Norbert Marschner

Double-blind randomised trial of the antiemetic efficacy and safety of ondansetron and metoclopramide in advanced breast cancer patients treated with epirubicin and cyclophosphamide

Ondansetron was compared with metoclopramide for antiemetic efficacy in a randomised double-blind trial in 122 patients with advanced breast cancer. All patients were treated with epirubicin (greater than 50 mg/m2) and cyclophosphamide (greater than 500 mg/m2). 50 patients receiving ondansetron and 60 with metoclopramide were considered evaluable. Ondansetron was at least as effective as metoclopramide in the control of vomiting and nausea. The percentage of patients with complete plus major control was 72% (59-85%) vs. 61% (48-74%) on day 1 (P = 0.230) and 79% (67-91%) vs. 66% (53-78%) on days 2-3 after chemotherapy (P = 0.122). Over the 3-day study period, nausea was absent or mild in 60% of the patients treated with ondansetron, compared to 45% given metoclopramide (P = 0.064). No major drug-related side-effects were reported. 1 patient receiving ondansetron experienced gastrointestinal disturbance and headache. Episodes of diarrhoea, fever, hyperkinetic syndrome, fatigue, restlessness and migraine with vomiting were reported by 5 patients treated with metoclopramide. None of the changes in the biochemical or haematological parameters was attributed to the antiemetic treatments.

Survival of Patients With Advanced or Metastatic Renal Cell Carcinoma in Routine Practice Differs From That in Clinical Trials-Analyses From the German Clinical RCC Registry.

Micro‐Abstract A total of 732 prospectively recruited German patients with metastatic renal cell carcinoma were classified as either “trial‐eligible” or “trial‐ineligible” in accordance with the common exclusion criteria for clinical trials. The “trial‐ineligible” patients had shorter progression‐free and overall survival compared with the “trial‐eligible” patients, whose outcomes were comparable with those from clinical trials. Physicians should be aware of these differences when discussing the treatment options and outcome expectations with patients. Introduction: Because “real‐life” patients often do not meet the strict eligibility criteria of clinical trials, we assessed the trial eligibility of patients with advanced or metastatic renal cell carcinoma (mRCC) in routine practice and compared the survival of “trial‐ineligible” and potentially “trial‐eligible” patients. Patients and Methods: The present prospective, multicenter German cohort study is recruiting patients from 110 oncology/urology outpatient centers and hospitals at initiation of systemic first‐line treatment. The demographic, clinical, treatment, and survival data were collected. We defined patients as “trial‐ineligible” when ≥ 1 exclusion criterion (Karnofsky performance status < 80%, hemoglobin less than the lower limit of normal, non–clear cell carcinoma histology) was documented. Otherwise, the patients were considered “trial‐eligible”. Results: Of 732 patients included, 57% were classified as “trial‐ineligible”. Overall, the median first‐line progression‐free survival (PFS) was 7.9 months (95% confidence interval [CI], 6.9‐8.9 months). The median first‐line PFS of “trial‐eligible” and “trial‐ineligible” patients was 11.0 months (95% CI, 9.6‐13.1 months) and 5.3 months (95% CI, 4.6‐6.5 months), respectively. The median OS of the “trial‐eligible” and “trial‐ineligible” patients was 26.0 months (95% CI, 22.1‐29.7 months) and 12.6 months (95% CI, 10.6‐15.8 months), respectively. Conclusion: Our data suggest that patients in routine practice differ from patients treated in clinical trials and that almost 60% of mRCC patients in German routine practice would be ineligible for participation in clinical trials. While their first‐line PFS and OS were shorter than those of “trial‐eligible” patients, the PFS and OS of “trial‐eligible” patients were comparable with the results from clinical trials. Physicians should be aware of these differences when discussing treatment options and outcome expectations with patients.

Quality of life assessment in patients with metastatic colorectal cancer receiving maintenance therapy after first-line induction treatment: a preplanned analysis of the phase III AIO KRK 0207 trial.

