Efficacy observation of albumin-bound paclitaxel combined with S1, sequential and alternate gemcitabine combined with oxaliplatin in the first-line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC): A single-arm, prospective study.
Authors: Li Zhiwei , Li Qingwei , Fan Xiaona , Wang Dan , Lou Changjie , Xu Haitao , Zhan Chao , Dong Yuandi , Ma Zhigang , Wang Guangyu , Zhang Chunhui , Lu Haibo , Zheng Tongsen , Zhang Yanqiao 
Published: January 2021

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Background:Chemotherapy is effective in mPDAC but the effect is not satisfactory. Alternate sequential treatment appears to be feasible and effective, with manageable toxicities and decreased neurotoxicity. Similar studies have not been carried out in China. Therefore, we evaluated the efficacy and safety of albumin-bound paclitaxel combined with S1, sequential and alternate gemcitabine combined with oxaliplatin in the first-line treatment of patients with mPDAC. Methods:Based on an expected 6-month PFS rate of 45% and a threshold 6-month PFS rate of 25%, a one-sided exact test is applied setting α = 0.025. The number of patients required for a power of 80% was calculated to be 24. Considering the drop rate of 15%, 30 patients need to be enrolled in the experiment. This open-label, single-arm, prospective study enrolled patients with locally advanced and metastatic pancreatic cancer, who have not received prior chemotherapy regimens and radiation therapy between Jan, 2019 and Dec, 2020. The patient receives the NS regimen first:albumin-bound paclitaxel(125mg/m2) was administered for the first and eighth day by intravenous drip and S1 (40-60 mg)was administered orally twice a day for 2 cycles with 3-week cycle. Then the GEMOX regimen is applied sequentially and alternately: Gemcitabine (1000mg/m2, intravenous infusion for 30 minutes, administration on the first and eighth days) and oxaliplatin (130mg/m2, intravenous injection for 2 hours, administration on the second day) were given for 2 cycles with 3-week cycle. After that, the NS and GEMOX regimen were alternately used again. The treatment was continued until disease progression or unacceptable toxic effects. Results:In this study, 36 eligible patients received the sequential treatment of the above regimen with a median age of 59 years (range 35 to 67 years). 24 patients were eligible for efficacy analysis. Median follow up time was 8.8 months. 45.8% (11/24) of patients completed 3 alternating (8 cycles) treatment, and 33.3% (8/24) of patients completed 2 alternating (6 cycles) treatment, other patients only completed 1 alternate treatment. 6-month PFS rate was 70.8%(17/24), The median PFS of 24 patients was 8.9 months. The final OS and PFS was not yet achieved. The most common grade 3/4 treatment related AEs were thrombocytopenia (13.33%), granulopenia (8.3%), peripheral nerve toxicity (5.6%), and all adverse reactions could be recovered to less than grade 2 after suspension of medication or reduction of dose. Conclusions: The treatment of albumin-bound paclitaxel combined with S1, sequential and alternate gemcitabine combined with oxaliplatin showed promising efficacy and manageable toxicities in patients with mPDAC, and required more prospective patients to be enrolled. Clinical trial information: ChiCTR1900024867.