一项奥沙利铂、伊立替康和 S-1 联合治疗（OX-IRIS）作为不可切除胰腺癌化疗的 I 期临床试验（HGCSG 1403）。
A Phase I Trial of Oxaliplatin, Irinotecan, and S-1 Combination Therapy (OX-IRIS) as Chemotherapy for Unresectable Pancreatic Cancer (HGCSG 1403).
机构信息
Division of Cancer Center, Hokkaido University Hospital, Sapporo, Japan.
Department of Gastroenterology, National Hospital Organization Hokkaido Medical Center, Sapporo, Japan.
出版信息
Oncologist. 2021 Oct;26(10):e1675-e1682. doi: 10.1002/onco.13838. Epub 2021 Jun 21.
LESSONS LEARNED
Because S-1 is orally administered, OX-IRIS does not necessitate the continuous infusion of 5-FU and is more convenient. The recommended dose of OX-IRIS was determined to be level -1 (oxaliplatin, 65 mg/m ; irinotecan, 100 mg/m ; S-1, 80 mg/m ), which has manageable safety and promising anticancer activities.
BACKGROUND
OX-IRIS is a new combination therapy of oxaliplatin, irinotecan, and S-1 for unresectable pancreatic ductal adenocarcinoma (PDAC), which may be beneficial because S-1 is administered orally and continuous infusion of 5-fluorouracil (5-FU) is not needed.
METHODS
Patients who had not received prior therapy for unresectable PDAC were enrolled. Adenocarcinoma or adenosquamous histology was required. Oxaliplatin and irinotecan were administered on days 1 and 15; S-1 was administered orally twice a day on days 1-14, followed by 14 days of rest (one cycle). Primary endpoints were dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). Secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).
RESULTS
In level 0 (oxaliplatin, 85 mg/m ; irinotecan, 100 mg/m ; S-1, 80 mg/m ), two of five patients experienced DLT. In level -1 (oxaliplatin, 65 mg/m ; irinotecan, 100 mg/m ; S-1, 80 mg/m ), DLT could not be evaluated in two of eight patients because one cycle was not completed; one of the remaining six patients experienced DLT. Anemia, thrombocytopenia, fatigue, nausea, anorexia, diarrhea, and peripheral sensory neuropathy were seen frequently in levels 0 and -1. ORR was 30% in levels 0 and -1. Median progression-free survival and median overall survival were 4.1 months (95% confidence interval [CI], 0.0-8.9 months) and 13.7 months (95% CI, 4.8-22.6 months), respectively.
CONCLUSION
MTD of OX-IRIS therapy was estimated to be level 0, and the recommended dose (RD) for future trial was level -1.
经验教训
由于 S-1 是口服给药，因此 OX-IRIS 不需要持续输注 5-FU，并且更加方便。确定 OX-IRIS 的推荐剂量为 1 级（奥沙利铂，65mg/m 2 ；伊立替康，100mg/m 2 ；S-1，80mg/m 2 ），其安全性可管理，且具有有前景的抗癌活性。
背景
OX-IRIS 是一种新的奥沙利铂、伊立替康和 S-1 的联合治疗方案，用于不可切除的胰腺导管腺癌（PDAC），这可能是有益的，因为 S-1 是口服给药，不需要持续输注 5-氟尿嘧啶（5-FU）。
方法
招募未接受过不可切除 PDAC 治疗的患者。需要腺癌或腺鳞癌组织学。奥沙利铂和伊立替康于第 1 天和第 15 天给药；S-1 于第 1-14 天每天口服两次，随后休息 14 天（一个周期）。主要终点是剂量限制毒性（DLT）和最大耐受剂量（MTD）。次要终点是安全性、总缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。
结果
在 0 级（奥沙利铂，85mg/m 2 ；伊立替康，100mg/m 2 ；S-1，80mg/m 2 ）中，5 名患者中有 2 名出现 DLT。在 1 级（奥沙利铂，65mg/m 2 ；伊立替康，100mg/m 2 ；S-1，80mg/m 2 ）中，由于一个周期未完成，8 名患者中有 2 名无法评估 DLT；其余 6 名患者中的 1 名出现 DLT。0 级和 1 级患者经常出现贫血、血小板减少、疲劳、恶心、厌食、腹泻和周围感觉神经病变。0 级和 1 级的总缓解率为 30%。中位无进展生存期和中位总生存期分别为 4.1 个月（95%置信区间[CI]，0.0-8.9 个月）和 13.7 个月（95%CI，4.8-22.6 个月）。
结论
OX-IRIS 治疗的 MTD 估计为 0 级，未来试验的推荐剂量（RD）为 1 级。
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