Francesca Aroldi

Pancreatic cancer: New hopes after first line treatment.

Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Extensive research has yielded advances in first-line treatment strategies, but there is no standardized second-line therapy. In this review, we examine the literature trying to establish a possible therapeutic algorithm.

Tyrosine Kinase Inhibitors in EGFR-Mutated Large-Cell Neuroendocrine Carcinoma of the Lung? A Case Report.

Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a high-grade carcinoma belonging to the neuroendocrine tumors of the lung and is different from typical lung large-cell carcinoma. It represents about 3% of all pulmonary malignancies and is characterized by neuroendocrine cytologic features. The treatment usually is platinum-based chemotherapy, however the outcome remains poor. Therefore new therapeutic options are needed. Tyrosine kinase inhibitors have demonstrated greater efficacy and better tolerability than standard chemotherapy in non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations. EGFR gene mutations were also rarely identified in LCNEC. We report a patient with lung LCNEC activating EGFR mutations who showed an impressive response to gefitinib.

Chemotherapy rechallenge after regorafenib treatment in metastatic colorectal cancer: still hope after the last hope?

Introduction: The introduction of biological agents in cancer therapy is changing the progression of metastatic colorectal cancer. Currently, resistance to biological agents is an emerging problem; the progression of the disease is caused by the development of resistant clones. According to some authors, these clones can be re-sensitized to traditional and previously utilized chemotherapy agents. The results of the CORRECT study demonstrated the efficacy of regorafenib monotherapy in both KRAS wild type and mutant pretreated patients (pts). Two recent reports showed the potential of reintroduction of chemotherapy, even after treatment with regorafenib. Patients and methods: We performed a retrospective review of clinical data from patients treated with regorafenib at our institution between March 2012 and March 2013. We analysed patient characteristics, KRAS/NRAS status, response to treatment (evaluated by RECIST v1.1 criteria) and survival. Results: Regorafenib was administered to 128 patients, and 11 (8.6%) received post-regorafenib therapy (to our knowledge). Seven (63.6%) patients were wild type for KRAS/NRAS. Post-regorafenib therapy represented for all the patients at least the fourth line: all the pts received both oxaliplatin- and irinotecan-based chemotherapy, all of them were treated with bevacizumab, and 7 patients also received cetuximab. Eight patients (72.7%) were treated with standard chemotherapy after regorafenib (irinotecan monotherapy, capecitabine plus oxaliplatin or irinotecan, dacarbazine or raltitrexed), while 3 patients received an experimental therapy (clinical trial). Nine of the 11 (81.8%) patients had PD and 2 patients had SD. The median progression-free survival was 1.6+ months (range 0.5–3.5), the median OS post-regorafenib was 2.1+ months (range 0.5–10.2) and the 6-month OS was 27.3%. Conclusion: Our retrospective analysis showed that after regorafenib therapy, re-introduction of chemotherapy is possible. Unfortunately, we reported a high percentage of disease progression beyond regorafenib, which is likely due to the high percentage of heavily pretreated patients (some received four or five types of therapy before regorafenib). We think that regorafenib could represent a chemotherapy resensitizing agent; however, additional studies are needed in patients who have received less pretreatment.

Immunotherapy for pancreatic cancer: present and future

Despite the identification of some efficient drugs for the treatment of metastatic pancreatic cancer, this tumor remains one of the most lethal cancers and is characterized by a strong resistance to therapies. Pancreatic cancer has some unique features including the presence of a microenvironment filled with immunosuppressive mediators and a dense stroma, which is both a physical barrier to drug penetration and a dynamic entity involved in immune system control. Therefore, the immune system has been hypothesized to play an important role in pancreatic cancer. Thus, therapies acting on innate or adaptive immunity are being investigated. Here, we review the literature, report the most interesting results and hypothesize future treatment directions.

Oxaliplatin-induced hypersensitivity reaction: underlying mechanisms and management

Abstract Hypersensitivity reactions are rare but feared drugs adverse effect. These reactions are not uncommon with anticancer drugs, such as taxanes, monoclonal antibodies, and platinum compounds. Oxaliplatinum, a third-generation platinum compound, one of the mainstay drugs in the treatment of many gastrointestinal cancers, can give rise to hypersensitivity reactions, sometimes with fatal outcomes. In this paper, we reviewed the incidence and mechanisms underlying the occurrence of this event, highlighting the most recent advances concerning the pathogenesis of the reaction and also reporting possible risk factors identified and the most effective treatment in preventing the onset of this event.

Assessing cancer caregivers' needs for an early targeted psychosocial support project: The experience of the oncology department of the Poliambulanza Foundation.

