Stefano Panni

New developments in the treatment of chemotherapy-induced neutropenia: focus on balugrastim

Neutropenia and febrile neutropenia are two major complications of chemotherapy. Dose reductions, delays in treatment administration, and the use of granulocyte colony-stimulating factors are equally recommended options to preserve absolute neutrophil count in case of chemotherapy regimens bringing a risk of febrile neutropenia of 20% or higher. Recombinant granulocyte colony-stimulating factors, such as filgrastim and lenograstim, have a short elimination half-life (t1/2) and need to be used daily, while others, like pegfilgrastim and lipegfilgrastim, are characterized by a long t1/2 requiring only a single administration per cycle. Balugrastim is a novel long-acting recombinant granulocyte colony-stimulating factor obtained by means of a genetic fusion between recombinant human serum albumin and granulocyte colony-stimulating factor. Albumin binding increases the molecular weight and determines a high plasmatic stability leading to a t1/2 of ~19 days. Balugrastim’s efficacy, safety, and tolerability have been assessed in four different clinical trials involving breast cancer patients treated with doxorubicin and docetaxel. Pegfilgrastim was chosen as a comparator. Balugrastim was noninferior to pegfilgrastim with regard to the reduction of mean duration of severe neutropenia during cycle 1. Moreover, both treatments were comparable in terms of efficacy and safety profile. Balugrastim was well tolerated, with the only related adverse event being mild to moderate bone pain. The aim of this review is to summarize the currently available literature data on balugrastim.

Diagnostic use of contrast medium and the kidney: A challenge or a ghost?

The global growing number of contrast-enhanced procedures highlights the risk of contrast media–induced renal damage. This review is an effort to define contrast-induced nephropathy and its pathogenesis, weigh its principal risk factors, give some clarifications about kidney function evaluation tools, acquire some clinical relevance prognostic concerns, and bring into focus preventive measures, with special regard to cancer patients. Our final purpose is focused on the request of diagnostic safety in high-risk patients, which may be achieved without unfair differences in this subgroup, too. A second reading of the scientific evidence may offer a chance to tear down the kidney damage ghost, replacing it with the consciousness of a still existing challenge that engages more than one specialty.

Real-life clinical practice results with vinflunine in patients with relapsed platinum-treated metastatic urothelial carcinoma: an Italian multicenter study (MOVIE-GOIRC 01–2014)

BackgroundVinflunine is the only chemotherapeutic agent shown to improve survival in platinum-refractory patients with metastatic transitional cell carcinoma of the urothelium (TCCU) in a phase III clinical trial, which led to product registration for this indication in Europe. The aim of this study was to assess the efficacy of vinflunine and to evaluate the prognostic significance of risk factors in a large, unselected cohort of patients with metastatic TCCU treated according to routine clinical practice.MethodsThis was a retrospective multicenter study. Italian cancer centers were selected if, according to the Registry of the Italian Medicines Agency (AIFA), at least four patients had been treated with vinflunine between February 2011 and June 2014, after first- or second-line platinum-based chemotherapy. The primary objective was to test whether the efficacy measured by overall survival (OS) in the registration study could be confirmed in routine clinical practice. Multivariate analysis was carried out using Cox proportional hazard model.ResultsA total of 217 patients were treated in 28 Italian centers. Median age was 69 years (IQR 62–76) and 84% were male; Eastern Cooperative Oncology Group performance status (ECOG PS) was ≥ 1 in 53% of patients. The median number of cycles was 4 (IQR 2–6); 29%, 35%, and 36% received an initial dose of 320 mg/m2, 280 mg/m2 or a lower dose, respectively. Median progression-free survival (PFS) and OS for the entire population was 3.2 months (2.6–3.7) and 8.1 months (6.3–8.9). A complete response was observed in six patients, partial response in 21, stable disease in 60, progressive disease in 108, with a disease control rate of 40%. Multivariate analysis showed that ECOG PS, number of metastatic sites and liver involvement were unfavorable prognostic factors for OS. Toxicity was mild, and grade 3–4 adverse effects were mainly: neutropenia (9%), anemia (6%), asthenia/fatigue (7%) and constipation (5%).ConclusionsIn routine clinical practice the results obtained with VFL seem to be better than the results of the registration trial and reinforce evidence supporting its use after failure of a platinum-based chemotherapy.

Modified dose-dense taxotere cisplatin fluorouracil regimen (mTCF-dd) in a large cohort of patients (pts) with metastatic or locally advanced non-squamous gastroesophageal cancer (GEC).

e15552Background: TCF is one of the most effective first-line option in metastatic GEC. We previously reported on the promising and high activity of mTCF-dd (Tomasello G et al: Gastric Cancer 2014 ...

Optimizing chemotherapy in patients with metastatic transitional-cell carcinoma: High rate of complete response with two sequential dose-dense regimens of cisplatin, gemcitabine, paclitaxel, followed by MVAC.

303 Background: Currently, cisplatin, gemcitabine, paclitaxel (CGP) and MVAC are the most active regimens in transitional-cell carcinoma (TCC). We tested the hypothesis that two sequential non-cross-resistant, dose-dense (DD) regimens may target different cancer cells, avoid drug resistance, and improve response rate. Methods: This is a phase II, single institutional trial, including patients (pts) with bladder, renal pelvis, or ureteral TCC. Primary end point was the rate of complete response (CR) after two sequential DD regimens. Primary analysis was carried out in the intention to treat (ITT) population.Patients with histological diagnosis of TCC, PS 0–2 (ECOG), adequate organ function and no previous systemic regimens were treated with 4 cycles of CGP DD followed by 4 cycles of M-VAC DD. All received peg-filgrastim after chemotherapy. Pts were evaluated with CT scan at the baseline, after 4 cycles, at the end of chemotherapy and then every 3 months for 2 years and 6 months thereafter. Results: 44 cons...