Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Surgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach. METHODS: This multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤ 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m2). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. DISCUSSION: The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. TRIAL REGISTRATION: Clinical Trials: NCT04927780. Registered June 16, 2021.

Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial.

BACKGROUND: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients. METHODS: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up. DISCUSSION: The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer. TRIAL REGISTRATION: Primary registry and trial identifying number: EudraCT: 2017-002036-17 . Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register - NL7094 , NL61961.078.17, MEC-2018-004.

[Dutch Institute for Healthcare Improvement guideline, "Treatment of breast cancer"]. / CBO-richtlijn 'Behandeling van het mammacarcinoom'.

The first Dutch evidence-based guideline for the treatment of breast cancer has been developed to realise the optimal care of breast cancer patients in the Netherlands. This was possible due to the close cooperation of the Dutch Institute for Healthcare Improvement [Dutch acronym: CBO] and the Dutch Consultative Committee on Breast Cancer [Dutch acronym: NABON]. A broad, multidisciplinary working group was appointed to develop the guideline. This group consisted of surgeons, radiotherapists, internists, pathologists, a radiologist, a nuclear medicine specialist, a plastic surgeon and a clinical geneticist, all of whom had been given a mandate to represent their respective professional societies. In addition to these medical specialists, there were physiotherapists, oncology nurses, psychologists, staff from comprehensive cancer centres and the Dutch Institute for Healthcare Improvement and representatives from the Dutch Breast Cancer Association. This CBO guideline is divided into seven chapters: local treatment of operable breast cancer, systemic adjuvant treatment, locoregionally advanced disease, follow-up, locoregional recurrence, metastasised disease, and the psychosocial aspects of breast cancer. Although the guideline is not intended as a set of instructions that must be rigidly adhered to, deviations from the guideline must be motivated, principally on the basis of published scientific information. To obtain insight into the actual use of the guidelines 'Screening and diagnostics' and 'Treatment of breast cancer' the work group advocates a nationwide prospective registration of all breast cancer patients, including follow-up. Steps to this end have been undertaken. In this way, the CBO guideline will contribute to a further optimisation of breast cancer care in the Netherlands.

[Primary and adjuvant radiochemotherapy of pancreatic carcinoma]. / Primäre und adjuvante Radiochemotherapie des Pankreaskarzinoms.

Pancreatic carcinoma is a type of cancer with an extremely poor prognosis. Surgery is the only curative option, and only possible in a minority of patients. After surgery the 5-year survival rate is approximately 25%. The role of radiochemotherapy in the treatment of locally advanced pancreatic cancer and in the adjuvant setting is discussed:--Locally advanced disease: Numerous studies are being performed to improve disease free survival in locally advanced disease. So far the combination of high dose radiotherapy and continuous infusion of 5-fluorouracil appears to be the best option. However, the potential gain is limited, and this should be weighed against the burden of treatment for patients with a very short life expectancy. New combinations are being investigated.--Adjuvant treatment: After radical surgery there is no standard adjuvant treatment. Four randomized trials were performed so far. In one of these only the role of chemotherapy was investigated. In the three other trials the radiochemotherapy applied was not optimal. Yet a trend for a survival benefit was seen in two of these trials, at least in the subgroup of pancreatic head cancer. One of the four trials appears to show a benefit from chemotherapy. These results warrant further investigation of the role of (optimal) radiochemotherapy, and the role of chemotherapy. In collaboration with the FFCD and GERCOR, the EORTC will start an international multicenter randomized phase III study comparing high dose radiotherapy and concomitant continuous infusion of 5-FU versus control after pancreatico-duodenectomy for pancreatic head cancer (22995/40992).