OBJECTIVE Caregivers play a key role in the management of patients with cancer. However, some studies have suggested that caregivers have even more unmet needs than the patients. METHOD To better identify the needs and changes in the lifestyles of the caregivers in our practice and to plan a targeted support project to decrease caregiver burden, we administered the Caregivers QoL Index-Cancer (CQoLC) to 200 consecutive caregivers. This questionnaire assesses psychological well-being, the relationship with healthcare professionals, administration of finances, lifestyle disruption, and positive adaptation. RESULTS Our data showed that being a caregiver to a patient with metastatic disease negatively affected females mostly with regard to mental and emotional burden, while men complained more about their sexual life (42.3 vs. 33.6%), although this result was not significant. Some 93.5% of caregivers reported that they were pleased with their role, while 83.4% were concerned about financial difficulties. SIGNIFICANCE OF RESULTS We strongly believe that early supportive care directed not only at patients but also to caregivers may improve the quality of life (QoL) in this population. We are currently developing a targeted support project to decrease caregiver burden.

Blind Snipers: Relevant Off Target Effects of Non-chemotherapeutic Agents in Oncology: Review of the Literature.

In recent years an increasing attention is focused on the potential effects of drugs on cancer incidence and/or cancer survival. Many medications of common use, developed for a variety of medical non-cancer situations, have been found to have potential anti- cancer effects. In this article, we performed an overview of the literature evidence for several commonly used non-cancer medications, such as aspirin, beta-blockers, metformin and other anti- diabetics, cardiac glycosides, anticoagulant heparin, statins, psychotropic drugs, vitamins, calcium and estrogens which have been shown to have anticancer effects, in observational and experimental studies. A huge amount of data supports the idea that a few of these commonly used medicines could decrease cancer death-rate, particularly aspirin, statins and metformin, crosswise different types of cancer. To date, no mature data are available from randomized and prospective trials; perhaps, the results of some studies underway will allow us to answer some questions on the possible use of these drugs in our clinical practice in primary and secondary prevention, or even in adjuvant setting.

GEMOX: An Active Regimen for the Treatment of Luminal and Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer

Background: Pretreated metastatic breast cancer (MBC) remains a formidable challenge with unmet needs both in terms of prolonged survival and quality-of-life-related issues. Methods: We collected data from 27 MBC patients treated with gemcitabine and oxaliplatin (GEMOX) at our institution between June 2009 and April 2015. The patients were heavily pretreated, and all had previously been exposed to anthracyclines and taxanes. Results: We achieved a complete response in 1 patient (4%), a partial response in 7 patients (26%) and stable disease in 12 patients (44%), while 6 patients (22%) experienced progressive disease. The response of 1 patient (4%) could not be evaluated because she interrupted her treatment during the first cycle due to a major reaction to oxaliplatin. We observed grade 4 hypertransaminasaemia in only 1 patient (4%) and grade 2 neuropathy in 16 patients (59%). Grade 3 leuconeutropenia was observed in 5 patients (18%). The median progression-free survival was 5.9 months and the median overall survival was 9.6 months. Conclusions: GEMOX is an efficient and well-tolerated salvage regimen for MBC patients.

Current Role of Minimally Invasive Radical Cholecystectomy for Gallbladder Cancer

Background. For Tis and T1a gallbladder cancer (GbC), laparoscopic cholecystectomy can provide similar survival outcomes compared to open cholecystectomy. However, for patients affected by resectable T1b or more advanced GbC, open approach radical cholecystectomy (RC), consisting in gallbladder liver bed resection or segment 4b-5 bisegmentectomy, with locoregional lymphadenectomy, is considered the gold standard while minimally invasive RC (MiRC) is skeptically considered. Aim. To analyze current literature on perioperative and oncologic outcomes of MiRC for patients affected by GbC. Methods. A Medline review of published articles until June 2016 concerning MiRC for GbC was performed. Results. Data relevant for this review were presented in 13 articles, including 152 patients undergoing an attempt of MiRC for GbC. No randomized clinical trial was found. The approach was laparoscopic in 147 patients and robotic in five. Conversion was required in 15 (10%) patients. Postoperative complications rate was 10% with no mortality. Long-term survival outcomes were reported by 11 studies, two of them showing similar oncologic results when comparing MiRC with matched open RC. Conclusions. Although randomized clinical trials are still lacking and only descriptive studies reporting on limited number of patients are available, current literature seems suggesting that when performed at highly specialized centers, MiRC for GbC is safe and feasible and has oncologic outcomes comparable to open RC.

QT Prolongation and Anticancer Drugs: Is it a Cardiologist’s Worry? The Oncologist’s Point of View

Currently, many novel therapies are available for physicians treating cancer; some of them are associated with adverse cardiac events. One of the most worrisome cardiac event is QT prolongation, which is a risk factor for developing the potentially fatal torsade de pointe. Many classes of drugs, both anticancer and concomitant agents, are involved in this issue. We report a review of old and new commonly used agents with torsadogenic potential.