Phase 1 study of EUS-guided photodynamic therapy for locally advanced pancreatic cancer

John DeWitt, Kumar Sandrasegaran, Bert O'Neil, Michael House, Nicholas Zyromski, Amikar Sehdev, Susan Perkins, Janet Flynn, Lynne McCranor, Safi Shahda

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background and Aims: Locally advanced pancreatic cancer (LAPC) has a poor prognosis. There are limited data describing the use of photodynamic therapy (PDT) for pancreatic cancer in humans. We hypothesized that EUS-guided PDT for LAPC is safe, technically feasible, and produces a dose- and time-dependent increasing degree of image-defined tumor necrosis. Methods: In a single-center, prospective, dose-escalation phase 1 study, patients with treatment-naïve LAPC received intravenous porfimer sodium (Concordia Laboratories Inc, St Michael, Barbados) followed 2 days later by EUS-PDT. EUS-PDT was performed by puncture with a 19-gauge needle and insertion of a 1.0-cm light diffuser (Pioneer Optics, Bloomfield, Conn) and illumination with a 630-nm light (Diomed Inc, Andover, Mass). A CT scan 18 days after PDT was done to assess for change in pancreatic necrosis. Nab-paclitaxel (125 mg/ m2 intravenously) and gemcitabine (1000 mg /m2 intravenously) were initiated 7 days after CT and given weekly for 3 of 4 weeks (1 cycle) until disease progression or unacceptable toxicity. Results: Twelve patients (mean age, 67 ± 6 years; 8 male) with tumors (mean diameter, 45.2 ± 12.9 mm) in the head and/or neck (8) or body and/or tail (4) underwent EUS-PDT. Compared with baseline imaging, increased volume and percentage of tumor necrosis were observed in 6 of 12 patients (50%) after EUS-PDT. The mean overall increases in volume and percentage necrosis were 10 ± 26 cm3 (P =.20) and 18% ± 22% (P =.016), respectively. After a median follow-up of 10.5 months (range, 1.0-37.4 months), median progression-free (PFS) and overall survival (OS) were 2.6 months (95% confidence interval, 0.7, not estimable) and 11.5 months (95% confidence interval, 1.1, 16.9), respectively. Surgical resection was attempted in 2 patients, and pathology showed a complete response (n = 1) and residual 2-mm tumor (n = 1). There were 8 serious adverse events and none related to EUS or EUS-PDT. Conclusion: EUS-PDT for LAPC appears to be safe and produces measurable imaged-defined tumor necrosis. Phase 2 studies are warranted. (Clinical trial registration number: NCT01770132.)

Original languageEnglish (US)
JournalGastrointestinal Endoscopy
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Photochemotherapy
Pancreatic Neoplasms
Necrosis
gemcitabine
Neoplasms
Barbados
Dihematoporphyrin Ether
Confidence Intervals
Light
Tumor Burden
Lighting
Punctures
Needles
Disease Progression
Tail
Neck
Head
Clinical Trials
Pathology
Survival

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Gastroenterology

Cite this

@article{877d334bc88a47aaa6eced8fb26c8641,
title = "Phase 1 study of EUS-guided photodynamic therapy for locally advanced pancreatic cancer",
abstract = "Background and Aims: Locally advanced pancreatic cancer (LAPC) has a poor prognosis. There are limited data describing the use of photodynamic therapy (PDT) for pancreatic cancer in humans. We hypothesized that EUS-guided PDT for LAPC is safe, technically feasible, and produces a dose- and time-dependent increasing degree of image-defined tumor necrosis. Methods: In a single-center, prospective, dose-escalation phase 1 study, patients with treatment-na{\"i}ve LAPC received intravenous porfimer sodium (Concordia Laboratories Inc, St Michael, Barbados) followed 2 days later by EUS-PDT. EUS-PDT was performed by puncture with a 19-gauge needle and insertion of a 1.0-cm light diffuser (Pioneer Optics, Bloomfield, Conn) and illumination with a 630-nm light (Diomed Inc, Andover, Mass). A CT scan 18 days after PDT was done to assess for change in pancreatic necrosis. Nab-paclitaxel (125 mg/ m2 intravenously) and gemcitabine (1000 mg /m2 intravenously) were initiated 7 days after CT and given weekly for 3 of 4 weeks (1 cycle) until disease progression or unacceptable toxicity. Results: Twelve patients (mean age, 67 ± 6 years; 8 male) with tumors (mean diameter, 45.2 ± 12.9 mm) in the head and/or neck (8) or body and/or tail (4) underwent EUS-PDT. Compared with baseline imaging, increased volume and percentage of tumor necrosis were observed in 6 of 12 patients (50{\%}) after EUS-PDT. The mean overall increases in volume and percentage necrosis were 10 ± 26 cm3 (P =.20) and 18{\%} ± 22{\%} (P =.016), respectively. After a median follow-up of 10.5 months (range, 1.0-37.4 months), median progression-free (PFS) and overall survival (OS) were 2.6 months (95{\%} confidence interval, 0.7, not estimable) and 11.5 months (95{\%} confidence interval, 1.1, 16.9), respectively. Surgical resection was attempted in 2 patients, and pathology showed a complete response (n = 1) and residual 2-mm tumor (n = 1). There were 8 serious adverse events and none related to EUS or EUS-PDT. Conclusion: EUS-PDT for LAPC appears to be safe and produces measurable imaged-defined tumor necrosis. Phase 2 studies are warranted. (Clinical trial registration number: NCT01770132.)",
author = "John DeWitt and Kumar Sandrasegaran and Bert O'Neil and Michael House and Nicholas Zyromski and Amikar Sehdev and Susan Perkins and Janet Flynn and Lynne McCranor and Safi Shahda",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.gie.2018.09.007",
language = "English (US)",
journal = "Gastrointestinal Endoscopy",
issn = "0016-5107",
publisher = "Mosby Inc.",

