The Pre-Analytical CEN/TS Standard for Microbiome Diagnostics—How Can Research and Development Benefit?

Recently, CEN/TS 17626:2021, the European pre-analytical standard for human specimens intended for microbiome DNA analysis, was published. Although this standard relates to diagnostic procedures for microbiome analysis and is relevant for in vitro diagnostic (IVD) manufacturers and diagnostic laboratories, it also has implications for research and development (R&D). We present here why standards are needed in biomedical research, what pre-analytical standards can accomplish, and which elements of the pre-analytical workflow they cover. The benefits of standardization for the generation of FAIR (findable, accessible, interoperable, reusable) data and to support innovation are briefly discussed.     

A phase I evaluation of the effect of curcumin on dose‐limiting toxicity and pharmacokinetics of irinotecan in participants with solid tumors

Curcumin inhibits UDP‐glucuronyltransferases, a primary metabolic pathway for cancer chemotherapeutic agents like irinotecan. Concurrent administration of both agents may exacerbate irinotecan toxicity. We conducted this phase I study to determine the safety of concurrent curcumin and irinotecan administration. Ten participants with advanced solid tumors received one of four doses (1, 2, 3, and 4 g) of a curcumin phosphatidylcholine complex (PC) orally daily, and 200 mg/m² of i.v. infusion irinotecan on days 1 and 15 of a 28‐day cycle, to determine the maximum tolerated dose (MTD) of PC. Thirteen participants received 4 g of PC (MTD) to assess the effect on the pharmacokinetic (PK) properties of irinotecan and its metabolites, SN‐38 and SN‐38G. Irinotecan, SN‐38, and SN‐38G exposure equivalence with and without curcumin was assessed using area under the plasma concentration‐time curves from 0 to 6 h (AUC_0‐6h). Safety assessments and disease responses were also evaluated. The combination of irinotecan and PC was well‐tolerated. Because there was no dose limiting toxicity, the maximum dose administered (4 g) was defined as the recommended phase II dose of PC. PC did not significantly alter the plasma exposure and other PK properties of irinotecan and its metabolites. There was no apparent increase in the incidence of irinotecan‐associated toxicities. The objective response rate was 3/19 (22%, 95% confidence interval [CI]: 5–39%), median progression free survival and overall survival (n = 23) were 4 months (95% CI: 2.9–8.9 months) and 8.4 months (95% CI: 3.7 – not evaluable [NE]), respectively. Future studies are required to evaluate the efficacy of this combination.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Curcumin can be safely administered with some standard chemotherapy agents like gemcitabine, taxanes, and 5‐fluorouracil.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Both curcumin and irinotecan are metabolized by UGT enzymes and concurrent administration may affect the pharmacokinetics (PKs) and clinical effect of irinotecan. This study sought to assess the effect of curcumin on the PK properties and adverse effect profile of irinotecan.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Up to 4 g of a phosphatidylcholine curcumin (PC) formulation can be safely administered with irinotecan without an impact on the PK and adverse event profile of irinotecan.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Curcumin’s anticancer properties have been documented. Higher doses of PC can be investigated to determine a dose that acts synergistically with irinotecan to improve clinical outcomes.     

Peri-operative outcomes of patients with stage IV endometriosis undergoing robotic-assisted laparoscopic surgery

We analyzed peri-operative outcomes of 80 patients who underwent robotic-assisted laparoscopic surgery and were diagnosed with stage IV endometriosis (revised American Society for Reproductive Medicine) between January 2007 and December 2010 at a tertiary gynecologic oncology referral center with a fellowship training program. Eligible women had a combination of one or more factors: pelvic mass, sub-acute or chronic pelvic pain, dysmenorrhea, dyspareunia, elevated serum CA-125, diagnosed with stage IV endometriosis at surgery with robotic-assisted gynecologic procedures using the da Vinci^? Surgical System. The mean age was 43.7?±?7.0?years, body mass index 27.5?±?7.4?kg/m², and 23 (28.9%) patients had prior endometriosis surgery. Presenting symptoms included: chronic pelvic pain (48.8%), dysmenorrhea (40.3%), and dyspareunia (33.8%). Sixty-nine (86%) patients had pelvic masses (43 unilateral and 26 bilateral). Thirty-seven (46.3%) had elevated CA-125 levels (mean 97.9?±?71.6 U/ml). Forty-eight (60%) underwent robotic-assisted laparoscopic hysterectomy (RALH)/bilateral salpingo-oophorectomy (BSO), 9 (11.3%) RALH/unilateral salpingo-oophorectomy (USO), 5 (6.3%) modified radical hysterectomy, and 10 (13%) USO or BSO only. Four (5%) had ovarian cystectomies with excision of endometriotic implants. Three (3.8%) underwent appendectomy and no patient required bowel resection. Four (5%) patients required conversion to laparotomy during the first 15 cases of this series [dense adhesions (3) and ureteral injury (1)]. Mean operative time was 115?±?46?min, blood loss 88?±?67?ml, and length of stay 1.0?±?0.4?days. There were four (5%) complications (ureteral injury, cuff abscess, cuff hematoma, re-admission for nausea and vomiting secondary to narcotics) and no transfusions. One (1.3%) patient underwent a second surgery for pain (dyspareunia). Robotic-assisted surgery for stage IV endometriosis resulted in excellent pain relief, with few laparotomy conversions or complications during a robotic learning-curve experience.