53%) of the combination group and in four patients (23.53%) of the chemotherapy group. No significant difference was found between the two groups (23.53% PLX4032 concentration vs 23.53%; P > 0.05). No serious adverse events were observed ( Table 3). The results of our study suggest that CT-PFNECII combined with second-line chemotherapy produced a higher response rate and improved survival than second-line chemotherapy in platinum-pretreated stage IV NSCLC. In addition, side effects of this combination
therapy were generally well tolerated. Compared with ORR of 11.76% and DCR of 35.29% in the chemotherapy group, the combination therapy provided an ORR of 23.53% and a DCR of 58.82% in platinum-pretreated stage IV NSCLC. Of note, one complete tumor regression was achieved in a patient by two cycles of combination treatment. More importantly, all patients who had lung tumor–related chest pain or dyspnea before our treatment achieved significant symptom relief even within 72 hours after CT-PFNECII treatment. Our pilot
study suggests that CT-PFNECII combined with second-line selleck chemicals llc chemotherapy has potent antitumor activity against platinum-pretreated NSCLC tumors. The benefit of our combination treatment in terms of survival outcomes was also quite encouraging. Considering that 29.41% of patients in our study population were platinum resistant (five patients in each arm) and 58.82% of the patients (10 of 17) received CT-PFNECII two times, the PFS of 5.4 months and OS of 9.5 months by our combination treatment were more valuable. The side effects of CT-PFNECII such as transient mild pain and cough in patients with lung cancer were minimal and well tolerated because only quite small amount of cisplatin and quite low concentration of ethanol were injected intratumorally. In addition, mild pneumothorax for and mild hemoptysis relating to the procedure were uncommon because we used a 22-gauge fine needle under the precise guidance of CT. Furthermore, combination of CT-PFNECII with second-line chemotherapy did not worsen common side effects of chemotherapy. No significant differences in chemotherapy-related adverse events in the two groups
were noted, indicating clinical safety of CT-PFNECII. We previously found that 5% ethanol could potently inhibit ABCG2 pump, which is a major drug transporter in protecting platinum-resistant NSCLC cells from cytotoxic agents. We also found that 5% ethanol-cisplatin injected intratumorally could eradicate cisplatin-resistant lung tumors by killing chemoresistant lung CSCs and normal lung cancer cells [10]. We speculate that the residual unkilled but damaged tumor cells in the 5% ethanol-cisplatin treatment group might be more fragile and sensitive to second-line chemotherapy agents. As a result, we speculate that CT-PFNECII treatment might have synergistic effects with systemic second-line chemotherapies, such as docetaxel or pemetrexed, in controlling platinum-pretreated NSCLC.