A phase II study of cediranib, an oral VEGF inhibitor, in previously untreated patients with metastatic or recurrent malignant melanoma
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Purpose A two stage multi-institution Phase II study was undertaken by the Princess Margaret Hospital Consortium to evaluate the efficacy and toxicity of oral cediranib, an inhibitor of vascular endothelial growth factor receptors 1 and 2, in patients with previously untreated advanced malignant melanoma. Patients and Methods Between May 2006 and April 2008, 24 patients (median age 65 years) with advanced malignant melanoma were treated with oral cediranib. Cediranib was given on a continuous, oral once daily schedule of 45 mg, on a 28 day cycle. Results Of the 17 patients evaluable for response, there was stable disease in 8 patients, and progressive disease in 9 patients, with no objective responses seen. Only 2 patients had stable disease >/= 6 months, thus the study was terminated at the end of stage 1 accrual. The overall median survival was 9.9 months, and the median time to progression was 3.5 months. The most frequent non-hematologic adverse events were hypertension (78 %), fatigue (69 %), diarrhea (69 %) and anorexia and nausea (each 57 %). Conclusions Although 2 patients had stable disease at 6 months, the short median time to progression and lack of any objective responses indicate that single agent cediranib at this dose and schedule is not sufficiently active to warrant study continuation.
KeywordsMetastatic melanoma Cediranib Phase II trial First line therapy Vascular endothelial growth factor (VEGF)
This study (PHL-038/NCI 7137) is conducted by the Princess Margaret Hospital Phase II Consortium with support from US National Cancer Institute Grant #HHSN261201100032C.
Compliance with ethical standards
Conflict of interest
The authors declare they have no conflict of interest.
- 5.Therasse P, Arbuck S, Eisenhauer EA, et al. (2000) New guidelines to evaluate the response to treatment in solid tumors; European organization for research and treatment of cancer, national cancer institute of the United States, national cancer institute of Canada. J Nat Cancer Inst 92:205–216CrossRefPubMedGoogle Scholar
- 7.Mitchell CL, O’Connor JP, Roberts C, et al. (2011) A two-part phase II study of cediranib in patients with advanced solid tumours: the effect of food on single-dose pharmacokinetics and an evaluation of safety, efficacy and imaging pharmacodynamics. Cancer Chemother Pharmacol 68:631–641CrossRefPubMedGoogle Scholar
- 11.Goodwin R, Ding K, Seymour L, et al. (2010) Treatment-emergent hypertension and outcomes in patients with advanced non-small-cell lung cancer receiving chemotherapy with or without the vascular endothelial growth factor receptor inhibitor cediranib: NCIC clinical trials group study BR24. Ann Oncol 21:2220–2226CrossRefPubMedGoogle Scholar
- 14.Hauschild A, Agarwala SS, Trefzer U, et al. (2009) Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. J Clin Oncol 27:2823–2830CrossRefPubMedGoogle Scholar