Albumin-based cancer therapeutics for intraperitoneal drug delivery : a review

Albumin is a remarkable carrier protein with multiple cellular receptor and ligand binding sites, which are able to bind and transport numerous endogenous and exogenous compounds. The development of albumin-bound drugs is gaining increased importance in the targeted delivery of cancer therapy. Intraperitoneal (IP) drug delivery represents an attractive strategy for the local treatment of peritoneal metastasis (PM). PM is characterized by the presence of widespread metastatic tumor nodules on the peritoneum, mostly originating from gastro-intestinal or gynaecological cancers. Albumin as a carrier for chemotherapy holds considerable promise for IP delivery in patients with PM. Data from recent (pre)clinical trials suggest that IP albumin-bound chemotherapy may result in superior efficacy in the treatment of PM compared to standard chemotherapy formulations. Here, we review the evidence on albumin-bound chemotherapy with a focus on IP administration and its efficacy in PM

Pegylated liposomal doxorubicin (PLD) in daily practice—A single center experience of treatment with PLD in patients with comorbidities and older patients with metastatic breast cancer

Abstract Purpose Real‐world data about pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC) are limited. We have aimed to highlight the role of PLD in daily practice focusing on older patients and patients with comorbidities with MBC. Methods We analyzed electronic records of all patients with advanced/metastatic breast cancer treated with single‐agent PLD at the University Hospital Basel between 2003 and 2021. Primary endpoint was time to next chemotherapy or death (TTNC). Secondary endpoints were overall survival (OS), progression‐free survival (PFS), and overall response rate (ORR). We performed univariate and multivariate analysis for clinical variables. Results 112 patients with MBC having received single‐agent PLD in any treatment line were analyzed, including 34 patient who were older than 70 years and 61 patients with relevant comorbidities. Median TTNC, OS, and PFS for treatment with PLD were 4.6, 11.9, and 4.4 months, respectively. ORR was 13.6%. Age >70 years predicted shorter OS (median 11.2 months) in multivariate analysis (hazard ratio [HR] 1.83, 95% CI 1.07–3.11, p = 0.026). Age and comorbidities did not significantly affect other endpoints. Unexpectedly, hypertension predicted longer TTNC (8.3 months, p = 0.04) in univariate analysis, maintained in multivariate analysis as a trend for both TTNC (HR 0.62, p = 0.07) and OS (HR 0.63, p = 0.1). Conclusion Age predicted shorter OS significantly but median OS was not relevantly shorter in older patients. PLD remains a treatment option in patients with comorbidities and older patients with MBC. However, our real‐world results of PLD appear underwhelming compared to relevant phase II trials through all age groups, pointing to an efficacy‐effectiveness gap, possibly due to sampling bias

Folate-Targeted Surface-Enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detection of Microscopic Ovarian Cancer

Ovarian cancer has a unique pattern of metastatic spread, in that it initially spreads locally within the peritoneal cavity. This is in contrast to most other cancer types, which metastasize early on <i>via</i> the bloodstream to distant sites. This unique behavior opens up an opportunity for local application of both therapeutic and imaging agents. Upon initial diagnosis, 75% of patients already present with diffuse peritoneal spread involving abdominal organs. Complete resection of all tumor implants has been shown to be a major factor for improved survival. Unfortunately, it is currently not possible for surgeons to visualize microscopic implants, impeding their removal and leading to tumor recurrences and poor outcomes in most patients. Thus, there is a great need for new intraoperative imaging techniques that can overcome this hurdle. We devised a method that employs folate receptor (FR)-targeted surface-enhanced resonance Raman scattering (SERRS) nanoparticles (NPs), as folate receptors are typically overexpressed in ovarian cancer. We report a robust ratiometric imaging approach using anti-FR-SERRS-NPs (αFR-NPs) and nontargeted SERRS-NPs (nt-NPs) multiplexing. We term this method “topically applied surface-enhanced resonance Raman ratiometric spectroscopy” (TAS3RS (“tasers”) for short). TAS3RS successfully enabled the detection of tumor lesions in a murine model of human ovarian adenocarcinoma regardless of their size or localization. Tumors as small as 370 μm were detected, as confirmed by bioluminescence imaging and histological staining. TAS3RS holds promise for intraoperative detection of microscopic residual tumors and could reduce recurrence rates in ovarian cancer and other diseases with peritoneal spread

Supplementary Material for: Total or Subtotal Colectomy in Patients Undergoing Surgery for Primary or Recurrent Epithelial Ovarian Cancer

<b><i>Background: </i></b>There is controversy as to whether performing a total or subtotal colectomy is justified in patients with advanced ovarian cancer, given its potential for morbidity and a negative effect on long-term quality of life. The aim of this study was to assess the perioperative complications, mortality and outcomes of patients who underwent total or subtotal colectomy as part of the surgical procedure for primary or recurrent epithelial ovarian cancer. <b><i>Patients and Methods: </i></b>All patients who had undergone surgery including a total or subtotal colectomy for advanced or recurrent ovarian cancer between 2005 and 2013 at our institution were retrospectively identified. <b><i>Results: </i></b>In this time period, 339 patients underwent surgery for epithelial ovarian cancer, which in 11 (3%) patients included a total or subtotal colectomy. Severe grade 3-4 postoperative complications occurred in 3 (27%) patients, and 1 (9%) patient died within 60 days of surgery. <b><i>Conclusion: </i></b>A total or subtotal colectomy is associated with increased but acceptable morbidity in selected patients undergoing primary cytoreductive surgery. However, in the recurrent/palliative setting, total or subtotal colectomy should be avoided as the prognosis is poor and the morbidity outweighs the clinical benefit