Search

Purpose: To compare conventional fractionation radiation therapy (RT), Arm A, vs. split-course accelerated hyperfractionated RT (S-AHF), Arm B, vs. conventional fractionation RT plus concomitant chemotherapy (CT), Arm C, in terms of survival and toxicity for advanced, unresectable epidermoid tumors of oropharynx.Methods and Materials: Between January 1993 and June 1998, 192 previously untreated patients affected with Stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were accrued in a multicenter, randomized Phase III trial (ORO 93-01). For Arms A and C, 66–70 Gy in 33–35 fractions, 5 days a week, were administered in 6.5–7 weeks to tumor and positive nodes. In Arm B, the dose delivered to tumor and involved nodes was 64–67.2 Gy, giving 2 fractions of 1.6 Gy every day with an interfraction interval of at least 4 h and preferably 6 h, 5 days a week. At 38.4 Gy, a 2-week split was planned; after the split, RT was resumed with the same modality. In Arm C, CT regimen consisted of carboplatin and 5-fluorouracil (CBDCA 75 mg/m2, Days 1–4; 5-FU 1,000 mg/m2 i.v. over 96 h, Days 1–4, recycling every 28 days (at 1st, 5th, and 9th week).Results: No statistically significant difference was detected in overall survival (p = 0.129): 40% Arm A vs. 37% Arm B vs. 51% Arm C were alive at 24 months. Similarly, there was no statistically significant difference in terms of event-free survival (p = 0.196): 20% for Arm A, 19% for Arm B, and 37% for Arm C were event free at 24 months. On the contrary, the 2-year disease-free survival was significantly different among the three arms (p = 0.022), with a superiority for Arm C. At 24 months, the proportion of patients without relapse was 42% for Arm C vs. 23% for Arm A and 20% for Arm B. Patients in Arm A less frequently developed G3+ acute mucositis than their counterparts in Arm B or C (14.7% vs. 40.3% vs. 44%). Regarding the CT-related acute toxicity, apart from 1 case of fatal nephrotoxicity, only hematologic G3+ (Grade 3 or higher) acute sequelae were observed (World Health Organization scale), most commonly leukopenia (22.7%). Arm C showed slightly more G3+ skin, s.c. tissue, and mucosal late side effects (RTOG scale), although significant sequelae were relatively uncommon, and mucosal sequelae were most commonly transient. The occurrence of persistent G3 xerostomia was comparable in all three treatment arms.Conclusions: The combination of simultaneous CT and RT with the regimen of this trial is better than RT alone in advanced oropharyngeal squamous-cell carcinomas, by increasing disease-free survival. This improvement, however, did not translate into an overall survival improvement, and was associated with a higher incidence of acute morbidity. [Copyright &y& Elsevier]

Selective phosphodiesterase 5 inhibitors, including sildenafil, tadalafil and vardenafil, are widely-used in the treatment of erectile dysfunction and pulmonary arterial hypertension. They are also well-known as examples of successful drug repurposing in that they were initially developed for angina and only later developed for erectile dysfunction. However, these drugs may also be effective cancer treatments. A range of evidentiary sources are assessed in this paper and the case made that there is pre-clinical and clinical evidence that these drugs may offer clinical benefit in a range of cancers. In particular, evidence is presented that these drugs have potent immunomodulatory activity that warrants clinical study in combination with check-point inhibition. [ABSTRACT FROM AUTHOR]

Among the various measures proposed to combat the challenge of financial toxicity in cancer care, an important strategy is the use of lower-priced drugs instead of expensive alternatives. However, the oncology community seems to either ignore or more readily reject cheaper drugs in cancer care compared to more expensive alternatives. In this commentary, we present three examples of lower-priced drugs rejected or ignored by the oncology community and contrast this with three expensive drugs where persistent optimism remained despite negative clinical trial results. We argue that all drugs be held to the same rigorous standards - this not only includes skepticism in the absence of sound evidence, but also the suspension of premature judgement as has happened in the cases of repurposed drugs. [ABSTRACT FROM AUTHOR]

In cancer survivors, chemotherapy-associated adverse neurological effects are described as side effects in non-targeted tissue. We investigated the role of redox-imbalance in neuronal damage by a relative low dose of Docetaxel (DTX). The neuroblastoma cells (SH-SY5Y cells) were exposed to DTX at a dose of 1.25 nM for 6 h. Antioxidant defenses (i.e. ascorbic acid, glutathione, and catalase) and lipid oxidation products (i.e. F2-isoprostanes) were evaluated. To investigate cell ultrastructure and tubulin localisation, transmission electron microscopy (TEM) and immunofluorescence techniques were applied. In the SH-SY5Y cells, DTX induced a significant reduction of total glutathione (P < 0.001) and ascorbic acid (P < 0.05), and an increase in both total F2-Isoprostanes (P < 0.05) and catalase activity (P < 0.05), as compared to untreated cells. Additionally, TEM showed a significant increase in cells with apoptotic characteristics. Immunolocalisation of tubulin showed a compromised cytoskeletal organisation. The investigated sublethal dose of DTX, to which non-targeted cells may be exposed throughout the duration of chemotherapy treatment, induces a redox imbalance resulting in a specific modulation of the antioxidant response. This study provides new insights into DTX-induced cellular mechanisms useful for evaluating whether the concomitant use of antioxidants associated with chemotherapy mitigates chemotherapy side effects in cancer survivors. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most frequent cancer among women in the world and it remains a leading cause of cancer death in women globally. Among BCs, triple negative breast cancer (TNBC) is the most aggressive, and for its histochemical and molecular characteristics is also the one whose therapeutic opportunities are most limited. The REpurposing Drugs in Oncology (ReDO) project investigates the potential use of off patent non-cancer drugs as sources of new cancer therapies. Repurposing of old non-cancer drugs, clinically approved, off patent and with known targets into oncological indications, offers potentially cheaper effective and safe drugs. In line with this project, this article describes a comprehensive overview of preclinical or clinical evidence of drugs included in the ReDO database and/or PubMed for repurposing as anticancer drugs into TNBC therapeutic treatments. [ABSTRACT FROM AUTHOR]

Repurposing is a drug development strategy that seeks to use existing medications for new indications. In oncology, there is an increased level of activity looking at the use of non-cancer drugs as possible cancer treatments. The Repurposing Drugs in Oncology (ReDO) project has used a literature-based approach to identify licensed non-cancer drugs with published evidence of anticancer activity. Data from 268 drugs have been included in a database (ReDO_DB) developed by the ReDO project. Summary results are outlined and an assessment of clinical trial activity also described. The database has been made available as an online open-access resource (http://www.redo-project. org/db/). [ABSTRACT FROM AUTHOR]

Purpose Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. Materials and Methods A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibs were subjected to a novel integrative "omic" approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-step whole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients' peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants. Results Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none of which, except one, shared with the healthy sib, pinpointing to a "private" oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR. Conclusion In the era of precision medicine, this report emphasizes the importance of an "omic" approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well. [ABSTRACT FROM AUTHOR]

Only one case of lymphoepithelioma-like carcinoma of the ovary has been reported so far. A new case is herein illustrated in a 69-year-old woman: an ovarian mass adherent to urinary bladder dome with peritoneal carcinomatosis. Histologically, undifferentiated carcinomatous areas were intermingled with abundant lymphoid tissue. Epstein-Barr virus has not been detected either in neoplastic or in lymphoid cells. [ABSTRACT FROM PUBLISHER]