Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases.

BACKGROUND AND PURPOSE: Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors. METHODS: Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) before beginning radiotherapy and one month later. RESULTS: The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms. CONCLUSION: Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings.

Ocular metastases from breast carcinoma.

Intraocular metastases are the most common malignancy of the eye, and the primary cause is breast cancer. This is a retrospective analysis, which reports the clinical experience of eye metastases in 16 patients during the period of January, 1991, to December, 2002, who attended a tertiary referral center in Mexico City. Mean age at diagnosis was 40 yr (range 24-58). Most of patients were initially in clinical stage IIB-IV. Median time from breast cancer diagnosis to development of ocular metastases was 22.5 mo and from metastatic disease to ocular metastases was 10 mo. Ocular symptoms were decrease of visual acuity, ocular pain, nonspecific symptoms, proptosis, and palpebral edema. Three patients had bilateral ocular metastases. Fourteen patients were treated with radiation, and clinical response was documented in 4/15 eyes; ocular pain responded in three patients with this symptom. No ocular enucleations were performed. One patient developed glaucoma. No other major toxicities were documented. Median survival time was 26 mo and 25% of our patients were alive at a maximum follow-up of 90 mo. This entity requires early recognition in order to preserve the visual function and quality of life of patients with breast cancer, since their prognosis has improved in recent years.