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Background: The AIO KRK-0104 randomised phase II trial investigated the efficacy and safety of two capecitabine-based regimens: combination of capecitabine and irinotecan (CAPIRI) plus cetuximab (CAPIRI-C) and combination of capecitabine with oxaliplatin (CAPOX) plus cetuximab (CAPOX-C) in the first-line treatment of metastatic colorectal cancer (mCRC). Treatment-related skin toxicity (ST) was evaluated separately for capecitabine and cetuximab. The present analysis investigates the correlation of capecitabine-attributed ST (Cape-ST) and parameters of treatment efficacy.Methods: Patients with mCRC were randomised to cetuximab (400 mg m(-2), day 1, followed by 250 mg m(-2) weekly) plus CAPIRI (irinotecan 200 mg m(-2), day 1; capecitabine 800 mg m(-2), twice daily, days 1-14, every 3 weeks), or cetuximab plus CAPOX (oxaliplatin 130 mg m(-2), day 1; capecitabine 1000 mg m(-2), twice daily, days 1-14, every 3 weeks).Results: Of 185 recruited patients, 149 (CAPIRI-C, n=78; CAPOX-C, n=71) received study treatment beyond the first tumour assessment and were evaluable for efficacy. Capecitabine-attributed ST, predominantly hand-foot syndrome, was observed in 32.2% of patients. Capecitabine-attributed ST grade 1-3 was associated with a significantly higher disease control rate (DCR) (97.9 vs 86.1%, P=0.038) compared with grade 0 toxicity. Moreover, Cape-ST grade 1-3 related to a markedly longer progression-free survival (PFS) (9.9 vs 5.6 months, P<0.001) and overall survival (OS) (32.8 vs 22.4 months, P=0.008). Separate analyses of treatment arms indicated that the effect of Cape-ST on PFS remained significant for both arms, whereas the effect on OS remained apparent as a strong trend.Conclusion: This analysis supports the hypothesis that for the evaluated regimens, a correlation exists between Cape-ST and treatment efficacy regarding DCR, PFS, and OS. [ABSTRACT FROM AUTHOR]

Background: Specialized outpatient palliative care (SAPV) is a component of palliative care in Germany, which assists approximately 10% of palliative patients. The majority of these patients have a malignant disease and are at increased risk of complications or severe infection. Antibiotic stewardship (ABS) measures are implemented to optimize antibiotic administration; however, there is little data available in this area, particularly for SAPV. Therefore, we examined the extent to which ABS measures can be meaningfully used or implemented in SAPV., Methods: After establishing a corresponding interview guide, 15 experts from specialized areas were interviewed on this subject by the Institute for Market Research in Healthcare Munich (IMIG) through audio-registered individual interviews. The interviews were analyzed using the qualitative content analysis method according to Mayring., Results: All 15 experts participated. The primary benefits cited were greater safety in the prescription and decision-making process for antibiotics in the areas of SAPV and improved quality of life. The implementation of continuous ABS measures for SAPV was considered difficult in some cases and linked to certain prerequisites, such as supportive advice from existing systems. The possibility of further training for SAPV members in the area of ABS was considered particularly advantageous., Conclusions: The implementation of ABS measures in SAPV is feasible in principle; however, it is difficult to implement under the current conditions. Close cooperation with an existing external ABS expert/team will be helpful. This will provide more security for a small, but relevant proportion of SAPV patients, and for the SAPV team treating them., Competing Interests: Declarations. Ethics approval and consent to participate: After consultation with the Ethics Committee of the University of Regensburg, no professional advice and consequently no vote by the Ethics Committee was required for the present study in accordance with Sect. 15 of the Professional Code of Conduct for Physicians in Bavaria. Consent for publication: Not applicable. Competing interests: U.K., J.S., and U.VK. declare no competing interests; F.H. has received lecture fees from Pfizer, and travel expenses and congress fees have been covered by Tillotts Pharma and Gilead Sciences; F.K. has conducted consulting work for Elsevier, Astellas, GSK, MSD, Novartis, Pierre Fabre, Sanofi, and Servier., (© 2024. The Author(s).)

