Ahlgren J D
Division of Hematology and Oncology, The George Washington University Medical Center, Washington, DC 20037, USA.
Cancer. 1996 Aug 1;78(3 Suppl):654-63. doi: 10.1002/(SICI)1097-0142(19960801)78:3<654::AID-CNCR46>3.0.CO;2-V.
Pancreatic cancer is an aggressive disease and its patients typically have a short survival, usually marked by pain and rapid debilitation. The disease has been considered relatively chemoresistant, although many chemotherapy regimens have been described.
Clinical results with chemotherapy, since the first publication of response in 1960, were reviewed for efficacy and toxicity. Emphasis was given to prospective trials with adequate power and clear evaluation criteria and endpoints.
Published response rates vary enormously in this disease, with rates in earlier single-institution trials tending to be much higher than those in studies with stringent response criteria, particularly recent cooperative group trials. Using stringent criteria, the upper limit of the objective response rate is approximately 20%. No convincing improvements in median survival can yet be attributed to chemotherapy. Few trials have measured quality of life, but symptomatic palliation rates may exceed objective response rates. Some low-toxicity regimens (such as those based on infusional 5-FU) yield response rates as high as some more toxic combinations.
Many early trials significantly overstate the efficacy of chemotherapy for patients with pancreatic cancer, apparently due to flexibility of response criteria. However, useful symptomatic palliation may occur even without an objective partial response. It is possible that slow resolution of the desmoplastic component of these tumors may underestimate tumor killing. Thus, quality of life is an important parallel endpoint (with survival and response) in chemotherapy trials in this disease.
胰腺癌是一种侵袭性疾病,患者通常生存期较短,常伴有疼痛和迅速衰弱。尽管已有许多化疗方案被描述,但该疾病一直被认为相对耐药。
回顾自1960年首次发表化疗反应以来的临床化疗结果,以评估疗效和毒性。重点关注具有足够样本量以及明确评估标准和终点的前瞻性试验。
该疾病已发表的缓解率差异极大,早期单中心试验的缓解率往往远高于那些具有严格缓解标准的研究,尤其是近期的协作组试验。采用严格标准时,客观缓解率的上限约为20%。化疗尚未使中位生存期有令人信服的改善。很少有试验对生活质量进行评估,但症状缓解率可能超过客观缓解率。一些低毒性方案(如基于持续输注5-氟尿嘧啶的方案)的缓解率与一些毒性更强的联合方案一样高。
许多早期试验明显高估了化疗对胰腺癌患者的疗效,这显然是由于缓解标准的灵活性所致。然而,即使没有客观的部分缓解,也可能出现有效的症状缓解。这些肿瘤的促结缔组织增生成分消退缓慢可能会低估肿瘤杀伤效果。因此,在该疾病的化疗试验中,生活质量是一个重要的平行终点(与生存期和缓解率并列)。