Nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in treating patients with locally advanced and borderline resectable pancreatic cancer: Phase 1 trial and imaging-based biomarker validation Journal Article
| Authors: | Koay, E. J.; Zaid, M.; Aliru, M.; Bagereka, P.; Van Wieren, A.; Rodriguez, M. J.; Jacobson, G.; Wolff, R. A.; Overman, M.; Varadhachary, G.; Pant, S.; Wang, H.; Tzeng, C. W.; Ikoma, N.; Kim, M.; Lee, J. E.; Katz, M. H.; Tamm, E.; Bhosale, P.; Taniguchi, C. M.; Holliday, E. B.; Smith, G. L.; Ludmir, E. B.; Minsky, B. D.; Crane, C. H.; Koong, A. C.; Das, P.; Wang, X.; Javle, M.; Krishnan, S. |
| Article Title: | Nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in treating patients with locally advanced and borderline resectable pancreatic cancer: Phase 1 trial and imaging-based biomarker validation |
| Abstract: | 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. © 2022 The Authors |
| Keywords: | adult; cancer survival; clinical article; controlled study; aged; cancer surgery; overall survival; clinical trial; intensity modulated radiation therapy; advanced cancer; drug dose reduction; drug efficacy; drug safety; drug withdrawal; capecitabine; gemcitabine; paclitaxel; cancer patient; radiation dose; chemotherapy; follow up; prospective study; biomarkers; progression free survival; computer assisted tomography; phase 2 clinical trial; radiotherapy; alkaline phosphatase; computerized tomography; diagnosis; surgery; phase 1 clinical trial; informed consent; aminotransferase; toxicity; liver hilus; diseases; chemoradiotherapy; induction chemotherapy; phase 1; platelet count; volumetric modulated arc therapy; gross tumor volume; pancreatic ductal carcinoma; pancreatic cancers; organs at risk; response evaluation criteria in solid tumors; distant metastasis free survival; human; male; female; article; x-ray computed tomography; ecog performance status; chemo radiations; interface response; level 2 |
| Journal Title: | International Journal of Radiation Oncology, Biology, Physics |
| Volume: | 114 |
| Issue: | 3 |
| ISSN: | 0360-3016 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2022-11-01 |
| Start Page: | 444 |
| End Page: | 453 |
| Language: | English |
| DOI: | 10.1016/j.ijrobp.2022.06.089 |
| PUBMED: | 35863672 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 October 2022 -- Source: Scopus |