Long-term data of chronic lymphocytic leukemia (CLL) patients with favorable risk who were treated with fludarabine, cyclophosphamide, and rituximab (FCR) within clinical trials show good efficacy. We here report long-term data collected within the GCLLSG registry. Altogether, 417 CLL patients who received first-line treatment with FCR were analyzed, of which 293 (70.3%) were treated outside of clinical trials. The median observation time from first-line was 95.8 (interquartile range 58.7-126.8) months. Focusing on data of 194 (46.5%) patients who received FCR first-line treatment after 2013 (start of data collection within GCLLSG registry), responses were documented in 85% of the patients, non-responses in 15%, and for 3.6% the assessment was missing. Median event-free survival (EFS, time until disease progression, subsequent treatment, or death) was 60.2 months with a 5-year EFS-rate of 50.6%. Patients with higher-risk disease, characterized by unmutated IGHV (N = 78), had a median EFS of 45.4 months with a 5-year EFS rate of 36.3%, while the median EFS was 77.5 months with a 5-year EFS rate of 60.3% in patients with mutated IGHV (N = 40). Median overall survival was not reached with a 5-year survival rate of 92.7%. In summary, first-line FCR was associated with long EFS, especially in patients exhibiting a mutated IGHV status., (© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: Currently, a conclusive experience on the uniform implementation and benefits of day hospice structures and interventions is lacking in Germany. The following questions should be clarified: (1) Which structural conditions and interventional measures should be established in day hospices from the point of view of patients, relatives, and specialist staff?; (2) Are the planned structures or interventions feasible and implementable under real conditions and accepted by patients, relatives, and staff?; (3) How can a final implementation and intervention catalog for day hospices be designed?; (4) Is this final catalog of services feasible, reasonable, economical, and effective under everyday conditions in day hospices?, Methods: We planned to perform a multistage investigation, guided by the Medical Research Council Framework for the development and evaluation of complex interventions. In Stage 1, an initial theoretical construct on structures and interventions will be established through an extensive literature and guideline review on day hospices and through qualitative interviews. In a nominal group process, we will create a catalog of offers. In Stage 2, feasibility testing is conducted in a single-day hospice under real-life conditions using quantitative quality indicators and qualitative interviews. Structures and interventions can be adapted here if necessary. In a second nominal group process, a final structure and offer catalog is created, which is then implemented in Stage 3 in the day hospice under investigation and evaluated under real daily conditions through a process and effectiveness test. For this purpose, qualitative and quantitative quality indicators will be used and a comparative cohort of patients who are not cared for in the day hospice - but in the same network structure (oncology-palliative care network Lower Bavaria) - is examined., Discussion: Finally, the initial statements on the reasonable and realizable structures or interventions in day hospices and their benefits in daily real-life conditions as well as possible optimization processes shall be made., Trial Registration: The study was retrospectively registered in the German Clinical Trials Register (DRKS-ID DRKS00031613, registration date April 04, 2023) and the display portal of the Center for Clinical Trials of the University Hospital Regensburg (Z-2022-1734-6, registration date July 01, 2023)., (© 2024. The Author(s).)

Introduction: In further-line mCRC treatment, median progression-free survival (PFS) is rather short, and many patients do not benefit from any antitumor treatment and should therefore be treated according to best-supportive care. A risk score based on standard laboratory values using markers of tumor inflammation aims to define a patient cohort with high treatment benefit and might offer insights into tumor biology. As regorafenib has been dropped off the German market due to an unfavorable risk-benefit ratio, patient selection is key for any further-line treatment option., Methods: We used Cox regression analysis to determine laboratory markers that are independent prognostic factors of OS and PFS outcome. The influence of these variables was weighted using an estimator, which was calculated using Cox regression analysis. The estimators were implemented as multiplication factors, resulting in a risk score. A cut-off value for the resulting risk values was then determined via Cox regression analysis resulting in a low- and high-risk subgroup., Results: Using data of 82 patients, a risk score identifying long-term survival in patients with last-line mCRC treatment could be calculated. The following parameters were associated with significantly longer survival in multivariate analysis: NLR ≤5 (p = &lt;0.001), AP ≤200 U/L (p = 0.001), CRP ≤3.2 mg/dL (p = &lt;0.001). The following estimator values were used to calculate a risk score: NLR: 0.132 (p = 0.046), AP: 0.004 (p = 0.014), and CRP: 0.032 (p = 0.039). Implementing the estimators as multiplication factors yielded the following risk score: 0.132*NLR + 0.004*AP + 0.032*CRP = Risk value. Cox regression resulted in low- and high-risk subgroups with risk values below and above 1.4, respectively. In the group with a low-risk score (&lt;1.4), patients had a median OS of 10.5 months after initiating regorafenib. Patients with a high-risk score (&gt;1.4) survived only 3.3 months after starting therapy with regorafenib (n = 43, p &lt; 0.001, HR = 3.76)., Conclusions: The presented composite risk score stratifies patients into two prognostic subgroups characterized by standard laboratory values. Patients with signs of systemic inflammation characterized by elevated NLR, AP, and CRP have a high composite risk score and a significant shorter overall survival. Although this score needs to be prospectively validated in larger cohorts, it may be used to stratify patients suitable for further-line treatment studies., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

