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Cediranib showed anticancer activity in recurrent epithelial ovarian, fallopian tube and peritoneal cancer
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Data from a phase-2 trial indicated a 30% clinical benefit rate among 46 patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer who were treated with once daily cediranib, an oral tyrosine kinase inhibitor of several vascular endothelial growth factor receptors.
Enrolled patients had measurable cancer via Response Evaluation Criteria in Solid Tumors (RECIST) and had been administered up to two prior lines of therapy for recurrence.
Although no patients had complete response as measured with RECIST criteria or Gynecological Cancer Intergroup modified CA-125 response, partial response was observed in eight patients, and six patients experienced stable disease for more than 16 weeks. Mean PFS was 4.6 months; mean OS was 16.3 months.
Initial dosing was started at 45 mg daily, but toxicities and failure to tolerate cediranib (AZD2171, AstraZeneca) were observed in the majority of the first 11 patients treated, prompting the researchers to lower the dose to 30 mg in eight of those patients.
Doses were also reduced in 21 of the 35 patients who were assigned 30 mg of cediranib daily, with the most common reasons being fatigue, diarrhea, proteinuria, hypertension and mucositis.
Toxicities observed in this study were similar to those observed with other tyrosine kinase inhibitors, according to the researchers, with the most common including diarrhea (91%), fatigue (89%), hypertension (83%), hypothyroidism (56%), mucositis (50%), voice changes (46%), nausea (41%), headache (41%), abdominal pain (30%), proteinuria (24%) and vomiting (24%).
Additional studies are currently under way to explore cediranib’s potential role in other phases of treatment, including its efficacy when combined with chemotherapy and as a maintenance drug for patients with platinum-sensitive recurrent epithelial ovarian cancer.
“Randomized trials of these drugs should include patient-reported outcomes to assess effects on quality of life,” the researchers wrote.
Matulonis UA. J Clin Oncol. 2009;doi:10.1200/JCO.2009.23.2777.