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Del Pup L.,Italian National Cancer Institute | Di Francia R.,Hematology Oncology and Stem Cell Transplantation Unit | Cavaliere C.,Istituto Nazionale per Lo Studio e la Cura Dei Tumori Fondazione Giovanni Pascale | Facchini G.,Istituto Nazionale per Lo Studio e la Cura Dei Tumori Fondazione Giovanni Pascale | And 3 more authors.
Anti-Cancer Drugs

Urogenital symptoms resulting from estrogen deficiency are common problems that impair quality of life and sexuality. Potentially, one out of three postmenopausal women could benefit from a vaginal estrogen therapy, but the fear of systemic absorption limits its use. Promestriene used vaginally to relieve vaginal atrophy is a locally effective estrogen that has not shown systemic estrogenic effects. Thus, it could be a first-line option for those who necessitate a minimal or ideally no vaginal absorption, particularly in symptomatic cancer patients. There are little data available in the literature, mostly consisting of small, open-label, short duration studies, and few randomized-controlled studies. After a long-term market experience (almost 40 years), in 34 countries, and millions of pieces prescribed, the side effects were very rarely reported in pharmacovigilance data, whereas the effectiveness to relieve atrophy was good. To further improve promestriene safety, especially in estrogen-sensitive cancer patients, a very low dose is used from the beginning, starting from half or less of the usual dose, and then gradually increased till the minimum effective dose, which could further reduce its already minimal vaginal absorption. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Del Pup L.,Italian National Cancer Institute | Mantovani A.,National Institute of Health | Luce A.,The Second University of Naples | Di Francia R.,Hematology Oncology and Stem Cell Transplantation Unit | And 2 more authors.
Oncology Reports

Pollutants altering the endocrine system, known as endocrine disruptors (ED), may modify the risk of female cancers. The carcinogenic effect of ED on humans has been confirmed by experimental studies for various substances including pesticides, DDT, dioxins, phthalates, bisphenol A, diethylstilbestrol, as well as heavy metals, but it is difficult to quantify precisely for several reasons hereby reviewed. Carcinogenesis is a complex and multifactorial mechanism that manifests itself over a long period of time, making difficult the detection of the specific contribution of the pollutants, whose absorbed dose is often unknown. The combined effect of various substances leads to complex interactions whose outcome is difficult to predict. These substances may accumulate and carry out their harmful effect on critical periods of life, probably also at doses considered harmless to an adult. ED can also have epigenetic adverse effects on the health of future generations. In conclusion, the carcinogenic effects of endocrine disruptors on female cancer types is plausible although additional studies are needed to clarify their mechanisms and entities. In the last part of the review we suggest ways to reduce ED exposure as it is mandatory to implement necessary measures to limit exposure, particularly during those periods of life most vulnerable to the impact of oncogenic environmental causes, such as the embryonic period and puberty. © 2014, Spandidos Publications. All rights reserved. Source

Pinto A.,Hematology Oncology and Stem Cell Transplantation Unit | Corradini P.,Fondazione IRCCS | Corradini P.,University of Milan | Mussetti A.,Fondazione IRCCS | And 2 more authors.
Leukemia and Lymphoma

Standard treatment for patients with Hodgkin lymphoma (HL) unresponsive to upfront therapy or relapsing after primary treatment (RR-HL) consists of salvage chemotherapy followed by autologous stem cell transplant (ASCT). ASCT outcomes are essentially related to two factors: disease burden at the time of transplant and comorbidity status of the patient. Positron emission tomography (PET) scan is a very sensitive diagnostic instrument to measure disease status. In fact, a negative PET status before ASCT is a well-known positive prognostic factor in patients with RR-HL. The recent introduction of the biologically targeted agent brentuximab vedotin has allowed us to treat RR-HL more efficaciously with less toxicity for the patient. Use of this new agent could help achieve a PET-negative status before ASCT in a larger percentage of patients, without severe toxicities, thereby improving ASCT outcomes. Herein we discuss the current evolving scenario of RR-HL treatment. © 2014 Informa UK, Ltd. Source

Zinzani P.L.,University of Bologna | Pellegrini C.,University of Bologna | Cantonetti M.,University of Rome Tor Vergata | Re A.,Spedali Civili | And 7 more authors.

Background. Hodgkin lymphoma (HL) is characterized by the presence of CD30-positive Hodgkin Reed-Sternberg cells. Approximately30%- 40%ofpatientswithadvanceddisease arerefractory to frontline therapy or will relapse after first-line treatment. The standard management of these patients is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant(ASCT).Thebestprognostic factor isthestatusofdisease before ASCT; in particular, the normalization of positron emission tomography (PET) scan. Brentuximab vedotin (BV) has shown a high overall response rate in refractory/relapsed HL after ASCT, whereas few data are available regarding its role before ASCT. Patients and Methods. A multicenter, retrospective, observational study was conducted.The primary endpoint of the study was the effectiveness of BV as single agent in patients with relapsed/refractory, ASCT-naïve HL, determined by the conversion of PET status from positive to negative; secondary endpoints were safety, capacity to proceed to ASCT, survival, and progression-free status. Results. Thirty patients with relapsed/refractory HL- and PETpositive disease after conventional chemotherapy salvage treatments were treated with a median of 4 cycles of BV. Normalization of PET findings (Deauville score#2) occurred in 9 of 30 patients (30%).Those nine patients proceeded to ASCT. Conclusion. These data suggest that BV can normalize PETstatus in a subset of HL patients refractory to conventional chemotherapy salvage treatments, such as ifosfamide-containing regimens, cytarabine- and platinum-containing regimens, prior to ASCT © AlphaMed Press 2015. Source

Golay J.,Ospedale Papa Giovanni XXIII | Semenzato G.,University of Padua | Rambaldi A.,Ospedale Papa Giovanni XXIII | Foa R.,University of Rome La Sapienza | And 7 more authors.

The anti-CD20 antibody rituximab (RTX; Rituxan®, MabThera®) was the first anti-cancer antibody approved by the US Food and Drug Administration in 1997 and it is now the most-studied unconjugated therapeutic antibody. The knowledge gained over the past 15 y on the pharmacodynamics (PD) of this antibody has led to the development of a new generation of anti-CD20 antibodies with enhanced efficacy in vitro. Studies on the pharmacokinetics (PK) properties and the effect of factors such as tumor load and localization, antibody concentration in the circulation and gender on both PK and clinical response has allowed the design of optimized schedules and novel routes of RTX administration. Although clinical results using newer anti-CD20 antibodies, such as ofatumumab and obinutuzumab, and novel administration schedules for RTX are still being evaluated, the knowledge gained so far on RTX PK and PD should also be relevant for other unconjugated monoclonal antibody therapeutics, and will be critically reviewed here. © 2013 Landes Bioscience. Source

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