}

TY - JOUR

T1 - Phase 1 study of EUS-guided photodynamic therapy for locally advanced pancreatic cancer

AU - DeWitt, John

AU - Sandrasegaran, Kumar

AU - O'Neil, Bert

AU - House, Michael

AU - Zyromski, Nicholas

AU - Sehdev, Amikar

AU - Perkins, Susan

AU - Flynn, Janet

AU - McCranor, Lynne

AU - Shahda, Safi

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background and Aims: Locally advanced pancreatic cancer (LAPC) has a poor prognosis. There are limited data describing the use of photodynamic therapy (PDT) for pancreatic cancer in humans. We hypothesized that EUS-guided PDT for LAPC is safe, technically feasible, and produces a dose- and time-dependent increasing degree of image-defined tumor necrosis. Methods: In a single-center, prospective, dose-escalation phase 1 study, patients with treatment-naïve LAPC received intravenous porfimer sodium (Concordia Laboratories Inc, St Michael, Barbados) followed 2 days later by EUS-PDT. EUS-PDT was performed by puncture with a 19-gauge needle and insertion of a 1.0-cm light diffuser (Pioneer Optics, Bloomfield, Conn) and illumination with a 630-nm light (Diomed Inc, Andover, Mass). A CT scan 18 days after PDT was done to assess for change in pancreatic necrosis. Nab-paclitaxel (125 mg/ m2 intravenously) and gemcitabine (1000 mg /m2 intravenously) were initiated 7 days after CT and given weekly for 3 of 4 weeks (1 cycle) until disease progression or unacceptable toxicity. Results: Twelve patients (mean age, 67 ± 6 years; 8 male) with tumors (mean diameter, 45.2 ± 12.9 mm) in the head and/or neck (8) or body and/or tail (4) underwent EUS-PDT. Compared with baseline imaging, increased volume and percentage of tumor necrosis were observed in 6 of 12 patients (50%) after EUS-PDT. The mean overall increases in volume and percentage necrosis were 10 ± 26 cm3 (P =.20) and 18% ± 22% (P =.016), respectively. After a median follow-up of 10.5 months (range, 1.0-37.4 months), median progression-free (PFS) and overall survival (OS) were 2.6 months (95% confidence interval, 0.7, not estimable) and 11.5 months (95% confidence interval, 1.1, 16.9), respectively. Surgical resection was attempted in 2 patients, and pathology showed a complete response (n = 1) and residual 2-mm tumor (n = 1). There were 8 serious adverse events and none related to EUS or EUS-PDT. Conclusion: EUS-PDT for LAPC appears to be safe and produces measurable imaged-defined tumor necrosis. Phase 2 studies are warranted. (Clinical trial registration number: NCT01770132.)

AB - Background and Aims: Locally advanced pancreatic cancer (LAPC) has a poor prognosis. There are limited data describing the use of photodynamic therapy (PDT) for pancreatic cancer in humans. We hypothesized that EUS-guided PDT for LAPC is safe, technically feasible, and produces a dose- and time-dependent increasing degree of image-defined tumor necrosis. Methods: In a single-center, prospective, dose-escalation phase 1 study, patients with treatment-naïve LAPC received intravenous porfimer sodium (Concordia Laboratories Inc, St Michael, Barbados) followed 2 days later by EUS-PDT. EUS-PDT was performed by puncture with a 19-gauge needle and insertion of a 1.0-cm light diffuser (Pioneer Optics, Bloomfield, Conn) and illumination with a 630-nm light (Diomed Inc, Andover, Mass). A CT scan 18 days after PDT was done to assess for change in pancreatic necrosis. Nab-paclitaxel (125 mg/ m2 intravenously) and gemcitabine (1000 mg /m2 intravenously) were initiated 7 days after CT and given weekly for 3 of 4 weeks (1 cycle) until disease progression or unacceptable toxicity. Results: Twelve patients (mean age, 67 ± 6 years; 8 male) with tumors (mean diameter, 45.2 ± 12.9 mm) in the head and/or neck (8) or body and/or tail (4) underwent EUS-PDT. Compared with baseline imaging, increased volume and percentage of tumor necrosis were observed in 6 of 12 patients (50%) after EUS-PDT. The mean overall increases in volume and percentage necrosis were 10 ± 26 cm3 (P =.20) and 18% ± 22% (P =.016), respectively. After a median follow-up of 10.5 months (range, 1.0-37.4 months), median progression-free (PFS) and overall survival (OS) were 2.6 months (95% confidence interval, 0.7, not estimable) and 11.5 months (95% confidence interval, 1.1, 16.9), respectively. Surgical resection was attempted in 2 patients, and pathology showed a complete response (n = 1) and residual 2-mm tumor (n = 1). There were 8 serious adverse events and none related to EUS or EUS-PDT. Conclusion: EUS-PDT for LAPC appears to be safe and produces measurable imaged-defined tumor necrosis. Phase 2 studies are warranted. (Clinical trial registration number: NCT01770132.)

UR - http://www.scopus.com/inward/record.url?scp=85056212212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056212212&partnerID=8YFLogxK

U2 - 10.1016/j.gie.2018.09.007

DO - 10.1016/j.gie.2018.09.007

M3 - Article

JO - Gastrointestinal Endoscopy

JF - Gastrointestinal Endoscopy

SN - 0016-5107

ER -