BACKGROUND First-line maintenance strategies are a current matter of debate in the management of mCRC. Their impact on patients health-related quality of life (HRQOL) has not yet been evaluated. The objective of this study was to assess whether differences in HRQOL during any active maintenance treatment compared with no maintenance treatment exist. PATIENT AND METHODS Eight hundred and thirty-seven patients were enrolled in the AIO KRK 0207 trial. Four hundred and seventy-two underwent randomization (after 24 weeks of induction treatment) into one of the maintenance arms: FP plus Bev (arm A), Bev alone (arm B), or no active treatment (arm C). HRQOL were assessed every 6 weeks during induction and maintenance treatment independent from treatment stop, delay, or modification, and also continued after progression, using the EORTC QLQ-C30, QLQ-CR29. The mean value of the global quality of life dimension (GHS/QoL) of the EORTC QLQ-C30, calculated as the average of all available time points after randomization was considered as pre-specified main endpoint. Additionally, EORTC QLQ-C30 response scores were analyzed. RESULTS For HRQOL analysis, 413 patients were eligible (arm A: 136; arm B: 142, arm C: 135). Compliance rate with the HRQOL questionnaires was 95% at time of randomization and remained high during maintenance (98%, 99%, 97% and 97% at week 6, 12, 18 and 24). No significant differences between treatment arms in the mean GHS/QoL scores were observed at any time point. Also, rates of GHS/QoL score deterioration were similar (20.5%; 17.2% and 20.7% of patients), whereas a score improvement occurred in 36.1%; 43.8% and 42.1% (arms A, B and C). CONCLUSION Continuation of an active maintenance treatment with FP/Bev after induction treatment was neither associated with a detrimental effect on GHS/QoL scores when compared with both, less active treatment with Bev alone or no active treatment. CLINICAL TRIALS NUMBER NCT00973609 (ClinicalTrials.gov).

Routine treatment of patients with chronic lymphocytic leukaemia by office-based haematologists in Germany-data from the Prospective Tumour Registry Lymphatic Neoplasms.

Various treatment options exist for patients with chronic lymphocytic leukaemia (CLL). Clinical registries provide insight into routine treatment and identify changes in treatment over time. The Tumour Registry Lymphatic Neoplasms prospectively collects data on the treatment of patients with lymphoid B‐cell neoplasm as administered by office‐based haematologists in Germany. Data on patient and tumour characteristics, co‐morbidities, systemic treatments, and outcome parameters are recorded. Eight hundred and six patients with CLL were recruited between May 2009 and August 2013. At the start of first‐line treatment, median age was 71 years, 64% were male, and 44% had a Binet stage C disease. The most frequently used first‐line/second‐line regimens were bendamustine + rituximab (BR, 56%/55%), fludarabine + cyclophosphamide + rituximab (FCR, 22%/11%), and bendamustine (B, 5%/9%). Chlorambucil was used in only 7% (first‐line) and 6% (second‐line) of patients. Patients treated with FCR were younger and healthier than patients treated with BR. Overall, 91% of first‐line treatments were successful (40% complete response). Real‐life patient populations differ considerably from patients treated in randomized controlled trials. BR and FCR dominate the first‐line and second‐line treatments of CLL by office‐based haematologists in Germany. Future analysis will investigate progression‐free and overall survival times.

High-Dose Epirubicin in Combination with Cyclophosphamide (HD-EC) in Advanced Breast Cancer: Final Results of a Dose Finding Study and Phase II Trial

In the dose finding study we were able to demonstrate that an increase of the epirubicin dose to 120 mg/m2 in combination with cyclophosphamide (600 mg/m2) is possible. The phase II trial had to check the efficacy and the toxicity of this combination with a therapy interval of 21 days. 34 patients with metastatic breast cancer previously not treated with chemotherapy for metastatic disease entered this phase II trial, which tested the efficacy and toxicity of the chemotherapy combination epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 (HD-EC regimen) i.v. every three weeks. Excluded from the trial were patients at risk of anthracycline toxicity and those with bone or brain metastases. Results compare favourably with best data reported in the literature for chemotherapy of metastatic breast cancer: overall remission rates of 73% (35% CR, 38% PR), median TTP of 58 weeks for CR (range 32-168 weeks) and 52 weeks for the PR group (range 24-110 weeks); median survival time for CR 71+ weeks (range 52-196+), for PR 74+ weeks (range 40-134+ weeks). No therapy was given for remission maintenance after a stable remission was obtained. This results in a very favourable ratio of time with chemotherapy to maintenance time without chemotherapy, which is 10 weeks/62 weeks for CR and 12 weeks/49 weeks for PR. Evidence of tumor remission was found in 80% of the patients who already responded to chemotherapy after the first cycle. The early onset of tumor response as well as the short induction chemotherapy period necessary to obtain best response are considered major advantages of the HD-EC regimen.

