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Purpose To determine if women with breast cancer that undergo fertility preservation (FP), with or without hormonal stimulation, present with an increased risk of breast cancer recurrence. Methods A matched cohort study on women with breast cancer attempting to ensure FP in Stockholm from 1999 to 2013 [exposed women (n = 188), age-matched unexposed controls (n = 378)] was designed using the Stockholm regional data from the Swedish National Breast Cancer Quality Register. Breast cancer relapse rates [incidence rate ratio (IRR)] and 95% confidence interval (CI) were estimated using Cox regression and adjusted for potential confounding factors. Completeness of the registry at the time of the study was close to 99%. Results Most women attempted FP by hormonal stimulation treatment (n = 148, 79%) with the objective of freezing their eggs or embryos. A smaller group elected FP methods without hormone stimulation (n = 40, 21%). Women who received hormone stimulation did not present with a higher relapse rate than unexposed control women in a model adjusted for age and calendar period of diagnosis (IRR 0.59, 95% CI 0.34–1.04). The results remained virtually unchanged after adjustment for tumor size, estrogen receptor status, affected lymph nodes, and chemotherapy treatment (IRR 0.66, 95% CI 0.37–1.17). Conclusion Evidence was not found that fertility preservation, with or without hormonal stimulation, was associated with an increased risk of breast cancer recurrence. The high coverage rate of this population-based study supports the safe practice of fertility preservation in young women with breast cancer.

Purpose The number of women that perform fertility preservation (FP) before initiating chemotherapy for treatment of breast cancer is increasing. Our purpose was to investigate the safety of performance of fertility preservation with and without hormonal stimulation in the incidence rate of breast cancer relapse. Patients and methods The study was designed as a matched cohort study. Women who had undergone FP at the Reproductive Medicine clinic of Karolinska University Hospital (N=187), irrespective of whether hormonal stimulation was required or not, were considered exposed. For all exposed women, two age-matched women who had not undergone fertility preservation were identified in the Regional Breast Cancer Registry Stockholm-Gotland and the Swedish National Quality Registry for Breast Cancer (N=319). The proportional hazards assumption was evaluated by applying the Grambsch-Therneau test on the Schoenfeld residuals obtained from each model, respectively. When interpreting the test results, a significance level of 5% was used to determine statistical significance. Results In the exposed cohort, a higher proportion of women underwent FP with hormonal stimulation aiming at freezing eggs or embryos (81%, N=142), whereas only 19% underwent freezing of ovarian tissue or attempted egg retrieval without hormonal stimulation (N=35). The mean follow up time was 6.3 years (range: 1.5-17.8 years), and median follow-up: 5.7 years. There was no evidence of non-proportional hazards with respect to the effects of fertility preservation on the risk of relapse in the whole FP cohort, irrespective if the women underwent hormonal stimulation or not for FP, or of receptor status or tumour size at diagnosis. A stratified Cox regression model that allowed separate baseline hazard functions for each level for the investigation of the effect of number of involved lymph nodes was performed. In this model, the effect of fertility preservation on the risk of relapse was virtually unchanged (IRR: 1.02, 95% CI:0.56-1.84). Conclusion Fertility preservation either using hormone stimulation or not is unlikely to cause substantially increase recurrence risk of breast cancer, and irrespective of the receptor status, tumorur size of lymph node compromise. The incidence of breast cancer relapse after hormonal or non-hormonal fertility preservation was not different from that of matched controls from the Regional Breast Cancer Registry in this large cohort study. Citation Format: Rodriguez-Wallberg KA, Eloranta S, Krawiec K, Lissmats A, Liljegren A. Safety of fertility preservation indicated by a diagnosis of breast cancer: A Swedish registry-matched cohort study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-11-05.

Oral mucositis, a severe complication during chemo- and/or radiotherapy, is prevented with palifermin treatment, a recombinant human keratinocyte growth factor (KGF/FGF-7). The FGF family belongs to the larger family of heparin-binding growth factors. Because it has been shown that heparin modulates binding of KGF to the KGF receptor and subsequently affects cellular proliferation induced by the KGF mitogenic signal, it is critical to understand the drug-drug interactions between palifermin and heparin, particularly because of heparin's narrow therapeutic margin. Two studies were performed in healthy subjects to characterize the effect of palifermin on the pharmacodynamics of heparin (activated partial thromboplastin time) and evaluate the impact of heparin on the pharmacokinetics and pharmacodynamics (Ki67 staining of buccal mucosal tissue) of palifermin. Results demonstrated a pronounced pharmacokinetic interaction; heparin coadministration increased the palifermin AUC 4- to 5-fold and decreased its half-life by 40%-45%, suggesting an approximate 70%-80% decrease in palifermin clearance and volume of distribution. These changes in the pharmacokinetics of palifermin during coadministration of heparin, however, did not affect the pharmacodynamic effect of palifermin, or the anticoagulant activity of heparin, and did not lead to increased safety findings. Therefore, these results suggest that dose adjustments for heparin and palifermin are not warranted when administered concurrently.

