Background
Nitric oxide donors decreased cell survival in vitro and tumor load in vivo in models
of rectal cancer subjected to ionizing radiation. Nitroglycerin (NTG) transdermal
patches, added to chemotherapy, have been shown to improve outcomes in lung cancer
patients.
Methods
This open-label, nonrandomized, multicohort, dose escalation, phase I trial had a
primary endpoint to evaluate the safety, tolerability, feasibility, dose-limiting
toxicity and maximum tolerated dose of topical NTG in addition to 5-fluorouracil and
radiation therapy for neoadjuvant treatment of locoregionally advanced operable rectal
cancer. The secondary endpoint was rate of pathologic complete response (pCR). Patients
were assigned to 3 sequential cohorts of escalating dose levels of commercially available
NTG patches (0.2, 0.4, and 0.6 mg/h), each cohort was intended to consist of 3 patients.
Results
Thirteen patients were enrolled in the trial as specified in the dose escalation protocol.
They were all male with a median age of 59.4 ± 2.5 (SEM) years. The observed toxicities
were mild to moderate and manageable. Four patients developed asymptomatic grade 3
lymphopenia during the chemoradiation that resolved promptly upon completion. One
patient had a non-ST segment elevation MI and 1 patient developed diarrhea. None of
these toxicities were attributed to NTG except for 1 patient who developed a grade
3 headache. This required an additional group of patients at the same dose and no
other patient experienced headaches. pCR was 17%.
Conclusion
NTG patches are well-tolerated and it is feasible to proceed with a phase II trial
at the maximum dose examined (0.6 mg/h).
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Article info
Publication history
Published online: May 08, 2015
Accepted:
April 10,
2015
Identification
Copyright
Published by Elsevier Inc.
