TY - JOUR
T1 - Nab-Paclitaxel, Capecitabine, and Radiation Therapy After Induction Chemotherapy in Treating Patients With Locally Advanced and Borderline Resectable Pancreatic Cancer
T2 - Phase 1 Trial and Imaging-based Biomarker Validation
AU - Koay, Eugene J.
AU - Zaid, Mohamed
AU - Aliru, Maureen
AU - Bagereka, Polycarpe
AU - Van Wieren, Arie
AU - Rodriguez, Maria Jovie
AU - Jacobson, Galia
AU - Wolff, Robert A.
AU - Overman, Michael
AU - Varadhachary, Gauri
AU - Pant, Shubham
AU - Wang, Huamin
AU - Tzeng, Ching Wei
AU - Ikoma, Naruhiko
AU - Kim, Michael
AU - Lee, Jeffrey E.
AU - Katz, Matthew HG
AU - Tamm, Eric
AU - Bhosale, Priya
AU - Taniguchi, Cullen M.
AU - Holliday, Emma B.
AU - Smith, Grace L.
AU - Ludmir, Ethan B.
AU - Minsky, Bruce D.
AU - Crane, Christopher H.
AU - Koong, Albert C.
AU - Das, Prajnan
AU - Wang, Xuemei
AU - Javle, Milind
AU - Krishnan, Sunil
N1 - Funding Information:
We gratefully acknowledge support from Celgene for support of the clinical trial. Eugene Koay was supported by the Andrew Sabin Family Fellowship, the Sheikh Ahmed Center for Pancreatic Cancer Research, institutional funds from The University of Texas MD Anderson Cancer Center, the Khalifa Foundation, equipment support by GE Health care and the Center of Advanced Biomedical Imaging, Philips Health care, Cancer Center Support (Core) Grant CA016672 from the National Cancer Institute to MD Anderson, and NIH (U54CA210181, U54CA143837, U01CA200468, U01CA196403, U01CA214263, R01CA221971, R01CA248917, and R01CA218004).
Funding Information:
We gratefully acyknowledge support from Celgene for support of the clinical trial. Eugene Koay was supported by the Andrew Sabin Family Fellowship, the Sheikh Ahmed Center for Pancreatic Cancer Research, institutional funds from The University of Texas MD Anderson Cancer Center, the Khalifa Foundation, equipment support by GE Health care and the Center of Advanced Biomedical Imaging, Philips Health care, Cancer Center Support (Core) Grant CA016672 from the National Cancer Institute to MD Anderson, and NIH (U54CA210181, U54CA143837, U01CA200468, U01CA196403, U01CA214263, R01CA221971, R01CA248917, and R01CA218004). Disclosures: M.O. is consulting for Merck Sharp & Dohme Corp, AbbVie, Agilvax, and Acrotech Biopharma and is a Scientific/Advisory committee member at Takeda Pharmaceuticals (Japan). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher Copyright:
© 2022 The Authors
PY - 2022/11/1
Y1 - 2022/11/1
N2 - Purpose: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response. Methods and Materials: Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m2) with concurrent capecitabine and RT in cohort sizes of 3 starting at the lowest dose. Dose limiting toxicity was defined as grade 3 or higher toxicity. Patients were restaged 4 to 6 weeks post-CRT completion, and surgical resection was offered to those with stable/responsive disease. We scored the tumor interface response (IR) postchemotherapy and post-CRT into type I (remained/became more defined) and type II (became less defined). Overall survival (OS) and progression-free survival (PFS) from time of CRT were estimated using Kaplan-Meier method. P ≤ .05 was considered significant. Results: Twenty-three patients started and finished on protocol (LAPC = 14, BRPC = 9). No grade 3 and 4 toxicities were reported in level 1 (n = 3) or level 2 (n = 3) initial groups. Two patients in the initial level 3 group developed dose limiting toxicity, establishing level 2 dose as the maximal tolerated dose. Level 2 group was expanded for additional 15 patients (for a total of 23 on trial), 5 of whom developed grade 3 toxicities. Seven patients underwent surgical resection. Median OS and PFS were 21.2 and 8.1 months, respectively. Type I IR was associated with better OS (P = .004) and PFS (P = .03) compared with type II IR. Conclusions: We established the maximum tolerated dose for nab-paclitaxel in a consolidative CRT regimen for pancreatic ductal adenocarcinoma. Preliminary efficacy results warrant phase 2 trial evaluation. IR may be used for personalized treatment.
AB - Purpose: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response. Methods and Materials: Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m2) with concurrent capecitabine and RT in cohort sizes of 3 starting at the lowest dose. Dose limiting toxicity was defined as grade 3 or higher toxicity. Patients were restaged 4 to 6 weeks post-CRT completion, and surgical resection was offered to those with stable/responsive disease. We scored the tumor interface response (IR) postchemotherapy and post-CRT into type I (remained/became more defined) and type II (became less defined). Overall survival (OS) and progression-free survival (PFS) from time of CRT were estimated using Kaplan-Meier method. P ≤ .05 was considered significant. Results: Twenty-three patients started and finished on protocol (LAPC = 14, BRPC = 9). No grade 3 and 4 toxicities were reported in level 1 (n = 3) or level 2 (n = 3) initial groups. Two patients in the initial level 3 group developed dose limiting toxicity, establishing level 2 dose as the maximal tolerated dose. Level 2 group was expanded for additional 15 patients (for a total of 23 on trial), 5 of whom developed grade 3 toxicities. Seven patients underwent surgical resection. Median OS and PFS were 21.2 and 8.1 months, respectively. Type I IR was associated with better OS (P = .004) and PFS (P = .03) compared with type II IR. Conclusions: We established the maximum tolerated dose for nab-paclitaxel in a consolidative CRT regimen for pancreatic ductal adenocarcinoma. Preliminary efficacy results warrant phase 2 trial evaluation. IR may be used for personalized treatment.
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U2 - 10.1016/j.ijrobp.2022.06.089
DO - 10.1016/j.ijrobp.2022.06.089
M3 - Article
C2 - 35863672
AN - SCOPUS:85136241327
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
SN - 0360-3016
ER -