Background: Both gemcitabine- and 5-fluorouracil (5-FU)-based chemotherapy regimens have demonstrated efficacy in metastatic pancreatic cancer (MPC). Alternating these regimens may reduce toxicity, slow resistant cancer biology emergence, and provide a platform for the addition of other therapeutic agents. Alternating gemcitabine/nab-paclitaxel (GA) and 5-FU/leucovorin/irinotecan (FOLFIRI) in MPC has previously been reported at our own institution and elsewhere. An extension of our institutional observations is reported here. Methods: Patient eligibility required the following: biopsy-proven de novo MPC, no prior evidence of disease on CT, ECOG performance status (PS) ≤ 2, and bi-dimensionally measurable disease. Treatment (Tx) entailed gemcitabine 1000 mg/m2and nab-paclitaxel 125 mg/m21, (8), 15 alternating every 8 weeks (2 cycles) with FOLFIRI using standard dosing. Patients were radiographically re-staged every 8 weeks. Tx spanned up to 12 cycles. Tx thereafter was decided following patient/physician discussion. Results: Median overall survival (mOS) was 13.2 months (95% CI 10.9–16.5 months). Median progression-free survival (mPFS) was 8.5 months (95% CI, 7.1–9.9). The 6-, 12-, 18-, and 24-month OS rates were 88%, 54%, 36%, and 20%, respectively. The disease control rate at 16 weeks was 83% (37% PR, 46% SD). Hematologic toxicity grade ≥ 3 included 9.3% anemia, 10.2% neutropenia, and 4.6% thrombocytopenia. Neutrophil growth factors were not used in this cohort. Non-hematologic toxicities grade ≥ 3 included neuropathy 0.9%, nausea/vomiting 0.9%, and diarrhea 0.9%. No patients experienced mucositis on this regimen. Conclusions: Alternating GA/FOLFIRI in MPC has a favorable toxicity profile in comparison to current standard regimens. Median OS was at least competitive with standard regimens, and longer-term (18 and 24 months) OS seemed particularly encouraging. Treatment for ≥48 weeks and ECOG PS of zero at the time of treatment initiation were prognostically significant. Further investigation using this regimen including randomized comparisons, the incorporation of molecular data, and use of additional agents is merited.
背景：基于吉西他滨和5-氟尿嘧啶（5-FU）的化疗方案在转移性胰腺癌（MPC）治疗中均显示出疗效。交替使用这些方案可能降低毒性、延缓耐药性肿瘤生物学的出现，并为联合其他治疗药物提供平台。此前，我们机构及其他研究单位已报道过在MPC中交替使用吉西他滨/白蛋白结合型紫杉醇（GA）与5-氟尿嘧啶/亚叶酸/伊立替康（FOLFIRI）的方案。本文报告了我们机构观察结果的延伸分析。 方法：患者需满足以下条件：经活检证实为初诊MPC、CT检查无既往疾病证据、ECOG体能状态（PS）≤2分，且具有二维可测量病灶。治疗方案为：吉西他滨1000 mg/m²联合白蛋白结合型紫杉醇125 mg/m²（第1、8、15天给药），每8周（2个周期）与标准剂量的FOLFIRI方案交替使用。每8周进行影像学再分期评估。治疗最多持续12个周期，后续治疗方案经医患共同讨论决定。 结果：中位总生存期（mOS）为13.2个月（95% CI 10.9–16.5个月）。中位无进展生存期（mPFS）为8.5个月（95% CI 7.1–9.9）。6、12、18和24个月总生存率分别为88%、54%、36%和20%。16周时疾病控制率达83%（部分缓解37%，疾病稳定46%）。≥3级血液学毒性包括：贫血9.3%、中性粒细胞减少10.2%、血小板减少4.6%。本队列未使用粒细胞生长因子。≥3级非血液学毒性包括：神经病变0.9%、恶心/呕吐0.9%、腹泻0.9%。该方案未出现黏膜炎病例。 结论：与现行标准方案相比，GA/FOLFIRI交替方案在MPC治疗中具有更优的毒性特征。其中位总生存期至少与标准方案相当，而长期（18和24个月）生存率尤其令人鼓舞。治疗持续时间≥48周及治疗起始时ECOG PS为零分具有显著预后意义。该方案值得进一步研究，包括开展随机对照试验、整合分子生物学数据以及联合其他治疗药物。
肿瘤(癌症)患者之家