The Onko-Nexus ("Caretaker-Project"), sponsored by the Bavarian Ministry for Health and Nursing, is dedicated to improving the outpatient/hospitalized care interface issue for patients with highly complex malignant diseases requiring inpatient care in a university hospital. A total of 26 patients were recruited during the 3-year period of the project. The patients were managed and supported by 2 "Caretakers" (physician assistants), one from the outpatient unit and one working in the wards. Additionally, the university hospital provided a special consultation hour in an oncological private practice close to patient's home. After completion of the project, 9 patients and the 2 "Caretakers" were interviewed via guided qualitative interviews. The main benefits for the patients were intensive support, avoiding long journeys and the close contact between hospital and private practice. The project had a clear positive effect on the patients' quality of life., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: Oral tyrosine kinase inhibitor (TKI) therapies are becoming increasingly more important in the treatment of malignant diseases. Monitoring with focus on adherence, side effects and interactions poses new challenges for medical care. The role and capabilities of family doctors in the care of TKI patients are yet unclear and should be uncovered in a nationwide survey., Methods: From April to July 2016, 3,000 family doctors in Germany were asked to complete a written questionnaire regarding their capabilities for co-supervision of TKI patients., Results: The response rate was 18% (n=553). The peak age was between 50 and 60 years. 81% were specialists in general medicine, 14% specialists in internal medicine and 5% general practitioners. 98% cared for no or less than 10 TKI patients per quarter. Knowledge of side effects and interaction potential of TKIs was low in over 90%. 83% preferred monitoring by the treating oncologist and 93% felt uncertain about treatment monitoring. The control of adherence was of little importance in 66%. The number of treated TKI patients had a significant impact on knowledge and opportunities for treatment monitoring. There was a significant correlation between knowledge about TKIs and confidence in treatment monitoring. In general, younger doctors tended to be more confident in treatment monitoring, and specialists in internal medicine tended to have more knowledge than specialists in general medicine general practitioners and general practitioners., Discussion: Currently, the low number of TKI patients, little knowledge about TKI, and the desire for specialist care are limiting the possibilities of co-caring for TKI patients by family doctors., Conclusion: Although family doctors are generally motivated to care for tumor patients, routine treatment controls of TKI patients conducted by family doctors seem hardly possible at the moment and should currently remain with the specialist., (Copyright © 2020. Published by Elsevier GmbH.)

Background: There is controversy regarding the practical implementation of symptom-focused oncological cancer therapies to hospice residents. In this study, we aim to analyse the use and indication of supportive-oncological cancer therapies in hospices., Methods: We conducted a retrospective survey of all residents of two hospice centres in the government district of Lower Bavaria, Germany. Hospice 1 (H1) was a member of an oncological-palliative medical network, and hospice 2 (H2) was independently organized. The evaluation period was the first 40 months after the opening of the respective hospice care centre. Demographical and epidemiological data as well as indications and type of supportive-oncological cancer therapies were recorded. A descriptive analysis and statistical tests were performed., Results: Of the 706 residents, 645 had an underlying malignant disease. The average age was 72 years and the mean residence time was 28 days. The most frequent cancer types were gastrointestinal cancers, gynaecological cancers and bronchial carcinomas. Overall 39 residents (33 in H1 and 6 in H2, p < 0.01) received symptom-focused oncological cancer therapy. The average age of these residents was 68 years, and the mean residence time was 55 days. The most common therapeutic indications were dyspnoea and pain. The most common symptom-focused oncological cancer therapies were bisphosphonates, transfusions (erythrocyte- and platelet- concentrates), radiotherapy and anti-proliferative drugs (chemotherapy, anti-hormonal- and targeted- therapies). Patients with therapy lived significantly longer than patients without therapy (p < 0.01)., Conclusions: Symptom-focused oncological cancer therapies can be implemented in hospices; however, their implementation seems to require certain structural and organizational prerequisites as well as careful patient selection. As a palliative medical approach, the focus is to ameliorate the symptoms and not prolong life. Symptom-focused oncology treatment could be a further and important part for the therapy of hospice patients in the future.

