SAFETY AND TOLERABILITY OF VANDETANIB IN JAPANESE PATIENTS WITH MEDULLARY THYROID CANCER: A PHASE I/II OPEN-LABEL STUDY.
OBJECTIVE
In a phase III trial, Western patients with medullary thyroid cancer (MTC) treated with the oral multikinase inhibitor vandetanib showed significantly improved progression-free survival (PFS) and objective response rate (ORR) compared with placebo. The biology of MTC and pharmacokinetics (PK) are similar for Japanese and Western patients; therefore, similar clinical benefit is anticipated in the Japanese population. This study evaluated the safety and tolerability of vandetanib in Japanese patients with unresectable locally advanced or metastatic MTC.


METHODS
This was a phase I/II, open-label, nonrandomized study. Patients received vandetanib (300 mg daily) until objective disease progression. The primary endpoints were safety and tolerability. Secondary endpoints included efficacy and PK. Final data analysis was conducted once all patients with measurable baseline disease had been followed to progression, or for 56 weeks.


RESULTS
Fourteen patients received vandetanib. All patients experienced at least one adverse event (AE), and 7 patients (50%) experienced grade ≥3 AEs. Common AEs included diarrhea (79%), hypertension (64%), and rash (43%). Four patients reported a total of five serious AEs (SAEs). Eleven patients (79%) had dose interruptions, and 8 patients (57%) had dose reductions. One patient discontinued treatment because of an SAE (interstitial lung disease). No patients met the prespecified criterion for QTc prolongation. The ORR was 38% and PFS at 12 months was 85%.


CONCLUSIONS
Safety and efficacy data were comparable to those previously reported, and AEs were generally manageable by standard clinical practice or dose modifications. Overall, vandetanib was considered to be beneficial for Japanese MTC patients.


BACKGROUND
AE = adverse event CI = confidence interval Css,max= maximum steady-state plasma concentration DCR = disease control rate EGFR = epidermal growth factor receptor ILD = interstitial lung disease MTC = medullary thyroid cancer ORR = objective response rate PFS = progression-free survival PK = pharmacokinetics RECIST = Response Evaluation Criteria in Solid Tumors RET = re-arranged during transfection SAE = serious adverse event VEGFR = vascular endothelial growth factor receptor.
Keita
K
Uchino
Masato
M
Komoda
Junichi
J
Tomomatsu
Takahiro
T
Okamoto
Kiyomi
K
Horiuchi
Akihito
A
Tsuji
Yasuhiro
Y
Ito
Takuya
T
Todo
Ki
K
Rito
Shunji
S
Takahashi
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D010880:Piperidines; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; C452423:vandetanib