Palliative systemic therapy and overall survival of 1,395 patients with advanced breast cancer – Results from the prospective German TMK cohort study

Data on treatment and outcome of advanced breast cancer in routine practice are rare, especially concerning recurrent disease, but important to complement the results from clinical trials and to improve the standard of care. We present data on choice of systemic first-line treatment, number of treatment lines, and survival of patients treated by medical oncologists in Germany. 1395 patients recruited by 124 sites at start of first-line therapy into the ongoing, prospective German clinical cohort study TMK (Tumour Registry Breast Cancer) between February 2007 and October 2015 were analysed. The median OS was 33.8 months (95% CI 30.2-40.2) for HR-positive/HER2-negative, 38.2 months (95% CI 31.3-43.0) for HER2-positive and 16.8 months (95% CI 11.5-22.0) for triple negative breast cancer. Patients with triple negative tumours more often died before start of a third-line therapy than patients with HR-positive or HER2-positive tumours (44% vs. 25%). Use of taxane-based chemotherapies has increased since 2007, with 65% of all first-line chemotherapy-treatments containing taxanes in 2013-15 (60% HR-positive/HER2-negative, 75% HER2-positive, 56% triple negative). 52% of the patients with HR-positive/HER2-negative tumours received first-line endocrine therapy in 2013-15; when restricted to patients with only non-visceral metastases this percentage increased to 63%. To our knowledge, this is the first cohort study showing systemic first-line therapy for all subtypes of advanced breast cancer. Overall survival in the TMK is comparable to that reported by clinical trials despite the inclusion of older and comorbid patients.

Second International Consensus Conference on Advanced Breast Cancer (ABC2), Lisbon, 11/09/2013: The German Perspective.

The Advanced Breast Cancer Second International Consensus Conference (ABC2) on diagnosis and treatment of advanced breast cancer took place in Lisbon, Portugal, on November 7-9, 2013. The focus of the conference was inoperable, locally advanced breast cancer. The diagnosis and treatment of metastatic breast cancer had already been discussed 2 years before at the ABC1 Consensus and were only updated regarding special issues as part of this years ABC2 Consensus. Like 2 years ago, a working group of German breast cancer experts commented on the voting results of the ABC panelists, with special consideration of the German guidelines for the diagnosis and treatment of breast cancer (German Gynecological Oncology Working Group (AGO) recommendations, S3 Guideline) in order to adapt them for daily clinical practice in Germany. The goal of both the ABC Consensus and the German comments is to facilitate evidence-based therapy decisions.

Oxaliplatin-based first-line chemotherapy is associated with improved overall survival compared to first-line treatment with irinotecan- based chemotherapy in patients with metastatic colorectal cancer - results from a prospective cohort study

