Phenotype-guided targeted therapy based on functional signal transduction pathway activity in recurrent ovarian cancer patients: The STAPOVER study protocol.

Objective: Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors. Quantitative assessment of functional signal transduction pathway (STP) activity from mRNA measurements of target genes is an alternative approach. Therefore, we aim to identify aberrantly activated STPs in tumour tissue of patients with recurrent ovarian cancer and start phenotype-guided targeted therapy to improve survival without compromising quality of life. Study design: Patients with recurrent ovarian cancer and either 1) have platinum-resistant disease, 2) refrain from standard therapy or 3) are asymptomatic and not yet eligible for standard therapy will be included in this multi-centre prospective cohort study with multiple stepwise executed treatment arms. Targeted therapy will be available for patients with aberrantly high functional activity of the oestrogen receptor, androgen receptor, phosphoinositide 3-kinase or Hedgehog STP. The primary endpoint of this study is the progression-free survival (PFS) ratio (PFS2/PFS1 ratio) according to RECIST 1.1 determined by the PFS on matched targeted therapy (PFS2) compared to PFS on prior therapy (PFS1). Secondary endpoints include among others best overall response, overall survival, side effects, health-related quality of life and cost-effectiveness. Conclusion: The results of this study will show the clinical applicability of STP activity in selecting recurrent ovarian cancer patients for effective therapies.

UGT1A1 genotype-guided dosing of irinotecan: time to prioritize patient safety.

Tweetable abstract Pretreatment UGT1A1 genotyping and a 70% irinotecan dose intensity in poor metabolizers is safe, feasible, cost-effective and essential for safe irinotecan treatment in cancer patients. It is time to update guidelines to swiftly enable the implementation of UGT1A1 genotype-guided irinotecan dosing in routine oncology care.

Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC) with oxaliplatin as a palliative monotherapy for isolated unresectable colorectal peritoneal metastases: protocol of a Dutch, multicentre, open-label, single-arm, phase II study (CRC-PIPAC).

INTRODUCTION: Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide. However, little is known about its feasibility, safety, tolerability, efficacy, costs and pharmacokinetics in this setting. This study aims to explore these parameters in patients with isolated unresectable colorectal PM who receive repetitive ePIPAC-OX as a palliative monotherapy. METHODS AND ANALYSIS: This multicentre, open-label, single-arm, phase II study is performed in two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM. Eligible patients are adults who have histologically or cytologically proven isolated unresectable PM of a colorectal or appendiceal carcinoma, a good performance status, adequate organ functions and no symptoms of gastrointestinal obstruction. Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled ePIPAC-OX (92 mg/m2 body surface area (BSA)) with intravenous leucovorin (20 mg/m2 BSA) and bolus 5-fluorouracil (400 mg/m2 BSA) every 6 weeks. Four weeks after each procedure, patients undergo clinical, radiological and biochemical evaluation. ePIPAC-OX is repeated until disease progression, after which standard palliative treatment is (re)considered. The primary outcome is the number of patients with major toxicity (grade ≥3 according to the Common Terminology Criteria for Adverse Events v4.0) up to 4 weeks after the last ePIPAC-OX. Secondary outcomes are the environmental safety of ePIPAC-OX, procedure-related characteristics, minor toxicity, postoperative complications, hospital stay, readmissions, quality of life, costs, pharmacokinetics of oxaliplatin, progression-free survival, overall survival, and the radiological, histopathological, cytological, biochemical and macroscopic tumour response. ETHICS AND DISSEMINATION: This study is approved by an ethics committee, the Dutch competent authority and the institutional review boards of both study centres. Results are intended for publication in peer-reviewed medical journals and for presentation to patients, healthcare professionals and other stakeholders. TRIAL REGISTRATION NUMBER: NCT03246321, Pre-results; ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.