Efficacy and safety of single agent or combination adjuvant chemotherapy in elderly patients with colon cancer: a Canadian cancer institute experience.

BACKGROUND: The pattern of adjuvant chemotherapy (AC) use, toxicity profile, and survival benefit in elderly patients with colon cancer (CC) is unclear. We sought to (1) determine whether patients ≥ 65 years with stage III CC were offered single-agent or combination AC, (2) evaluate the reason for selecting single-agent versus combination AC, (3) evaluate the toxicity profile of single-agent and combination AC in the elderly, and (4) determine whether a survival benefit exists for elderly patients receiving combination AC. PATIENTS AND METHODS: A retrospective analysis of records of patients ≥ 65 years diagnosed with stage III CC from 2004 to 2010 was performed to identify baseline characteristics, AC protocols, toxicity, dose intensity, and survival. RESULTS: Two hundred sixty-eight patients ≥ 65 years were diagnosed and treated with AC from 2004 to 2010. Of these patients, 178 were treated with single-agent AC and 90 were treated with combination AC. The most common reasons for choosing single-agent AC were patient preference, comorbidities, and lack of drug coverage. For each year over 65 years, the odds of receiving combination over single-agent AC decreased by 22%. There were more dose delays, dose reductions, and early chemotherapy discontinuation in the combination AC group because of hematologic toxicity. The 5-year overall survival (OS) was 73% in patients who received single-agent AC compared with 84% in those who received combination AC. There was no difference in cancer-related deaths between the groups. CONCLUSION: In elderly patients treated with AC for stage III CC, single-agent AC is used more frequently than combination AC, based on age, comorbidities, and patient choice. Toxicity with combination AC in elderly patients is high. No survival benefit was seen with combination AC over single-agent AC.

Atypical reversible posterior leukoencephalopathy syndrome (RPLS) induced by cediranib in a patient with metastatic rectal cancer.

BACKGROUND: Reversible posterior leukoenecphalopathy syndrome (RPLS) is a rare clinicoradiologic syndrome characterized by neurologic symptoms such as seizures, headaches, visual abnormalities, confusion and encephalopathy, accompanied by vasogenic edema of posterior white matter seen on neuroimaging. It has been reported in association with many anti-angiogenic therapies, including bevacizumab, sunitinib, sorafenib, pazopanib and regorafenib. Cediranib is a potent, orally available small molecule tyrosine kinase inhibitor with anti-angiogenic activity, which has been shown to have activity against various solid tumors. CASE REPORT: We present a case of a 65 year old male with metastatic adenocarcinoma of the rectum who received cediranib as part of a phase I clinical trial. He developed confusion and fluctuations in his level of consciousness. MRI of the brain revealed diffuse low level T2 signal abnormality in the cerebral peduncles, pons, and medulla and patchy T2 signal in both thalami, consistent with RPLS. With conservative management, including tight blood pressure control, his symptoms improved and MRI findings resolved. CONCLUSION: RPLS is a rare, but serious, clinicoradiologic syndrome which has been described as an adverse effect of many anti-angiogenic agents and should also be considered in patients on cediranib who present with neurologic symptoms along with vasogenic edema seen on MRI. If RPLS is suspected, cediranib should be discontinued and blood pressure should be aggressively controlled.