ABSTRACT
OBJECTIVES: Bendamustine is a unique cytotoxic agent active against various human malignancies, including chronic lymphocytic leukemia (CLL). In vitro studies suggest that cytotoxic activity of bendamustine on CLL-derived cells is synergized by rituximab. A retrospective chart review was conducted to characterize treatment-naïve outpatients and those with relapsed disease aged 70 years and over with CLL receiving bendamustine (with or without rituximab) and to evaluate real-world patterns of care, safety, and effectiveness. METHODS: Using McKesson Specialty Care/US Oncology Network iKnowMed databases, 91 outpatients with at least two recorded visits and at least two cycles of bendamustine monotherapy or bendamustine-rituximab combination therapy were identified and included. Mean age at diagnosis and start of first therapy was 70.3 and 77.4 years respectively, and 63.7% of patients were men. RESULTS: Observed overall response rate was 56.3% in pooled treatment-naïve patients [n = 9; complete response (CR) 18.8%; partial response (PR) 37.5%; nodular partial response (nPR) 0%] and 58.7% in pooled patients with relapsed disease (n = 44; CR 13.3%; PR 44.0%; nPR 1.3%). Median time to progressive disease has not been reached for the 16 treatment-naïve patients (median follow up 15.1 months), and was 18.4 months for those with relapsed disease (n = 73). No unexpected toxicities were observed. Overall rate of blood/bone marrow toxicities (all grades) was 40.7%; grade 3/4 rates were 18.8% in treatment-naïve patients and 25.3% in those with relapsed disease. Most frequent nonhematologic adverse events were fatigue and rash. CONCLUSION: In this retrospective chart review of 91 outpatients with CLL aged 70 years and over, bendamustine (with or without rituximab) was an effective therapeutic option with manageable toxicity.
ABSTRACT
PURPOSE: The study objective was to compare the overall survival (OS) of patients with unresectable or metastatic hepatocellular carcinoma (HCC) treated with nolatrexed (NOL) or doxorubicin (DOX). PATIENTS AND METHODS: Patients from North America, Europe, and South Africa (N = 445) with HCC were randomly assigned to receive NOL or DOX. Eligible patients had Karnofsky performance status (KPS) > or = 60%, Cancer of the Liver Italian Program (CLIP) score < or = 3, and adequate organ function. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rates, and safety. The treatment groups were well-balanced with regards to age, sex, ethnic origin, and underlying liver disease. Randomization was stratified according to KPS and CLIP score. RESULTS: At the time of the final analysis, 377 patients had died. Median OS was 22.3 weeks for NOL and 32.3 weeks for DOX (P = .0068). The hazard ratio was 0.753 in favor of DOX. Objective response rate (complete response [CR] plus partial response [PR]) was 1.4% for NOL and 4.0% for DOX. Median PFS was 12 weeks for NOL and 10 weeks for DOX (P = .7091). Median time to treatment failure was 8.4 weeks for NOL and 9.1 weeks for DOX (P = .0969). Grade 3 and 4 stomatitis, vomiting, diarrhea, and thrombocytopenia were more common in the NOL arm. Alopecia was more common in the DOX arm. More patients were withdrawn from study for toxicity in the NOL arm than in the DOX arm. CONCLUSION: NOL showed minimal activity in this phase III trial. Further exploration at this dose and schedule in HCC is not warranted.
