CoChat
Sign Up
Cited by 336Pancreatic and Hepatic Oncology ResearchPancreatitis Pathology and TreatmentIntraperitoneal and Appendiceal Malignancies

Phase IB/II randomized study of FOLFIRINOX plus pegylated recombinant human hyaluronidase versus FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: SWOG S1313

Open access
Ramanathan, Ramesh K., McDonough, Shannon L., Philip, Philip A., Hingorani, Sunil R., Lacy, Jill, Kortmansky, Jeremy S., Thumar, Jaykumar, Chiorean, E. Gabriela +7 more·2019·Journal of Clinical Oncology
DOI 10.1200/jco.18.01295PMC PMC6494359
Open this paper in CoChat — free account

Abstract

PURPOSE: Pegylated recombinant human hyaluronidase (PEGPH20) degrades hyaluronan (HA) and, in combination with chemotherapy, prolongs survival in preclinical models. The activity of PEGPH20 with modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) was evaluated in patients with metastatic pancreatic cancer (mPC). MATERIALS AND METHODS: Patients had untreated mPC, a performance status of 0 to 1, and adequate organ function. Tumor HA status was not required for eligibility. After a phase Ib dose-finding study of mFOLFIRINOX plus PEGPH20, the phase II open-label study randomly assigned patients (1:1) to the combination arm or to mFOLFIRINOX alone (n = 138). The primary end point was overall survival (OS). RESULTS: PEGPH20 dosages of 3 µg/kg every 2 weeks were more tolerable than twice-weekly dosages used in the phase I study, so 3 µg/kg every 2 weeks was the phase II dosage. An amendment instituted enoxaparin prophylaxis in the PEGPH20 combination arm as a result of increased thromboembolic (TE) events. The planned interim futility analysis when 35 deaths (of 103 analyzable patients) occurred resulted in an OS hazard ratio (HR) of 2.07 that favored the control arm, and the study was closed to accrual. The treatment-related grade 3 to 4 toxicity was significantly increased in the PEGPH20 combination arm relative to control (odds ratio, 2.7; 95% CI, 1.1 to 7.1). The median OS in the mFOLFIRINOX arm was 14.4 months (95% CI, 10.1 to 15.7 months) versus 7.7 months (95% CI, 4.6 to 9.3 months) in the PEGPH20 combination arm. CONCLUSION: Addition of PEGPH20 to mFOLFIRINOX seems to be detrimental in patients unselected for tumor HA status. This combination caused increased toxicity (mostly GI and TE events) and resulted in decreased treatment duration compared with mFOLFIRINOX alone. The median OS in the mFOLFIRINOX control arm (14.4 months) is, to our knowledge, the longest yet reported and can be considered for patients with good PS.

Integrity signals

Registry

Crossref · 10.1200/jco.18.01295

Cites

23 of 23 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Collagen acts as a signaling molecule by activating discoidin domain receptor signaling in PDAC pathology.

    “Collagen also acts as a signaling molecule, activating discoidin domain receptor signaling that shape multiple roles in PDAC pathology168–171”

    From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [171]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Ramanathan, R. K., McDonough, S. L., Philip, P. A., Hingorani, S. R., Lacy, J., Kortmansky, J. S., Thumar, J., Chiorean, E. G., Shields, A. F., Behl, D., Mehan, P. T., Gaur, R., Seery, T., Guthrie, K. A., & Hochster, H. S.
Affiliations
  • Mayo Clinic Hospital (US)
  • Fred Hutch Cancer Center (US)
  • Wayne State University (US)
  • Yale Cancer Center (US)
  • University of Washington (US)
  • Sutter Cancer Research Consortium, Sacramento, CA
  • Missouri Baptist Medical Center (US)
  • National Cancer Institute (US)
  • University of California, Irvine (US)
  • Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2019-05-01
Volume
37
Issue
13
Pages
1062-1069
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.18.01295
PMC
PMC6494359
OpenAlex
W2917550064
Cited by
336
References
23
Citations by year
2026: 29 · 2025: 31 · 2024: 41 · 2023: 44 · 2022: 56 · 2021: 72 · 2020: 36 · 2019: 23 · 2018: 2 · 2017: 1 · 2014: 1
FWCI
19.51
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Oncology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (UL1TR001863)
  • National Cancer Institute (UG1CA233163, UG1CA189953, U10CA180828, U10CA180846, UG1CA189853, U10CA046368, U10CA180835, UG1CA189848, U10CA180888, UG1CA189830, UG1CA233328, U10CA180819, U10CA013612, U10CA180830, U10CA180826, N01 CA013612, UG1CA189858, UG1CA180830)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
  • Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
Keywords
PEGPH20, FOLFIRINOX, metastatic pancreatic adenocarcinoma, hyaluronan degradation, overall survival, chemotherapy toxicity, thromboembolic events, dose escalation, pancreatic cancer treatment
MeSH terms
Irinotecan, Oxaliplatin, Adenocarcinoma, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Leucovorin, Dose-Response Relationship, Drug, Female, Fluorouracil, Humans, Hyaluronic Acid, Hyaluronoglucosaminidase, Immunohistochemistry, Male, Middle Aged, Neoplasm Metastasis, Pancreatic Neoplasms, Survival Rate

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review