Reni M, Cereda S, Bonetto E, Viganò M G, Passoni P, Zerbi A, Balzano G, Nicoletti R, Staudacher C, Di Carlo V
Department of Oncology, San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy.
Cancer Chemother Pharmacol. 2007 Feb;59(3):361-7. doi: 10.1007/s00280-006-0277-7. Epub 2006 Jun 29.
PEFG regimen (cisplatin and epirubicin 40 mg/m2 day 1, gemcitabine 600 mg/m2 days 1 and 8, 5-fluorouracil (FU) 200 mg/m2/day continuous infusion) significantly improved the outcome of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine in a previous phase III trial. This regimen was subsequently modified in a dose-finding study by increasing dose intensity of cisplatin and epirubicin (both at 30 mg/m2 every 14 days) and of gemcitabine (at 800 mg/m2 every 14 days). Results of a consecutive series treated by dose-intense PEFG regimen are herewith reported.
Dose-intense PEFG was administered to chemotherapy-naive patients with stages III-IV PA, < 75 years, performance status (PS) > 50, till progressive disease or for a maximum of 6 months.
Between January 2004 and June 2005, 49 (31 or 63% metastatic) patients, median age 62 years, median PS 80, were treated with dose-intense PEFG. Partial response and stable disease was observed in 24 (49%) and 16 (33%) patients, respectively; 31 patients were progression-free at 6 months (PFS-6 = 63%). Median survival was 10.5 months and 1-year overall survival (OS) was 48% (95% confidence interval: 33-61%). Main grade 3-4 toxicity was: neutropenia in 26% of patients, stomatitis and fatigue in 8%, anaemia, diarrhoea, nausea/vomit in 6%, febrile neutropenia and thrombocytopaenia in 4%, hand-foot syndrome in 2%.
When compared with 84 patients treated by classical PEFG at the same institution, dose-intense PEFG was not inferior in terms of PFS-6 (63 versus 57%), 1-year OS (48 versus 42%) and response rate (49 versus 49%); it allowed to increase dose intensity for gemcitabine by 32%, for cisplatin and epirubicin by 36% (FU reduced by 3%), to significantly reduce grade 3-4 hematological toxicity (neutropenia: 26 versus 86%; P < 0.00001; thrombocytopaenia: 4 versus 58%; P < 0.00001) and to reduce by one-third the number of outpatient accesses. The new PEFG schedule appears more suitable for clinical use and should be preferred as a basis for further development of therapeutic strategies against pancreatic cancer.
在之前的一项III期试验中，PEFG方案（顺铂和表柔比星40mg/m²，第1天；吉西他滨600mg/m²，第1天和第8天；5-氟尿嘧啶（FU）200mg/m²/天持续输注）相较于标准吉西他滨方案显著改善了晚期胰腺腺癌（PA）患者的预后。随后在一项剂量探索研究中对该方案进行了修改，增加了顺铂和表柔比星（均为每14天30mg/m²）以及吉西他滨（每14天800mg/m²）的剂量强度。本文报告了采用剂量密集型PEFG方案治疗的连续系列患者的结果。
对年龄<75岁、体能状态（PS）>50的III-IV期PA初治患者给予剂量密集型PEFG方案，直至疾病进展或最长治疗6个月。
2004年1月至2005年6月期间，49例（31例或63%为转移性）患者接受了剂量密集型PEFG方案治疗，中位年龄62岁，中位PS为80。分别有24例（49%）和16例（33%）患者出现部分缓解和病情稳定；31例患者在6个月时无进展（无进展生存期6个月（PFS-6）=63%）。中位生存期为10.5个月，1年总生存率（OS）为48%（95%置信区间：33-61%）。主要的3-4级毒性反应为：26%的患者出现中性粒细胞减少，8%的患者出现口腔炎和疲劳，6%的患者出现贫血、腹泻、恶心/呕吐，4%的患者出现发热性中性粒细胞减少和血小板减少，2%的患者出现手足综合征。
与同一机构采用经典PEFG方案治疗的84例患者相比，剂量密集型PEFG方案在PFS-6（63%对57%）、1年OS（48%对42%）和缓解率（49%对49%）方面并不逊色；它使吉西他滨的剂量强度增加了32%，顺铂和表柔比星的剂量强度增加了36%（FU减少了3%），显著降低了3-4级血液学毒性（中性粒细胞减少：26%对86%；P<0.00001；血小板减少：4%对58%；P<0.00001），并使门诊就诊次数减少了三分之一。新的PEFG方案似乎更适合临床应用，应作为进一步开发胰腺癌治疗策略的基础而优先选用。
