A phase I study of pazopanib in combination with escalating doses of 131I in patients with well-differentiated thyroid carcinoma borderline refractory to radioiodine

This trial was conducted to evaluate the ability of pazopanib to overcome therapeutic 131I resistance. This phase 1 trial assesses the combination of pazopanib and escalating doses of radioiodine (131I) in patients with recurrent or metastatic thyroid cancer that are borderline or relatively iodine...

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Bibliographic Details
Published in:PloS one 2017-06, Vol.12 (6), p.e0178325-e0178325
Main Authors: Chow, Laura Q, Santana-Davila, Rafael, Pantel, Austin, Roth, Mara, Anderson, Leslie N, Failor, Alan, Doot, Robert, Mankoff, David
Format: Article
Language:English
Subjects:
Adult
Aged
Antineoplastic Agents - therapeutic use
Arrhythmia
Biology and Life Sciences
Bone marrow
Cancer
Cancer therapies
Clinical trials
Combined Modality Therapy
Computed tomography
Dosimetry
Drug dosages
Effectiveness
Endocrinology
Fatalities
Fatigue
Female
Heart diseases
Humans
Inhibitor drugs
Iodine
Iodine Radioisotopes - administration & dosage
Kinases
Male
Medical research
Medicine
Medicine and Health Sciences
Metastases
Metastasis
Middle Aged
Nuclear medicine
Oncology
Patients
Physical Sciences
Positron emission
Pyrimidines - administration & dosage
Pyrimidines - therapeutic use
Quality
Radiation therapy
Research and Analysis Methods
Sulfonamides - administration & dosage
Sulfonamides - therapeutic use
Survival
Targeted cancer therapy
Therapy
Thyroid
Thyroid cancer
Thyroid carcinoma
Thyroid Neoplasms - drug therapy
Thyroid Neoplasms - radiotherapy
Toxicity
Tumors
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Summary:This trial was conducted to evaluate the ability of pazopanib to overcome therapeutic 131I resistance. This phase 1 trial assesses the combination of pazopanib and escalating doses of radioiodine (131I) in patients with recurrent or metastatic thyroid cancer that are borderline or relatively iodine refractory. Radioiodine uptake scans were assessed post therapy and compared to historical pre-treatment scans. Patients underwent FDG PET/CT before and after the initial pazopanib treatment to identify the impact of pazopanib on the cancer prior to 131I therapy. A dose limiting toxicity (cardiac arrhythmia and grade 3 fatigue) in the first patient in the first cohort prompted expansion to a total of 6 patients. Additional grade 3-4 hematologic toxicity and low accrual in the expanded cohort led to the decision not to pursue further study of the regimen. In patients with measurable disease 4/5 (80%) achieved stable disease. Median progression free survival was 6.7 months. At 3 years of follow up, one patient died due to progressive disease, two are being treated with systemic therapy and 3 continue without requiring subsequent therapy at 15, 27 and 35 months from the last dose of pazopanib. There was no convincing impact of pazopanib on iodine uptake in scans performed pre- and post-therapy compared to scans from historical 131I treatments without pazopanib. Despite a suggestion of therapeutic efficacy, combined pazopanib and 131I resulted in increased toxicity. There was no convincing evidence that the administration of pazopanib improved iodine uptake or retention. ClinicalTrials.gov NCT01413113.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0178325