Purpose Several randomized trials investigating the preferable first-line combination chemotherapy regimen for metastatic colorectal cancer have shown inconsistent findings. Because a substantial number of patients are still being treated with “chemo-only” first-line therapies without targeted agents, we compared overall survival (OS) of patients treated in routine practice with oxaliplatin–fluoropyrimidine and irinotecan–fluoropyrimidine. Patients and methods Using the database of the Tumor Registry Colorectal Cancer, we identified 605 patients with metastatic colorectal cancer who received first-line fluoropyrimidine combination chemotherapy with either oxaliplatin (n=430) or irinotecan (n=175). The Tumor Registry Colorectal Cancer is a cohort study that prospectively documents treatment of colorectal cancer by office-based medical oncologists in Germany and has recruited over 5,000 patients. OS was estimated using the Kaplan–Meier method, and a multivariate Cox proportional hazard model was used to adjust for potentially confounding variables. Results Median OS was 26.8 (95% confidence interval [CI] 22.4–31.9) months with an oxaliplatin–fluoropyrimidine combination and 18.3 (95% CI 15.1–23.2) months with irinotecan–fluoropyrimidine first-line “chemo-only” therapy. Median progression-free survival was 9.0 (8.1–10.2) and 7.9 (7.2–10.2) months, respectively. The difference in OS was confirmed if analysis was restricted to patients with synchronous metastases (no prior treatment). Among other variables, proportion of patients receiving any second-line therapy did not differ between groups. Oxaliplatin-based first-line therapy was associated with improved OS in multivariate analysis adjusted for potentially confounding variables (hazard ratio 0.678, 95% CI 0.510–0.901, P=0.007). Conclusion In clinical routine practice, first-line treatment with oxaliplatin–fluoropyrimidine combination chemotherapy compared to irinotecan–fluoropyrimidine combination is associated with improved survival in patients with metastatic colorectal cancer, independent of all examined potentially confounding factors.

A cross-sectional investigation of fatigue in advanced renal cell carcinoma treatment: Results from the FAMOUS study

OBJECTIVE With an increasing choice of new treatment options, the management of side effects to maintain a chosen treatment if likely to be effective on the tumor remains important. The perception of side effects however varies between the physician and the patient, leading to possible wrong assumptions on tolerability that result in dose modifications, which may ultimately affect effectiveness. The aim was to assess fatigue in patients with advanced or metastatic renal cell carcinoma (RCC) by comparing the evaluation of the physician to the one provided by their respective patient. In addition, we aimed to assess possible influences of fatigue on parameters of quality of life. METHODS Patients receiving systemic treatment for advanced RCC and their physicians were questioned independently regarding incidence and severity of fatigue and its effect on quality of life. RESULTS Both physicians and patients completed 98 matching questionnaires. Patients were treated with sunitinib, sorafenib, bevacizumab combined with interferon alpha, temsirolimus, everolimus, or interferon alpha alone. Incidence and severity of fatigue was differently assessed by patients and physicians, with fatigue being more severe when reported by the patient. The severity of fatigue increased with progressing treatment lines. Quality of life was significantly lower in patients experiencing fatigue compared with patients without fatigue. Emotional, functional, and physical well-being were all affected by fatigue, the latter being the most affected subscale. Social well-being was least affected. CONCLUSION Fatigue is a complex and cumulative condition of patients treated for advanced RCC, and it considerably affects patients quality of life. As many of its underlying causes may be treated, the divergent perception of occurrence and severity of fatigue should be integrated in treatment concepts. The active role of the patient in helping to manage ailments through assessment should be implemented when optimizing treatment of RCC.

Antianemic Treatment of Cancer Patients in German Routine Practice: Data from a Prospective Cohort Study-The Tumor Anemia Registry.

The aim of this prospective cohort study was to assess current antianemic treatment of cancer patients in German routine practice, including diagnostics, treatments, and quality of life (QoL). 88 study sites recruited 1018 patients at the start of antianemic treatment with hemoglobin (Hb) levels <11 g/dL (females) or <12 g/dL (males). Patients were followed up for 12 weeks. 63% of the patients had inoperable solid tumors, 22% operable solid tumors, and 15% hematological malignancies. Over 85% received chemotherapy. Median age was 67 years; 48% were male. Red blood cell transfusions (RBCTx) were given to 59% of all patients and to 55% of the patients with Hb ≥8 g/dL on day 1 of the observation period (day 1 treatment). Erythropoiesis-stimulating agents (ESAs) were the second most frequently applied day 1 treatment (20%), followed by intravenous (IV) iron (15%) and ESA + IV iron (6%). Only about a third of patients were tested for blood serum iron parameters at the start of treatment. Overall, more than half of the patients had long-term responses to antianemic therapy. Our data suggest that in routine practice diagnostics for treatable causes of anemia are underused. A high proportion of cancer patients receive RBCTx. It should be discussed whether thorough diagnostics and earlier intervention could decrease the need for RBCTx. This trial is registered with NCT01795690.