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Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma.

ABSTRACT: Nab-paclitaxel-gemcitabine combination significantly improved overall survival over gemcitabine in metastatic pancreatic adenocarcinoma. A phase 1b trial was performed (ClinicalTrials.gov number, NCT01730222) to determine the recommended phase 2 dose (RP2D) of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine at fixed dose (800, 30, and 1250?mg?m(-2) every 2?weeks, respectively; PAXG regimen).Nab-paclitaxel doses were escalated from 100 (level one) to 125 (level two) and 150?mg?m(-2) (level three) every 2?weeks in cohorts of 3-6 patients with pathologically confirmed unresectable or borderline resectable pancreatic adenocarcinoma.Between Dec 2012 and Apr 2014, 24 patients were enroled (3 at level one, 5 at level two, 16 at level three) and received 117 cycles of PAXG. No dose-limiting toxicity occurred and level three was the RP2D. At this dose, nab-paclitaxel dose-intensity was 91%. Worse per patient grade 3/4 toxicity were neutropenia 25/31%; fatigue 19%; anaemia and hand-foot syndrome 12%, nausea 6%, and febrile neutropenia 6%. A partial response (PR) was observed in 16 (67%) and stable disease (SD) in 8 patients (33%). Among 21 patients with a baseline positive positron emission tomography (PET) scan, a complete metabolic response was observed in 9 (43%), PR in 10 (48%), SD in 2. CA19-9 decreased by ?49% in all the 19 patients with elevated basal value. Six patients were resected after chemotherapy. Progression-free survival at 6?months (PFS-6) was 96%.The RP2D of nab-paclitaxel in the PAXG regimen was 150?mg?m(-2) every 2?weeks. The preliminary results are promising and warrant further exploration.

SUBMITTER: Reni M

PROVIDER: S-EPMC4973162 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma.

Reni Michele M Balzano Gianpaolo G Zanon Silvia S Passoni Paolo P Nicoletti Roberto R Arcidiacono Paolo Giorgio PG Pepe Gino G Doglioni Claudio C Fugazza Clara C Ceraulo Domenica D Falconi Massimo M Gianni Luca L

British journal of cancer 20160712 3

<h4>Background</h4>Nab-paclitaxel-gemcitabine combination significantly improved overall survival over gemcitabine in metastatic pancreatic adenocarcinoma. A phase 1b trial was performed (ClinicalTrials.gov number, NCT01730222) to determine the recommended phase 2 dose (RP2D) of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine at fixed dose (800, 30, and 1250 mg m(-2) every 2 weeks, respectively; PAXG regimen).<h4>Methods</h4>Nab-paclitaxel doses were escalated from 10 ...[more]

PMID: 27404453

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Project description:BackgroundNeoadjuvant chemoradiotherapy can provide downstaging and improve margin negativity for borderline resectable and resectable pancreatic adenocarcinoma [(B)RPC]. Little is known about the relative efficacy of capecitabine (CAPE)-based vs. gemcitabine (GEM)-based 3-week chemoradiation (3WCRT) with 36 Gy in 15 fractions. This study aimed to compare the odds of achieving surgical resection, time to progression (TTP), and overall survival (OS) of patients treated with 3WCRT with concurrent CAPE versus GEM.MethodsA retrospective cohort study was conducted, examining medical records from a single center for patients with (B)RPC treated with 3WCRT between 1/2009-12/2020. Odd ratios (OR) of achieving surgical resection were estimated using logistic regression for univariable and multivariable analyses. Median TTP (mTTP) and median OS (mOS) were estimated using the Kaplan-Meier method. Cox proportional hazards analysis was conducted to estimate hazard ratios (HR) of progression and survival in univariable and multivariable analyses.ResultsThirty-one patients were included in the analysis. Twenty-two (71%) patients were treated with CAPE, while 9 (29%) were treated with GEM. All patients in the GEM group were borderline resectable, vs. 18 (82%) patients in the CAPE group, P=0.30. Nineteen (86%) patients in the CAPE group were treated with neoadjuvant FOLFIRINOX, vs. 4 (44%) patients in the GEM group, P=0.03. The CAPE group had higher odds of achieving surgical resection [OR =9.33; 95% confidence interval (CI): 1.50-58.20]. Adjusting for covariates, the odds of achieving surgical resection were still statistically higher in the CAPE group vs. the GEM group (OR =25.34; 95% CI: 1.14-563.72). The CAPE group had superior mTTP compared to the GEM group (15.4 months, 95% CI: 4.9-71.1 vs. 4.0 months, 95% CI: 0.4-14.5; P=0.01), corresponding to a hazard ratio of 0.33 (95% CI: 0.14-0.81). Adjusting for covariates this effect persisted; the adjusted hazard ratio (AHR) for progression was 0.24 (95% CI: 0.08-0.77). Cox proportional hazards analysis also demonstrated that the CAPE group had superior OS compared to the GEM group in unadjusted (HR =0.13; 95% CI: 0.04-0.40) and adjusted models (HR =0.13, 95% CI: 0.03-0.52).ConclusionsFor neoadjuvant 3WCRT, this hypothesis-generating study suggests concurrent CAPE may be a more effective radiosensitizer than GEM for patients with (B)RPC.

Project description:Our study aimed to compare the efficacy and safety of nab-paclitaxel plus cisplatin (AP) with nab-paclitaxel plus gemcitabine (AG) in patients with metastatic breast cancer (MBC). We collected data from two single-arm, phase II MBC studies. In NCT01149798, seventy-three MBC patients received 125 mg/m2 nab-paclitaxel on days 1, 8 and 15 followed by 75 mg/m2 cisplatin on day 1 of a 28-day cycle. In NCT01550848, eighty-four MBC patients received 125 mg/m2 nab-paclitaxel and 800 mg/m2 gemcitabine on days 1, 8, and 15 of a 28-day cycle. The endpoints were the overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety profiles of these regimens. Among the 157 patients included, the ORR were 67.1% and 52.4% for the AP and AG arms, respectively (odds ratio [OR] = 0.246; hazard ratio [HR] = 1.485; 95% confidence interval [CI], 0.762-2.985). After median follow-up periods of 26.3 and 23.3 months in the AP and AG arms, the median PFS were 9.8 months (95%CI, 8.1-11.6) and 8.1 months (95%CI, 6.8-9.4), respectively, while the median OS were 26.9 months (95%CI, 22.4-31.4) and 25.5 months (95%CI, 19.3-31.4), respectively. Neither PFS nor OS adjusted for the number of metastases, occurrence of liver metastasis and chemotherapeutic lines differed significantly between the two arms (PFS:HR = 0.769; 95%CI, 0.541-1.092; p = 0.142; OS:HR = 0.686; 95%CI, 0.426-1.104; p = 0.120). However, PFS was significantly better with AP than with AG in metastatic triple-negative breast cancer (mTNBC) patients (HR = 0.308; 95%CI, 0.129-0.732; p = 0.008). Adverse events were more common with AP than with AG, except for edema and myalgia. Both regimens showed substantial efficacy and were tolerated well in MBC patients. mTNBC who received AP rather than AG showed longer PFS. However, adverse events were more common with AP. Thus, AP may be worth recommending to mTNBC, while AG may be a better alternative for MBC patients with other subtypes.

Dataset Information

Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma.

Publications

Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma.

Similar Datasets

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