Background: Data from clinical practice have only to a limited extent, been used routinely to monitor cancer patients initiated on new drugs. In this study of patients with cancer, focussing on prostate, breast, and skin cancer, two years of individual data from several registries was used to explore the possibilities to monitor patients with cancer. Methods: This study is based on a research database with more than 78 million records with person-linked diagnoses, drug treatment, and socioeconomic characteristics from eight national and regional registries, for patients with a recorded cancer diagnosis or treated with cancer drugs during 2001-2011. For this cross-sectional registry study 7,378 patients diagnosed with prostate, breast, or skin cancer during 2009-2010, were selected to assess patient characteristics, comorbidities and drug treatment. Results: Of the population selected from the Swedish Cancer Register with the three major diseases, 3,581 had prostate cancer, 2,760 had breast cancer, and 1,037 had skin cancer. The income was 70.1%, 62.9%, and 53.3% in the prostate, breast and skin cancer group, respectively. Urogenital- and cardiovascular diseases were common in both prostate (47.8% and 52.7%), and breast cancer (52.4% and 42.6%) patients. In skin cancer patients, other skin diagnoses were most common (50.7%) followed by cardiovascular disorders (48.3%). Cancer drugs, mainly mature, were received by 85.9% of patients with breast cancer, 32.4% of patients with prostate cancer, and 4.1% of patients with skin cancer. Additional tumour diagnoses for 5.2% of prostate cancer patients, 4.1% of breast cancer patients, and 17.3% of patients with skin cancer, were found in primary care data. Conclusion: Access to healthcare data, including primary care, and the opportunity to link records from multiple data sources by the Swedish personal identity number, allow the possibility to study treatment, disease pattern and characteristics in large cancer patient populations.

Item does not contain fulltext This randomized-controlled trial studied the efficacy of palifermin in a chemotherapy-only, high-dose Melphalan (HDM) transplant setting, to reduce oral mucositis (OM) and its sequelae measured by patient-reported outcomes (PRO) and medical resource use. Palifermin, relative to placebo was given either pre-/post-HDM or pre-HDM in patients with multiple myeloma (MM) undergoing auto-SCT at 39 European centers. Oral cavity assessment (WHO) and PRO questionnaires (oral mucositis daily questionnaire (OMDQ) and EQ 5D) were used in 281 patients (mean age 56, +/-s.d.=8 years). 57 patients received placebo. One hundred and fifteen subjects were randomized to pre-/post-HDM receiving palifermin on 3 consecutive days before HDM and after auto-SCT and 109 patients were randomized to pre-HDM, receiving palifermin (60 mug/kg/day) i.v. for 3 consecutive days before HDM. There was no statistically significant difference in maximum OM severity. Severe OM occurred in 37% (placebo), 38% (pre-/post-HDM) and 24% (pre-HDM) of patients. No significant difference was observed with respect to PRO assessments or medical resource use, but more infections and fever during neutropenia were reported in pre-/post-HDM vs placebo (for example, 51 and 26%). To conclude, palifermin was unable to reduce OM or OM-related patient's burden in MM transplant patients. 01 juli 2013

Abstract 904 Palifermin administered pre and post radiochemotherapy conditioning has previously been shown to significantly reduce the incidence and duration of severe oral mucositis (OM) in patients undergoing autologous stem cell transplantation (ASCT). This randomized clinical trial (RCT) aimed to study the efficacy and safety of palifermin when administered in two different dosing regimens in a chemotherapy-only conditioning setting. The efficacy of palifermin relative to placebo was investigated with palifermin given either pre/post high-dose melphalan (HDM) or pre HDM only in patients with multiple myeloma (MM) undergoing ASCT. Assessment of oral mucositis was primarily based on WHO grades (0/1, 2, 3 or 4) and safety primarily on adverse event (AE) reporting. 281 patients (mean age 56 ± 8 years) were enrolled at 39 centers; 224 patients were randomized to receive palifermin and 57 patients to receive placebo. In the palifermin group, 109 patients were randomized to the pre-only arm, receiving palifermin (60 μg/kg/day) iv for 3 consecutive days before HDM and 115 subjects were randomized to the pre/post arm receiving palifermin on 3 consecutive days before HDM and again on 3 consecutive days after ASCT. The number of subjects actually receiving study drug in the these two arms was 109 and 111, respectively. Assessments of OM and safety were made daily until 32 days post transplant or hospital discharge. There was no difference in maximum severity of OM between placebo and palifermin administered pre/post HDM (odds ratio: 0.7 [CI: 0.4, 1.3]) or pre HDM (odds ratio: 1.2 [CI: 0.6, 2.4]). Severe OM (WHO grade 3 and 4) occurred in 37% (placebo), 38% (pre/post-HDM) and 24% (pre-HDM) of the patients. A total of 275 patients (99.3%) experienced at least 1 AE during the study. There were more serious AEs and AEs reported as treatment related by the investigators for patients in the pre/post HDM arm, and less in the pre-HDM arm but still more than in the placebo arm. Overall, no statistically significant differences were observed between placebo and either the palifermin pre-post HDM arm or pre-only HDM arm for maximum severity of OM in this clinical setting with a chemotherapy conditioning regimen of short duration and a comparably low incidence of severe oral mucositis. The pre-only group, however, showed a numerically better result than placebo for the primary and most of the secondary efficacy endpoints. Patients treated with palifermin in the pre HDM arm experienced a more favorable safety profile than the pre/post HDM arm. Possible explanations for the apparent discrepancy compared to previously published trials might be differences in high dose chemotherapy and/or the shorter time interval between the pre and post doses in this study. The impact of the timing of the palifermin post-dose in relation to the pre-dose and in relation to the onset of manifest OM and pathogenesis thus needs to be further explored. Disclosures: Blijlevens: Biovitrum: Consultancy. de Chateau:Biovitrum : Employment. Lissmats:Biovitrum: Employment. Niederwieser:Biovitrum: Consultancy.