First-line use of EGFRI in metastatic colorectal cancer is not cost effective at its current pricing relative to Bev.
BackgroundVCN-01 is an oncolytic adenovirus (Ad5 based) designed to replicate in cancer cells with dysfunctional RB1 pathway, express hyaluronidase to enhance virus intratumoral spread and facilitate chemotherapy and immune cells extravasation into the tumor. This phase I clinical trial was aimed to find the maximum tolerated dose/recommended phase II dose (RP2D) and dose-limiting toxicity (DLT) of the intravenous delivery of the replication-competent VCN-01 adenovirus in patients with advanced cancer.MethodsPart I: patients with advanced refractory solid tumors received one single dose of VCN-01. Parts II and III: patients with pancreatic adenocarcinoma received VCN-01 (only in cycle 1) and nab-paclitaxel plus gemcitabine (VCN-concurrent on day 1 in Part II, and 7 days before chemotherapy in Part III). Patients were required to have anti-Ad5 neutralizing antibody (NAbs) titers lower than 1/350 dilution. Pharmacokinetic and pharmacodynamic analyses were performed.Results26% of the patients initially screened were excluded based on high NAbs levels. Sixteen and 12 patients were enrolled in Part I and II, respectively: RP2D were 1×1013 viral particles (vp)/patient (Part I), and 3.3×1012 vp/patient (Part II). Fourteen patients were included in Part III: there were no DLTs and the RP2D was 1×1013 vp/patient. Observed DLTs were grade 4 aspartate aminotransferase increase in one patient (Part I, 1×1013 vp), grade 4 febrile neutropenia in one patient and grade 5 thrombocytopenia plus enterocolitis in another patient (Part II, 1×1013 vp). In patients with pancreatic adenocarcinoma overall response rate were 50% (Part II) and 50% (Part III). VCN-01 viral genomes were detected in tumor tissue in five out of six biopsies (day 8). A second viral plasmatic peak and increased hyaluronidase serum levels suggested replication after intravenous injection in all patients. Increased levels of immune biomarkers (interferon-γ, soluble lymphocyte activation gene-3, interleukin (IL)-6, IL-10) were found after VCN-01 administration.ConclusionsTreatment with VCN-01 is feasible and has an acceptable safety. Encouraging biological and clinical activity was observed when administered in combination with nab-paclitaxel plus gemcitabine to patients with pancreatic adenocarcinoma.Trial registration numberNCT02045602.
A previously healthy 42 year-old woman presented at her family doctor after her hairdresser noticed a nodule in the left temporo-parietal area of the scalp. The mass was a firm, reddish nodule measuring approximately 3 × 2 cm. The patient was completely asymptomatic. She was referred to dermatology, and the lesion was excised. The initial pathology report showed a moderately-well differentiated adenocarcinoma. It was unclear at this time whether this was a primary lesion of the sweat gland or metastatic adenocarcinoma from another site. She was then referred to our centre for oncologic work-up.The pathology was reviewed and confirmed a moderately differentiated adenocarcinoma (Figure 1). The tumour was formed by single tubules or complex back to back tubular structures with areas where the luminal cells showed apical snouts. The lesion filled the reticular dermis without involving the epidermis. No perineural or lymphovascular invasion was present. The resection margins were clear, with the closest margin at 2 mm. The immunohistochemistry showed positivity for CK 7, ER, PR, Androgen receptor, CDX2, Ber ep4 and EMA. It was found to be negative for High molecular weight keratin, CK 20, COX2, CDX2, TTF1, Renal cell marker, CD 117, and CEA. It was concluded that this profile was most consistent with a metastatic breast carcinoma; however an eccrine/apocrine carcinoma of the skin could not be completely ruled out.On physical examination, there was no palpable lymphadenopathy of the neck, supraclavicular or infraclavicular regions bilaterally. No pre-or postauricular lymphadenopathy. On the left temporal parietal scalp, there was a 3 cm, well-healed scar, with no signs of infection or IntroductionPrimary cutaneous apocrine carcinoma (PCAC) is a rare type of sweat gland neoplasm with incidence rates estimated to range from 0.0049-0.0173 per 100,000 patients per year [1]. Approximately 200 total cases are reported in the literature. PCAC occurs in areas with large numbers of apocrine glands [2]. The scalp is among one of the rarest sites of occurrence, while the axilla appears most commonly [3]. Among the 186 cases reviewed by Hollowell, equal distribution was present in both males and females, with 76% of the sample population of Caucasian ethnicity. Median age was calculated at 67 years for this sample, which is the largest cohort studied to date [1].PCAC can develop in the dermal and subcutaneous layers of the skin, occasionally infiltrating the epidermal layer resulting in ulceration. PCAC has a diverse presentation, occurring as both uniand multi-nodular growths with varying colour [2]. Often these neoplasms are indurated, painless masses and can be associated with benign lesions [2], including a nevus sebaceous, most commonly seen with scalp lesions [4][5][6]. Development of these lesions typically occurs within a year before diagnosis [7]; however several cases have reported longer durations with a period of rapid growth [4,5,8,9]. PCAC is often quite difficult to differentiate from metastases of adenocarcinoma o...
Neuroendocrine neoplasms (NENs) comprise a broad spectrum of tumors with widely variable biological and clinical behavior. Primary tumor site, extent of disease, tumor differentiation and expression of so matostatin receptors, proliferation and growth rates are the major prognostic factors that determine the therapeutic strategy. Treatment options for advanced disease have considerably expanded in recent years, particularly for well differentiated tumors (NETs). Novel drugs approved over the past decade in this context include somatostatin analogues and 177Lu-oxodotreotide for somatostatin-receptor-positive gastroenteropancreatic (GEP) NETs, sunitinib for pancreatic NETs (P-NETs), and everolimus for P-NETs and non-functioning lung or gastrointestinal NETs. Nevertheless, chemotherapy remains an essential component of the treatment armamentarium of patients with NENs, particularly of patients with P-NETs or those with bulky, symptomatic or rapidly progressive tumors (generally G3 or high-G2 NENs). In this manuscript we will comprehensively review available evidence related to the use of chemotherapy in lung and GEP NENs and will critically discuss its role in the treatment algorithm of this family of neoplasms.
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