Download response_to_lenvatinib_in_progressive_metastatic_paraganglioma

RESPONSE TO LENVATINIB IN
PROGRESSIVE METASTATIC
PARAGANGLIOMA
Sina Jasim,M.D.1, Chintakuntlawar, Ashish,M.D.PhD 2, Keith Bible, M.D.PhD 2
1Division
of Endocrinology, 2Division of Medical Oncology
Mayo Clinic, Rochester, MN
BACKGROUND:
•
Paragangliomas are rare, sometimes malignant, vascular endocrine tumors that highly
express vascular endothelium growth factor (VEGF).
•
Anti-angiogenic agents may thus play a role in the treatment of these tumors.
•
We report a dramatic clinical response to the oral VEGFR 1-3 and multi-kinase inhibitor
lenvatinib.
CASE DESCRIPTION
•
A 49-year-old female with longstanding metastatic pelvic PGL with SDHB (p.V140F--c.418G>T)
mutation.
•
Multiple surgical resections, chemotherapeutic regimens (etoposide, cisplatin;
cyclophosphamide, doxorubicin, cisplatin; cyclophosphamide, vincristine, dacarbazine) as well
as with local therapies at metastatic sites (radiation, cryoablation).
•
She benefited from pazopanib (VEGFR and multi-kinase inhibitor) for ~2 years, attaining a
partial response, but ultimately progressed with the development of hypertension.
•
CT scans of chest, abdomen and pelvis showed progression of hilar, pelvic and peritoneal
metastatic lymphadenopathy.
•
Laboratory values: Metanephrine level < 0.20 nmol/L (<0.50 nmol/L),nor-metanephrines 5.7
nmol/L (<0.90 nmol/L), Chromogranin A 1018 ng/mL (< 93 ng/mL)
•
Radiotherapy to the right hilar lymphadenopathy (4000 cGy, 10 fractions; irradiated disease
progress despite radiotherapy)
•
Alpha and beta blockade (phenoxybenzamine and atenolol) as well as calcium channel
blockers started to maintain controlled blood pressure while initiating lenvatinib (24 mg daily).
RESULTS
• Within 48 hours of lenvatinib initiation, she had dramatic nodal clinical tumor
regression associated with fever. Work up revealed no infectious source for
fever.
• Laboratory evaluation were consistent with mild tumor lysis syndrome.
• Biochemical response (Figure 1)
• Follow up imaging showed interval decreases in hilar and retroperitoneal
adenopathy and a confirmed RECIST response (Figure 2)
• Side effects prominently included fatigue.
RESULTS
Figure 1A: Chromogranin A level
Figure 1B: Normetanephrine level
Chromogranin A (ng/mL)
1200
Normetanephrine (nmol/L)
1018
6
1000
5.7
5
800
4
600
400
200
3
3
306
93
93
280
2
93
1
1.7
0.9
0.9
0.9
1.1
Jul-15
Aug-15
Sep-15
Oct-15
0
0
Jul-15
Aug-15
Patient
Sep-15
Reference
Oct-15
Patient
Reference
FIGURE 2: CT CHEST BEFORE AND ON THERAPY
DISCUSSION/CONCLUSION
• Like other VEGFR-targeted kinase inhibitors, lenvatinib may represent a
promising drug for further development in treating refractory metastatic
paraganglionoma.
• Systemic therapies, like multi-kinase inhibitors , can induce hypertensive
episodes, which require close monitoring, as well as have potential to induce
tumor lysis-like phenomena.
• Special care must be taken to respond emergently to minimize patient risks in
the event of rapid tumor regression.