Background: Oral antiproliferative therapies have become increasingly important in the treatment of tumors. To ensure patient safety, medical care is focused on adherence and side effects., Objectives: To meet increased personnel and time requirements, delegation of tasks to nonmedical specialists (NMS) may be a solution; however, presently, little is known about the options in Germany., Method: At least 3,300 members of the German Society for Hematology and Medical Oncology (DGHO), 580 members of the Professional Association of Office-Based Hematologists and Oncologists in Germany (BNHO), and 1,500 members of the Conference on Oncology Nursing and Pediatric Nursing (KOK) were contacted via a web-based survey. The survey focused on the feasibility of oncology nurse consultation as an additional consulting service for patients undergoing oral tumor therapy., Results: In total, 255 (physicians) and 206 (NMS) questionnaires were evaluable; 90.9% of the physicians were hematologists/oncologists, 87.8% advocated oncology nurse consultation, 34.1% had previously implemented/scheduled such consultations, 58.3% of the NMS were nursing staff, 46.1% had advanced training in oral tumor therapy, 94.2% were interested in further qualifications, 37.8% worked at facilities with established/planned nurse consultations, and 62.1% personally conducted/preferred conducting consultations., Conclusions: Throughout Germany, there seems to exist a group of qualified NMS who are motivated to provide care to patients undergoing oral tumor therapy. Particular physicians actively support these nurse consultations. Extensive implementation of delegation concepts in standard care of patients undergoing oral tumor therapy is not yet underway., (© 2019 S. Karger AG, Basel.)

Background: In 2011, a specialized palliative home care was introduced in the counties of Landshut and Dingolfing., Objectives: The aim of the current survey was to evaluate the cooperation, acceptance and need of palliative measures for patients particulary from the general practitioner's perspective., Methods: From January to March 2015, 198 general practitioners from the counties of Landshut and Dingolfing were contacted with questionnaires. The questionnaires consisted of 16 questions covering five different issues, and drew upon the practical experiences of the authors and earlier surveys from the literature. The questionnaires were sent by post containing a self-addressed and postpaid envelope., Results: Completed questionnaires from 40 out of 198 contacted general practitioners (33 % female and 53 % male). Of these 85 % had cooperated with a SAPV team, 23 % had taken part in training for palliative medicine, 10 % intended to acquire a qualification and 10 % could imagine working in a SAPV team. In addition, 75 % stated that hospitalizations were avoided through the use of SAPV while 73 % felt that time and costs were saved for their own practices. The majority of general practitioners were satisfied with the work provided by the SAPV and the cooperation. Regarding additional palliative care for geriatric patients, 60 % believed that this was sensible. One main critique was that the information about including a patient in the SAPV program was transferred to the general practitioner too late., Conclusion: The current data show that general practitioners recognize the need for palliative medicine skills and predominately welcome the work of a specialized palliative care team in treating their patients. However, close cooperation and communication is necessary for a successful network between generalists and specialists in palliative care.

Perioperative treatment is a standard of care in locally advanced gastroesophageal cancer (GEC) (gastric adenocarcinoma and gastroesophageal junction (GEJ) adenocarcinoma). While preoperative treatment can be applied to the majority of patients, postoperative chemotherapy can be given only to a fraction. The NeoFLOT-study therefore investigates the application of prolonged neoadjuvant chemotherapy (NACT). Patients with T3, T4, and/or node-positive adenocarcinoma (GEC) were eligible for this multicenter phase II trial. NACT consisted of 6 cycles of oxaliplatin 85 mg/m(2) , leucovorin 200 mg/m(2) , 5-fluorouracil 2600 mg/m(2) and docetaxel 50 mg/m(2) (FLOT) applied q 2 wks. Application of adjuvant chemotherapy was explicitly not part of the protocol. R0-resection rate was evaluated as a primary endpoint. Of 59 enrolled patients, 50 patients underwent surgery and were assessable for the primary endpoint. R0-resection rate was 86.0% (43/50). Pathologic complete response (pCR) was 20.0% (10/50) and a further 20% (10/50) of patients achieved near complete histological remission (<10% residual tumor). Among these very good responders, 85% (17/20) had intestinal type tumors, 10% (2/20) had diffuse and 5% (1/20) had mixed type tumors. After 3 cycles of NACT, 6.9% (4/58) of patients developed progressive disease. Median disease-free survival was 32.9 months. The 1-year survival-rate was 79.3%. Grade 3-4 toxicities included neutropenia 29.3%, febrile neutropenia 1.7%, diarrhea 12.1% and mucositis 6.9%. This study indicates that intensified NACT with 6 cycles of FLOT is highly effective and tolerable in resectable GEC. Very good response (pCR and <10% residual tumor) was predominantly observed in patients with intestinal type tumors., (© 2014 UICC.)

