Medical Oncology Department, Venice, Italy
M. G. Ghi , A. Paccagnella , I. Floriani , D. Garavaglia
Background: Concomitant platinum-based chemoradiation (CRT) is the standard treatment for locally advanced squamous cell carcinoma. As no consensus regarding the optimal concomitant platinum-based regimen exist, a literature based meta-analysis was performed. Methods: Randomized trials comparing radiation alone (RT) vs concomitant platinum-based CRT were identified by electronic search. The main endpoints were to compare the efficacy with regards to cisplatin total dose and platinum compounds (cisplatin vs carboplatin). Hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to measure the relative effect of treatments on overall survival (OS). Heterogeneity among trials was tested by Chi-Square test and I2 index. The incidence of Grade (G) 3-4 mucositis was also analyzed by means of a Chi-Square test. Results: Fifteen trials were identified and 2502 patients were available for the analysis. No difference in OS was observed between cisplatin high dose (300mg/sqm) (HR 0.59, 95% CI 0.46-0.74) and cisplatin dose <300mg/sqm plus 5-fluorouracil (5FU) (HR 0.59, 95% CI 0.45- 0.77) when compared to RT alone. The HR of death was 0.68 (95% CI 0.54-0.86) for cisplatin at intermediate dose (200-225mg/sqm) without 5FU, 1.04 (95% CI 0.85-1.27) for cisplatin dose <150mg/sqm without 5FU and 0.69 (95% CI 0.59-0.79) for carboplatin-based CRT. The Grade 3-4 mucositis incidence was 57% for concomitant cisplatin high dose, 46.1% for cisplatin dose <300mg/sqm plus 5FU (P=0.023), and 45.9% for carboplatin based CRT (P=0.096). Conclusions: Our meta-analysis seems to suggest that there is a dose/efficacy relation for concomitant cisplatin total dose. Concomitant cisplatin dose <300mg/sqm plus 5FU give the same survival benefit of concomitant cisplatin high dose, with a significant lower incidence of G3-4 mucositis. No advantage in OS was observed between CRT with cisplatin total dose <150mg/sqm monochemotherapy and RT alone. CRT with carboplatin and cisplatin, independently from doses and schedules, seems to give the same survival advantage over RT alone with a similar G3-4 mucositis incidence.
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