and vomiting were 79.5%(62/78) in INP group and 55.0%(44/80) in AP group, with statistically significant difference (P=0.001). There were more patients had Grade 1/2 peripheral neurotoxicity and phlebitis (64.1% vs 37.5%, P=0.001 and 25.6% vs 2.5%, P=0.000), with statistically significant difference. There was 12.8% of patients had G1/2 urinary irritation symptoms in INP group while no patients had in AP group. CONCLUSIONS: The efficacy of both regimens was similar in both groups. The media PFS was longer in AP group than that in INP group, with statistically significant difference. The haematological taxicities and non‐haematological toxicities were more common in INP group than those in AP group, with statistically significant difference. If patients have no economic problems, AP regimen is better than INP regimen as third line chemotherapy in advanced NSCLC, especially in adenocarcinoma.