Background: Biosimilars are similar but non-identical versions of existing biological drugs. The HEXAFIL study was an observational study that assessed the clinical usage, safety and efficacy of the biosimilar filgrastim in routine clinical practice in Germany., Patients and Methods: A total of 1,337 cancer patients received the biosimilar filgrastim for primary prophylaxis (PP), secondary prophylaxis (SP) or interventional treatment (TX) plus chemotherapy. Data including neutropenic complications and adverse events (AEs) were documented for up to 3 consecutive cycles., Results: In cycle 1, 44.9% of the patients received the biosimilar filgrastim as PP, 31.0% as SP, and 23.6% as TX. Approximately 90% of the patients required no modifications to their chemotherapy regimen, with lower rates among the PP/SP versus the TX patients. Neutropenic complications occurred in 7.9%, 6.9%, and 3.9% of the patients (cycles 1, 2, and 3, respectively). Only 1.8% of the patients experienced febrile neutropenia during cycle 1. Earlier and longer filgrastim treatment reduced grade 3/4 leukopenia and neutropenic complications. The observed safety/tolerability profile was as expected; the most common AE (4.3%) was musculoskeletal back/bone pain., Conclusion: In this observational real-life study of clinical practice, the biosimilar filgrastim was effective and well tolerated, with results consistent with those reported in phase II and phase III trials. © 2015 S. Karger GmbH, Freiburg.

Background: Cetuximab and bevacizumab have both been shown to improve outcomes in patients with metastatic colorectal cancer when added to chemotherapy regimens; however, their comparative effectiveness when partnered with first-line fluorouracil, folinic acid, and irinotecan (FOLFIRI) is unknown. We aimed to compare these agents in patients with KRAS (exon 2) codon 12/13 wild-type metastatic colorectal cancer., Methods: In this open-label, randomised, phase 3 trial, we recruited patients aged 18-75 years with stage IV, histologically confirmed colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, an estimated life expectancy of greater than 3 months, and adequate organ function, from centres in Germany and Austria. Patients were centrally randomised by fax (1:1) to FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab (using permuted blocks of randomly varying size), stratified according to ECOG performance status, number of metastatic sites, white blood cell count, and alkaline phosphatase concentration. The primary endpoint was objective response analysed by intention to treat. The study has completed recruitment, but follow-up of participants is ongoing. The trial is registered with ClinicalTrials.gov, number NCT00433927., Findings: Between Jan 23, 2007, and Sept 19, 2012, 592 patients with KRAS exon 2 wild-type tumours were randomly assigned and received treatment (297 in the FOLFIRI plus cetuximab group and 295 in the FOLFIRI plus bevacizumab group). 184 (62·0%, 95% CI 56·2-67·5) patients in the cetuximab group achieved an objective response compared with 171 (58·0%, 52·1-63·7) in the bevacizumab group (odds ratio 1·18, 95% CI 0·85-1·64; p=0·18). Median progression-free survival was 10·0 months (95% CI 8·8-10·8) in the cetuximab group and 10·3 months (9·8-11·3) in the bevacizumab group (hazard ratio [HR] 1·06, 95% CI 0·88-1·26; p=0·55); however, median overall survival was 28·7 months (95% CI 24·0-36·6) in the cetuximab group compared with 25·0 months (22·7-27·6) in the bevacizumab group (HR 0·77, 95% CI 0·62-0·96; p=0·017). Safety profiles were consistent with the known side-effects of the study drugs. The most common grade 3 or worse adverse events in both treatment groups were haematotoxicity (73 [25%] of 297 patients in the cetuximab group vs 62 [21%] of 295 patients in the bevacizumab group), skin reactions (77 [26%] vs six [2%]), and diarrhoea (34 [11%] vs 40 [14%])., Interpretation: Although the proportion of patients who achieved an objective response did not significantly differ between the FOLFIRI plus cetuximab and FOLFIRI plus bevacizumab groups, the association with longer overall survival suggests that FOLFIRI plus cetuximab could be the preferred first-line regimen for patients with KRAS exon 2 wild-type metastatic colorectal cancer., Funding: Merck KGaA., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: This non-interventional surveillance study (NIS) collected data on the quality of life (QoL) of patients treated with capecitabine as mono- or combination chemotherapy in an outpatient setting., Methods: Capecitabine was administered orally for 14 days of each 21-day cycle. The main parameters of interest were QoL, compliance, patient and physician satisfaction, handling of hand-foot syndrome (HFS), and efficacy. The statistics were descriptive; some differences were compared using confidence intervals (CIs)., Results: 735 patients from 161 centers received at least 1 dose of capecitabine. The median duration of observation was 5.5 months overall. The QoL global score was 53% (mean from the entire study population at all times), without any correlation to HFS. The overall response rate (ORR) was 35.1%, and the disease control rate (DCR) 64.4%. The median progression-free survival (PFS) was overall 6.81 months (95% CI 6.32-7.63 months) and it was significantly higher in patients with HFS (8.4 months, 95% CI 7.5-9.2 months, hazard ratio (HR) 0.60; p < 0.0001). The safety and tolerability of capecitabine were considered acceptable. The HFS incidence (all grades) was 27.1%., Conclusions: Capecitabine had a favorable risk-benefit relation in outpatient therapy. The QoL remained stable over the course of the investigation, indicating good compliance. HFS was a strong predictor of longer PFS and had no negative impact on the global QoL., (© 2014 S. Karger GmbH, Freiburg.)

