A Comparison Of Efficacy Of Neoadjuvant Chemotherapy With Gemcitabine Versus Paclitaxel Plus Platinumin Locoregionally Advanced Nasopharyngeal Carcinoma

Objective: To compare the efficacy of volumetric reduction of the primary lesion and metastatic lymph nodes after neoadjuvant chemotherapy,survival rates and safety of neoadjuvant chemotherapy with gemcitabine plus platinum(nedaplatin or cisplatin)(GP regimen)versus paclitaxel plus platinum(nedaplatin or cisplatin)(TP regimen)in locoregionally advanced nasopharyngeal carcinoma.Methods: From January 2012 to December 2014,149 patients with III-IV stage,non-metastatic nasopharyngeal carcinoma receiving neoadjuvant chemotherapy with GP regimen or TP regimen were retrospectively analyzed.The gross tumor volume of the primary site and metastatic lymph nodes were delineated on magnetic resonance imaging before and after(21±7 days from the first day of the second cycle of neoadjuvant chemotherapy)neoadjuvant chemotherapy.According to the relationship between volumetric change criteria and Response Evaluation Criteria in Solid Tumors,65% decrease in tumor volume was defined as partial response(PR),73% increase in volume was defined as progressive disease(PD).The changes in tumor volume after neoadjuvant chemotherapy were calculated and compared between the two groups.Treatment toxicities were also reported.In order to explore the survival difference between patients receiving GP regimen and TP regimen,a total of 373 patients with locoregionally advanced nasopharyngeal carcinoma between January 2005 and December 2014 in our hospital who received neoadjuvant chemotherapy with GP regimen or TP regimen combined with concurrent chemoradiotherapy(CCRT)with platinum(nedaplatin or cisplatin)were retrospectively analyzed.104 patients treated with GP regimen combined with CCRT were matched with 104 patients who received TP regimen combined with CCRT using propensity score matching.Results: Among the 149 patients for tumor volumetric reduction analyse,76 received GP regimen,73 received TP regimen.After neoadjuvant chemotherapy,7,11 and 58 patients achieved CR,PR and SD,respectively,for primary site volume reduction analyse in the GP group.The overall response rate(CR+PR)for primary site was 23.68%.10,16,46 patients achieved CR,PR and SD,respectively,for metastatic lymph nodes analyse(4 patients were excluded because of being diagnosed as N0 category)in the GP group.The overall response rate(CR+PR)for metastatic lymph nodes was 36.11%.3,22,51 achieved CR,PR and SD,respectively,for the whole tumor volume change analyse in the GP group.The overall response rate(CR+PR)for the whole volume was 32.89%.In the TP group,3,5 and 65 patients achieved CR,PR and SD,respectively,for primary site volume reduction analyse.The overall response rate(CR+PR)for primary site was 10.96%.4,9,55 patients achieved CR,PR and SD,respectively,for metastatic lymph nodes analyse(5 patients were excluded because of being diagnosed as N0 category).The overall response rate(CR+PR)for metastatic lymph nodes was 19.12%.0,8,65 achieved CR,PR and SD,respectively,for the whole tumor volume change analyse.The overall response rate(CR+PR)for the whole volume was 10.96%.The overall response rates(CR+PR)of the GP group were significantly higher than those of the TP group in primary site,metastatic lymph nodes and the whole tumor volume(?2=4.186,p=0.041;?2=5.025,p=0.025;?2=10.391,p=0.001).Patients in the GP group experienced more leucopenia(76% vs.42%,p<0.001),neutropenia(72% vs.55%,p=0.026),anemia(51% vs.16%,p<0.001)and thrombocytopenia(28% vs.8%,p=0.002)than those in the TP group.There were no significant differences between the two groups in non-hematologic toxicities(all p-values >0.05).Among the 373 patients analyzed for survival difference,269 received GP regimen,104 received TP regimen.With a median follow-up time of 51 months(range,5–134 months),the 4-year overall survival(OS),progression-free survival(PFS)rates of the GP group were significantly higher than those of the TP group(OS,87.6% vs.83.3%,p=0.002;PFS,81.4% vs.68.0%,p=0.025)while the statistic differences of 4-year locoregional relapse-free survival(LRRFS)and distant metastasis-free survival(DMFS)rates were not observed between the two groups(LRRFS,90.7% vs.82.1%,p=0.105;DMFS,88.9% vs.80.6%,p=0.094).After being matched,the 4-year overall survival(OS),progression-free survival(PFS),locoregional relapse-free survival(LRRFS)and distant metastasis-free survival(DMFS)rates were 87.6%,74.8%,84.9% and 86.3%,respectively,in the GP group and 83.3%,68.0%,82.1% and 80.6%,respectively,in the TP group.No statistically significant survival differences were found between the two groups(all p-values >0.05).Conclusion: The GP regimen has stronger power in tumor volume reduction than TP regimen.However,this difference may not transform into survival benefits.The GP group has more hematologic toxicities than TP group.A phase III study to definitively test these results is warranted.