Chemotherapy and Chemoradiotherapy Studies in Oesophageal Cancer

The aim of this thesis was, first, to explore the use of preoperative chemoradiotherapy and palliative chemotherapy in the treatment of oesophageal cancer. Furthermore, the effects of a chemoradiotherapy regimen on histopathological and psychological and social level were studied. Chapter 2 provides a review of the literature on systemic treatment for oesophageal cancer. An overview is given for preoperative and postoperative chemotherapy, preoperative chemoradiotherapy, definitive chemoradiotherapy, and palliative chemotherapy. In Chapter 3 the efficacy and safety of preoperative chemoradiotherapy consisting of carboplatin and paclitaxel and concurrent radiotherapy for patients with resectable oesophageal cancer is studied. Chapter 4 describes the histopathological effects of the above mentioned chemoradiotherapy regimen and correlates the effect of specific pathologic and clinical findings to overall survival. In Chapter 5 the health related quality of life up to one year after surgery, in patients with oesophageal cancer treated with curative intent with neoadjuvant chemoradiotherapy consisting of the above mentioned regimen followed by oesophagectomy is evaluated. Finally, in Chapter 6 the analysis of a phase II study evaluating the safety and efficacy of the combination of oxaliplatin and capecitabine in patients with metastatic or local-regional unresectable carcinoma of the oesophagus, oesophagogastric junction, and cardia is given. In addition, the effect of this regimen of the patients’ well-being is evaluated by performing a quality of life analysis on these patients during the treatment. The studies described in this thesis are summarized in Chapter 7. Furthermore, potential directions for future studies are addressed

Irinotecan-Induced Toxicity:A Pharmacogenetic Study Beyond UGT1A1

Background and objective: Side effects of irinotecan treatment can be dose limiting and may impair quality of life. In this study, we investigated the correlation between single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in the irinotecan metabolism and transport, outside UGT1A1, and irinotecan-related toxicity. We focused on carboxylesterases, which are involved in formation of the active metabolite SN-38 and on drug transporters. Methods: Patients who provided written informed consent at the Erasmus Medical Center Cancer Institute to the Code Geno study (local protocol: MEC02-1002) or the IRI28-study (NTR-6612) were enrolled in the study and were genotyped for 15 SNPs in the genes CES1, CES2, SLCO1B1, ABCB1, ABCC2, and ABCG2. Results: From 299 evaluable patients, 86 patients (28.8%) developed severe irinotecan-related toxicity. A significantly higher risk of toxicity was seen in ABCG2 c.421C&gt;A variant allele carriers (P = 0.030, OR 1.88, 95% CI 1.06–3.34). Higher age was associated with all grade diarrhea (P = 0.041, OR 1.03, 95% CI 1.00–1.06). In addition, CES1 c.1165-41C&gt;T and CES1 n.95346T&gt;C variant allele carriers had a lower risk of all-grade thrombocytopenia (P = 0.024, OR 0.42, 95% CI 0.20–0.90 and P = 0.018, OR 0.23, 95% CI 0.08–0.79, respectively). Conclusion: Our study indicates that ABCG2 and CES1 SNPs might be used as predictive markers for irinotecan-induced toxicity.</p

Treatment of Inguinal Lymph Node Metastases in Patients with Rectal Adenocarcinoma

Background Inguinal lymph node metastases (ILNM) from rectal adenocarcinoma are rare and staged as systemic disease. This study aimed to provide insight into the treatment and prognosis of ILNM from rectal adenocarcinoma. Methods All patients with a diagnosis of synchronous or metachronous ILNM from rectal adenocarcinoma between January 2005 and March 2017 were retrospectively reviewed. Result

Concomitant intraperitoneal and systemic chemotherapy for extensive peritoneal metastases of colorectal origin: protocol of the multicentre, open-label, phase I, dose-escalation INTERACT trial

INTRODUCTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases of colorectal origin with a low/moderate abdominal disease load. In case of a peritoneal cancer index (PCI) score >20, CRS-HIPEC is not considered to be beneficial. Patients with a PCI >20 are currently offered palliative systemic chemotherapy. Previous studies have shown that systemic chemotherapy is less effective against peritoneal metastases than it is against haematogenous spread of colorectal cancer. It is suggested that patients with peritoneal metastases may benefit from the addition of intraperitoneal chemotherapy to systemic chemotherapy. Aim of this study is to establish the maximum tolerated dose of intraperitoneal irinotecan, added to standard of care systemic therapy for colorectal cancer. Secondary endpoints are to determine the safety and feasibility of this treatment and to establish the pharmacokinetic profile of intraperitoneally administered irinotecan. METHODS AND ANALYSIS: This phase I, '3+3' dose-escalation, study is performed in two Dutch tertiary referral centres. The study population consists of adult pa