Relias Valerie, Maloney Antonia, Smith Melissa H, Saif Muhammad Wasif
Section of GI Cancers and Experimental Therapeutics, Tufts Cancer Center, Tufts University School of Medicine, 800 Washington Street, Boston, 02111, MA, USA.
Cancer Chemother Pharmacol. 2017 Aug;80(2):371-375. doi: 10.1007/s00280-017-3374-x. Epub 2017 Jun 29.
MPACT demonstrated a survival benefit of nab-paclitaxel plus gemcitabine versus gemcitabine in advanced pancreatic cancer (APC). However, sensory peripheral neuropathy is a dose-limiting toxicity and neuromodulators have shown limited, if any activity in ameliorating neuropathy. In colorectal cancer, the OPTIMOX ("stop-and-go") approach offered a strategy to reduce neuropathy. No data exist to support this strategy for nab-paclitaxel in APC.
Retrospective study of APC patients who developed grade 3 neuropathy during nab-paclitaxel plus gemcitabine was done. Nab-paclitaxel was held and then reinstituted upon radiological or tumor marker progression. Duration of disease control (DCC) was measured. We named this strategy "OPTINAB".
Seven patients out of 27 (25%) developed grade 3 neuropathy after an average of 4.2 months; nab-paclitaxel was suspended while gemcitabine was continued. Maintenance gemcitabine continued for a mean of 2.8 months. Upon progression (radiologic or CA19-9) nab-paclitaxel was re-instituted with gemcitabine. One patient could not tolerate nab-paclitaxel due to worsening of neuropathy while other six continued the combo with mean progression-free survival 2 (PFS2) of 2.2 months. The six patients continued nab-paclitaxel for a mean of PFS2 of 2.2 months (range 1-4 months). Nab-paclitaxel resulted in improvement of an average DDC with an average of (7.0 + 2.2 =) 8.2 months (range 8-13 months). Average overall survival for this group was 11.7 months (range 9.5-17 months). Reintroduction of nab-paclitaxel resulted in an average DDC of 9.4 months. Average overall survival (OS) for this group was 11.7 months.
"OPTINAB" approach improved PFS2 in these patients and was feasible as majority of the patient tolerated nab-paclitaxel. Although it is a small study, it supports the need for a randomized, prospective study to test the concept of "OPTINAB".
MPACT研究表明，在晚期胰腺癌（APC）中，纳米白蛋白结合型紫杉醇联合吉西他滨对比吉西他滨可带来生存获益。然而，感觉性周围神经病变是一种剂量限制性毒性，神经调节剂在改善神经病变方面的活性有限（即便有活性）。在结直肠癌中，OPTIMOX（“停停走走”）方案提供了一种减少神经病变的策略。目前尚无数据支持在APC中对纳米白蛋白结合型紫杉醇采用这一策略。
对在接受纳米白蛋白结合型紫杉醇联合吉西他滨治疗期间发生3级神经病变的APC患者进行回顾性研究。暂停纳米白蛋白结合型紫杉醇治疗，待出现影像学进展或肿瘤标志物进展时重新启用。测量疾病控制持续时间（DCC）。我们将这一策略命名为“OPTINAB”。
27例患者中有7例（25%）在平均4.2个月后发生3级神经病变；纳米白蛋白结合型紫杉醇暂停使用，吉西他滨继续使用。维持使用吉西他滨的平均时间为2.8个月。病情进展（影像学或CA19-9）时，纳米白蛋白结合型紫杉醇与吉西他滨重新联合使用。1例患者因神经病变恶化无法耐受纳米白蛋白结合型紫杉醇，其他6例继续联合治疗，无进展生存期2（PFS2）平均为2.2个月。这6例患者继续使用纳米白蛋白结合型紫杉醇的PFS2平均为2.2个月（范围1 - 4个月）。纳米白蛋白结合型紫杉醇使平均DCC改善，平均为（7.0 + 2.2 =）8.2个月（范围8 - 13个月）。该组患者的平均总生存期为11.7个月（范围9.5 - 17个月）。重新启用纳米白蛋白结合型紫杉醇后的平均DCC为9.4个月。该组患者的平均总生存期（OS）为11.7个月。
“OPTINAB”方案改善了这些患者的PFS2，且由于大多数患者耐受纳米白蛋白结合型紫杉醇，该方案可行。尽管这是一项小型研究，但它支持开展一项随机前瞻性研究以验证“OPTINAB”概念的必要性。