Objective: AIO-PK0104 investigated two treatment strategies in advanced pancreatic cancer (PC): a reference sequence of gemcitabine/erlotinib followed by 2nd-line capecitabine was compared with a reverse experimental sequence of capecitabine/erlotinib followed by gemcitabine., Methods: 281 patients with PC were randomly assigned to 1st-line treatment with either gemcitabine plus erlotinib or capecitabine plus erlotinib. In case of treatment failure (eg, disease progression or toxicity), patients were allocated to 2nd-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was time to treatment failure (TTF) after 1st- and 2nd-line therapy (TTF2; non-inferiority design). KRAS exon 2 mutations were analysed in archival tumour tissue from 173 of the randomised patients., Results: Of the 274 eligible patients, 43 had locally advanced and 231 had metastatic disease; 140 (51%) received 2nd-line chemotherapy. Median TTF2 was estimated with 4.2 months in both arms; median overall survival was 6.2 months with gemcitabine/erlotinib followed by capecitabine and 6.9 months with capecitabine/erlotinib followed by gemcitabine, respectively (HR 1.02, p=0.90). TTF for 1st-line therapy (TTF1) was significantly prolonged with gemcitabine/erlotinib compared to capecitabine/erlotinib (3.2 vs 2.2 months; HR 0.69, p=0.0034). Skin rash was associated with both TTF2 (rash grade 0/1/2-4:2.9/4.3/6.7 months, p<0.0001) and survival (3.4/7.0/9.6 months, p<0.0001). Each arm showed a safe and manageable toxicity profile during 1st- and 2nd-line therapy. A KRAS wild-type status (52/173 patients, 30%) was associated with an improved overall survival (HR 1.68, p=0.005)., Conclusion: Both treatment strategies are feasible and demonstrated comparable efficacy; KRAS may serve as biomarker in patients with advanced PC treated with erlotinib.

To date, only limited toxicity data are available for the combination of erlotinib with either capecitabine or gemcitabine as front-line therapy for advanced pancreatic cancer. Within a randomized phase III trial, 281 treatment-naive patients were randomly assigned between capecitabine (2000 mg/m/day, for 14 days, once every 3 weeks) plus erlotinib (150 mg/day, arm A) and gemcitabine (1000 mg/m as a 30-min infusion) plus erlotinib (150 mg/day, arm B). In case of treatment failure, patients were crossed over to a second-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was the time to treatment failure of second-line therapy (TTF2). This interim analysis of toxicity contains safety data from the first 127 randomized patients. During first-line therapy, patients received a median number of three treatment cycles (range 0-13) in both the arms. Regarding chemotherapy, a treatment delay was observed in 12% of the cycles in arm A and in 22% of the cycles in arm B. Dose reductions of the cytostatic drug were performed in 18 and 27% of treatment cycles, respectively. Erlotinib dose reductions were performed in 6 and 11% of all cycles. Grade 3/4 hematological toxicity was <10% in both the arms; major grade 3/4 toxicities in arms A and B were diarrhea (9 vs. 7%), skin rash (4 vs. 12%), and hand-foot syndrome (7 vs. 0%). No treatment-related death was observed. In conclusion, this interim safety analysis suggests that treatment with erlotinib 150 mg/day is feasible in combination with capecitabine or gemcitabine.