Radioembolization in combination with systemic chemotherapy as first-line therapy for liver metastases from colorectal cancer.

PURPOSE: To report clinical experience with radioembolization (RE) plus systemic chemotherapy as a first-line treatment for liver metastases from colorectal cancer (CRC). MATERIALS AND METHODS: Clinical outcomes were evaluated retrospectively among 19 patients with unresectable liver metastases from CRC who had a good performance status and a low burden of extrahepatic disease (EHD) and were eligible for RE. Most (74%) had disease confined to the liver. Concurrent treatment with 5-fluorourail/leucovorin (n = 7) or 5-fluorourail/leucovorin/oxaliplatin (FOLFOX; n = 12) was started 3-4 days before single treatment with RE. RESULTS: Overall response rate according to the Response Evaluation Criteria in Solid Tumors was 84% (two complete responses and 14 partial responses). Median progression-free survival (PFS) time was 10.4 months and median overall survival (OS) time was 29.4 months. For patients with disease confined to the liver, PFS improved (10.7 mo vs 3.6 mo; P = .09), with significant prolongation of OS (median, 37.8 mo vs 13.4 mo; P = .03) compared with those who had EHD. Nine patients, including three long-term (> 3 y) survivors, remained alive after a median follow-up of 18.6 months. Serious treatment-related toxicities included febrile neutropenia with concurrent FOLFOX treatment, a perforated duodenal ulcer, and one death from hepatic toxicity. CONCLUSIONS: The present findings confirm the effectiveness of RE plus systemic chemotherapy for metastatic CRC. Patients with liver-confined disease derived the greatest benefit, with median survival times beyond 36 months. Larger datasets from ongoing phase III trials are needed to further define the safety and efficacy of RE in the first-line setting.

Management of metastatic carcinoma of the uveal tract: an evidence-based analysis.

Uveal metastasis from carcinoma is the most common cause of ocular malignancy in adults and represents an increasing problem in the context of an ageing population and enhanced survival of stage IV cancer patients. The reported prevalence of clinically evident uveal metastases in carcinoma patients ranges from 2% to 9%, with breast and lung cancer together accounting for between 71% and 92% of cases. Most patients (66-97%) have a known history of cancer and, although the majority have metastatic lesions elsewhere, up to 33% may present with an isolated ocular metastasis. These lesions may progress rapidly and are potentially sight-threatening. Early diagnosis and appropriate timely treatment are therefore of paramount importance to maintain patients' quality of life. The diagnosis is usually clinical and detailed descriptions of symptomatology and physical characteristics are provided. In 21-50% of patients, involvement is bilateral. External beam radiotherapy (EBRT), chemotherapy, hormone and biological therapies, brachytherapy, transpupillary thermotherapy, laser photocoagulation/photodynamic therapy and enucleation are therapeutic modalities described in the literature for the management of uveal metastases. The strongest evidence favours timely EBRT for the management of sight-threatening uveal metastases. The published evidence supporting EBRT for sight-threatening uveal metastases was given a grade B (strong support for recommendation). Newer alternative therapies are emerging and may have a role in selected patients; however, there are unfortunately few large studies examining such treatments for carcinoma metastatic to the eye. The role of these modalities will be further clarified with the results of larger comparative trials.

A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer.

PURPOSE: Pemetrexed and vinorelbine are active antineoplastic agents in non-small cell lung cancer (NSCLC). Phase I objectives include maximum tolerated dose (MTD) and recommended phase II dose determination, and pharmacokinetics of the pemetrexed-vinorelbine doublet in locally advanced or metastatic solid tumor patients (pts). Phase II objectives include tumor response evaluation, efficacy, and toxicity for first-line treatment of advanced NSCLC. EXPERIMENTAL DESIGN: Phase I pts received pemetrexed (day 1, 300-700 mg/m2) and vinorelbine (days 1 and 8, 15-30 mg/m2) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B12 supplementation were given. RESULTS: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700 mg/m2 and vinorelbine 30 mg/m2; and recommended phase II dose was pemetrexed 500 mg/m2 and vinorelbine 30 mg/m2. When administered in combination, pemetrexed and vinorelbine pharmacokinetics were consistent with single-agent administration. Thirty-seven (36 chemonaive) phase II NSCLC pts received pemetrexed-vinorelbine. Evaluable tumor response was 40%, with intent-to-treat 38%. One drug-related death occurred from febrile neutropenia with Staphylococcal infection. Grade 3/4 hematologic toxicities were neutropenia (65%) and febrile neutropenia (11%), while prevalent grade 3/4 non-hematologic toxicity was fatigue (27%). CONCLUSION: The pemetrexed-vinorelbine combination is well tolerated and shows activity as first-line treatment in advanced NSCLC patients.