Dataset Information

Gemcitabine, Docetaxel, Capecitabine, Cisplatin, Irinotecan as First-line Treatment for Metastatic Pancreatic Cancer

ABSTRACT:

Purpose:

Treatment of advanced pancreatic cancer with a single therapeutic at a maximal dose has been largely ineffective at increasing survival. Combination therapies are commonly studied but often limited by toxicity. We previously showed that low-dose multiagent therapy with gemcitabine, docetaxel (taxotere), capecitabine (xeloda), and cisplatin (GTX-C) was safe, well tolerated, and effective (NCT01459614). Here, we hypothesize that adding irinotecan to GTX-C may improve survival with minimal toxicity.

Experimental Design:

Patients with treatment-naïve metastatic pancreatic adenocarcinoma were treated with gemcitabine, docetaxel (taxotere), capecitabine (xeloda), cisplatin, and irinotecan (GTX-CI). Treatment consisted of capecitabine 500 mg twice daily on days 1–14 and gemcitabine 300 to 500 mg/m2, docetaxel 20 mg/m2, cisplatin 15 to 20 mg/m2, and irinotecan 20 to 60 mg/m2 on days 4 and 11 of a 21-day cycle. The primary objective was 9-month overall survival (OS). Secondary objectives included response rate (RR), disease control rate (DCR), progression-free survival (PFS), and OS.

Results:

The regimen was well tolerated. The recommended phase II dose was gemcitabine 500 mg/m2, docetaxel 20 mg/m2, capecitabine 500 mg po bid, cisplatin 20 mg/m2, and irinotecan 20 mg/m2. Median follow-up in phase II was 11.02 months (2.37–45.17). Nine-month OS rate was 57% [95% confidence interval (CI): (41–77)]. RR was 57% [95% CI: (37–75) 50% PR and 7% CR]. DCR was 87% [95% CI: (69–96)]. Median OS and PFS were 11.02 [95% CI: (8.54–21.09)] and 8.34 [95% CI: (6.34–NA)] months, respectively.

Conclusions:

The addition of irinotecan to GTX-C was safe and well tolerated. While the study did not meet its primary objective, the responses were clinically meaningful using a well-tolerated regimen.

Significance:

We aimed to optimize the previously reported efficacious regimen of low-dose multiagent therapy with GTX-C for the treatment of metastatic pancreatic ductal adenocarcinoma by adding irinotecan. The primary objective was not met, but GTX-CI was well tolerated. The RR of 57%, median PFS of 8.3 months, median OS of 11 months, and 36-month OS rate of 19% suggest clinical benefit. Further optimization of this regimen is warranted.

SUBMITTER: Wilbur H

PROVIDER: S-EPMC10461640 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveTo compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma.DesignPhase 3, open label, multicentre, randomised trial.SettingFour hospitals located in China between September 2019 and August 2022.ParticipantsAdults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma.InterventionsPatients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1).Main outcome measuresProgression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population.ResultsThe median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up.ConclusionThe nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival.Trial registrationChinese Clinical Trial Registry ChiCTR1900027112.

Project description:BackgroundThe 5-fuorouracil, oxaliplatin and irinotecan (FOLFOXIRI) regimen is the standard first-line treatment for advanced pancreatic cancer (APC). Capecitabine, an oral prodrug of 5-fluorouracil, offers a more convenient and potentially safer alternative. We evaluated the efficacy and safety of the XELOXIRI regimen (capecitabine, oxaliplatin, irinotecan) in Chinese patients with APC.MethodsThis real-world study evaluated consecutive patients treated with the XELOXIRI regimen as first-line chemotherapy for APC at a national cancer center in China from August 2019 to June 2024. Treatment efficacy was assessed using the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS), and safety was assessed using adverse events (AEs).ResultsFifty-six patients were enrolled (median age, 60 years [range, 33-71]; 35 males, 21 females). Seventeen had locally advanced unresectable disease and 39 had metastatic disease. After a median follow-up of 19.8 months, the ORR was 33.9% (95% confidence interval [CI]: 21.8-47.8), disease control rate was 82.1% (95% CI: 69.6-91.1), and median response duration was 6.2 months (95% CI: 3.6-NA). Six patients with locally advanced disease and one with lung metastasis underwent R0 resection, with one achieving a pathological complete response. Median OS for the entire cohort was 16.2 months (95% CI: 10.6-23.2) and median PFS was 6.3 months (95% CI: 5.3-9.0). OS rates at 6, 12, and 18 months were 92.2%, 56.7%, and 35.6%, respectively; PFS rates were 53.9%, 20.2%, and 6.7%. For those who underwent R0 resection, median OS was not reached and median PFS was 12.3 months (95% CI: 11.9-NA).Treatment-related AEs (TRAEs)occurred in 94.6% of patients, with Grade 3 or higher TRAEs in 44.6%. No Grade 5 TRAEs or treatment-related deaths were observed.ConclusionThe XELOXIRI regimen demonstrated promising efficacy and manageable toxicity in the treatment of APC, providing a practical alternative to FOLFOXIRI, with similar outcomes and easier administration.