A phase II study of sunitinib in patients with locally advanced or metastatic cervical carcinoma: NCIC CTG Trial IND.184.
OBJECTIVE
Vascular endothethial growth factor (VEGF) and stem cell factor (c-KIT) signaling may play a role in the development and progression of cervical carcinoma. Sunitinib malate is an oral, multi-targeted tyrosine kinase inhibitor that inhibits receptors for VEGF, c-Kit and platelet-derived growth factor. This multi-centre phase II study was performed to evaluate the activity of sunitinib in women with locally advanced or metastatic cervical carcinoma who had received up to one prior line of chemotherapy for advanced disease.


METHODS
Sunitinib, 50 mg/day, was administered in 6-week cycles (4 weeks on followed by 2 weeks off treatment). The primary endpoint was the objective response rate.


RESULTS
Sixteen (84%) of 19 patients enrolled had stable disease (median duration 4.4 months, 2.3-17 months), but no objective response was observed. Median time to progression was 3.5 months (range, 2.7-7.0 months). Four patients had fistulae develop on study treatment and an additional patient developed a fistula 3.5 months after discontinuation of therapy. All five patients had received either prior chemoradiation or radiation.


CONCLUSIONS
A higher rate of fistula formation (26.3%) was observed than would be expected and is of concern. Sunitinib has insufficient activity as a single agent in cervical cancer to warrant further investigation.
Mackay
Helen J
HJ
Department of Medical Oncology, Princess Margaret Hospital, University of Toronto, Ontario M5G 2M9, Canada. helen.mackay@uhn.on.ca
Tinker
Anna
A
Winquist
Eric
E
Thomas
Gillian
G
Swenerton
Kenneth
K
Oza
Amit
A
Sederias
Joana
J
Ivy
Percy
P
Eisenhauer
Elizabeth A
EA
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib