[Effects of a Phone-Based Follow-Up Care After Inpatient Rehabilitation for Breast Cancer Patients - A Randomized Controlled Trial]. / Effekte der telefonischen Nachsorge in der onkologischen Rehabilitation nach Brustkrebs ­ Ergebnisse einer randomisierten Studie.

Background Benefit and long-term effects of rehabilitation and psychoeducational interventions after cancer therapy are still controversial discussed. Aim of the study was to evaluate feasibility and effects of a telephone-based follow-up intervention after oncological rehabilitation. Methods 172 breast cancer patients (age 27-54 years) were randomized after inpatient rehabilitation to a telephone-based intervention (phone calls every 4 weeks over 6 months) or control group. Patients were evaluated by standardized questionnaire (e. g. IRES-24, HADS, LZI, emotional thermometer, questionnaire "return to work") at T1 (start of rehabilitation), T2 (end of rehabilitation) and T3 (6 months after rehabilitation). Results 2-way-ANOVAs were performed to evaluate long-term effects. Main effects of IRES-24 and HADS were significant depending on time (IRES-24 F(2,116)=40.49, p<0.01 and HADS F(2,117)=31.50, p<0.01; (F(2,11 6)=31.19, p<0.01) but no significant differences between the intervention and control group were seen. Conclusions Telephone-based follow-up care is feasible with high patient acceptance. However an improvement of therapeutic effects in the intervention group were not be detected by IRES-24 and HADS questionnaire. Potential explanations may be the low "dosage" (duration/quantity of phone calls) of the intervention or the fact that in the last years multimodal treatment interventions were established in German rehabilitation centers leading to a so-called "ceiling effect" without significant effects of additional follow-up interventions.

Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: an analysis of the AIO KRK-0104 trial.

PURPOSE: AIO KRK-0104 investigated first-line therapy of metastatic colorectal cancer (mCRC) with cetuximab, capecitabine and irinotecan versus cetuximab, capecitabine and oxaliplatin. This analysis investigated the impact of primary tumor location on outcome of patients. PATIENTS AND METHODS: Left-sided primary tumors were defined as tumors from rectum to left flexure, while tumors in the remaining colon were regarded right sided. Overall survival (OS), progression-free survival (PFS) and response rate were correlated with primary tumor location. A Cox regression model was used to evaluate interaction between primary tumor location and KRAS mutation. RESULTS: Of 146 patients of the AIO KRK-0104 trial, 100 patients presented left-sided (of those 68 KRAS codon 12/13 wild-type) and 46 patients right-sided primary tumors (of those 27 KRAS codon 12/13 wild-type). Left-sided tumors were associated with significantly longer OS (p = 0.016, HR = 0.63) and PFS (p = 0.02, HR = 0.67) as compared to right-sided tumors. These effects were present in the KRAS codon 12/13 wild-type population (HR OS: 0.42; HR PFS: 0.54), while no impact of primary tumor location was evident in patients with KRAS codon 12/13 mutant tumors (HR OS: 1.3; HR PFS: 1.01). A significant interaction of KRAS status and primary tumor location concerning OS and PFS was observed. CONCLUSION: Our findings suggest that primary tumor location and KRAS codon 12/13 mutational status interact on the outcome of patients with mCRC receiving cetuximab-based first-line therapy. Left-sided primary tumor location might be a predictor of cetuximab efficacy.

Correlation of capecitabine-induced skin toxicity with treatment efficacy in patients with metastatic colorectal cancer: results from the German AIO KRK-0104 trial.

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.

Long-term treatment of advanced hepatocellular carcinoma with the tyrosine kinase inhibitor erlotinib (Tarceva)--a case report.

AIM: Hepatocellular carcinoma (HCC) is the 5th most common human malignancy with an increasing incidence in western countries and still unsatisfactory median survival rates of 5 - 7 months. Currently, new treatments with biologicals (so-called "targed therapies") such as VEGF and EGF antibodies or tyrosine kinase inhibitors (e. g., sorafenib) are being tested in patients with HCC. Here we report a long-term treatment of an advanced, multifocal HCC with the tyrosine kinase inhibitor erlotinib (Tarceva). PATIENT AND METHODS: A 64-year-old man with newly diagnosed and histologically proven advanced HCC and hydropic liver cirrhosis (Child-Pugh B) was treated for 18 months (12 / 05 - 06 / 07) with erlotinib. In addition paracentesis was performed every 6 weeks to provide relief from ascites. RESULTS: After 2 weeks of treatment with 100 mg erlotinib QD the patient developed a 3 degrees-4 degrees skin toxicity (haemorrhagic rush). Other major side effects did not occur. Erlotinib medication was stopped for 2 weeks and re-started at a reduced dose of 75 mg QD. Marker tumour lesions (No. 1: caudate lobe/No. 2: segment III), liver enzymes and synthesis parameters (albumin, prothrombin time/INR) and frequency of paracentesis remained stable during the 18 months of observation. CONCLUSIONS: Erlotinib (Tarceva) appears to be an interesting treatment option for patients with advanced HCC. More clinical data and studies are needed to confirm this result.

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial.

This prospective multicentre phase II study characterises the toxicity and activity of first-line capecitabine and oxaliplatin combination therapy (CAPOX) in advanced biliary system adenocarcinomas. Patients received oxaliplatin (130 mg m(-2), day 1) plus capecitabine (1000 mg m(-2) b.i.d., days 1-14) every 3 weeks. Patients were stratified prospectively into two groups based on location of the primary (gallbladder carcinoma (GBC) or extrahepatic cholangiocarcinoma (ECC) versus intrahepatic mass-forming type cholangiocarcinoma (ICC)). Sixty-five patients were evaluable. The response rate in 47 patients with GBC/ECC was 27% (4% complete responses), and in 23 patients (49%) stable disease (SD) was encountered. In 18 patients with ICC, we observed no objective responses, but 6 patients (33%) had SD. Median survival was 12.8 months (95% CI, 10.0-15.6) for patients with GBC or ECC (GBC: 8.2 months; 95% CI, 4.3-11.7; ECC: 16.8 months; 95% CI, 12.7-20.5), and 5.2 months (95% CI, 0.6-9.8) for ICC patients. In both cohorts, therapy was well tolerated. The most common grade 3-4 toxicity was peripheral sensory neuropathy (11 patients). Our data suggest that the CAPOX regimen is a well-tolerated and active treatment option for advanced ECC and GBC but might produce poorer results for ICC.

Studies on p53, BAX and Bcl-2 protein expression and microsatellite instability in stage III (UICC) colon cancer treated by adjuvant chemotherapy: major prognostic impact of proapoptotic BAX.

We evaluated the expression patterns of proapoptotic BAX, antiapoptotic Bcl-2 and p53, the proposed upstream effector of these molecules, as potential prognostic markers in UICC stage III colon cancer by immunohistochemical staining. To identify high-frequency microsatellite instability (MSI+) individuals, we performed single-strand conformation polymorphism-based analysis for BAT26. A total of 188 patients who had received 5-fluorouracil (5-FU)-based adjuvant chemotherapy (5-FU/folinic acid or 5-FU/levamisole) were enrolled. Median follow-up was 84.5 months. We found that BAX, Bcl-2 and p53 protein expressions were high or positive in 59, 70 and 50% of 188 cases, respectively. MSI+ tumours were detected in 9% of 174 evaluable patients. BAX or Bcl-2 was correlated with a higher degree of differentiation or left-sided tumours (P=0.01 or P=0.03, respectively); MSI was correlated with right-sided tumours (P<0.0001). In contrast to p53, Bcl-2, or MSI, low BAX, advanced pN category, low grade of differentiation and treatment with 5-FU/levamisole were univariately associated with poorer disease-free survival (DFS) (P=0.0005, P=0.001, P=0.005 and P=0.01, respectively) and poorer overall survival (OS) (P=0.002, P=0.0001, P=0.003 and P=0.02, respectively). Besides pN category and treatment arm, BAX was an independent variable related to both OS and DFS (P=0.003 and P=0.001, respectively). In both univariate and multivariate analysis, the p53-/BAX high in comparison with the p53+/BAX high subset conferred a significantly improved DFS (P=0.03 and P=0.03, respectively) as well as a marginally improved OS (P=0.07 and P=0.08, respectively). BAX protein expression may be of central significance for clinical outcome to 5-FU-based adjuvant chemotherapy in stage III colon cancer, and bivariate analysis of p53/BAX possibly may provide further prognostic evidence.

[A 56-year-old female patient with Raynaud's syndrome, increased liver enzymes and neuropsychiatric symptoms]. / 56-jährige Patientin mit Raynaud-Symptomatik, erhöhten Leberenzymen und neuropsychiatrischen Symptomen.

CASE HISTORY: A 56-year-old woman presented with increased liver enzymes (GPT, GOT), arthralgias, Raynaud's syndrome and disturbance of sleep and concentration. FINDINGS AND DIAGNOSIS: Serology and liver biopsy indicated chronic hepatitis C infection (HCV) and viral-induced liver cirrhosis with unremarkable liver synthesizing parameters. An HCV-triggered cryoglobinemia was excluded, but high elevated antinuclear antibodies (ANA) and anti-RNP autoantibodies, typical serological parameters of mixed tissue collagenous (Sharp}s disease), were detectable. Magnetic resonance spectroscopy (H-MRS) was performed to differentiate between cerebral vasculitis and mild hepatic encephalopathy. This detected abnormal pattern of cerebral metabolites (myo-inositol and choline), is specific for HE. TREATMENT AND COURSE: After onset of an antiviral therapy (terferon/ribavirin), low protein diet with supplementation of l-ornithine-l-aspartate the arthralgia and neuropsychiatric symptoms rapidly improved and HCV-RNA PCR became negative. Unfortunately, after cessation of antiviral treatment the patient had a relapse of HCV with a worsening of the arthralgia and the Raynaud symptoms (HCV-triggered Sharp}s disease). CONCLUSION: Even in patients with mildly abnormal liver function and liver cirrhosis it is important to consider (mild) hepatic encephalopathy if neuropsychiatric symptoms occur.

[Detection of subclinical and overt hepatic encephalopathy and treatment control after L-ornithine-L-aspartate medication by magnetic resonance spectroscopy ((1)H-MRS)]. / Detektion und Therapieverlaufskontrolle der subklinischen und manifesten hepatischen Enzephalopathie nach Behandlung mittels L-Ornithin-L-Aspartat durch Protonen-Magnetresonanzspektroskopie ((1)H-MRS).

Hepatic encephalopathy (HE) is a common problem in liver cirrhosis and is associated with typical changes of cerebral metabolite pattern observed by proton magnetic resonance spectroscopy (MRS). In HE, a reduction of the cerebral myo-inositol (mI) and choline (Cho) and an increase of glutamine/glutamate (Glx) can typically be detected with this method. In the present study MRS was used to assess prospectively specific parameters of cerebral metabolism before and after 6 days of treatment with a low-protein diet and with L-ornithine-L-aspartate (LOLA). 6 patients with liver cirrhosis were included in this pilot study. According to standardized neuropsychological tests overt HE or subclinical HE was detected in all patients. All patients received a low-protein diet (< 60 g/d) and were treated additionally with LOLA (20 g QD i. v.). MRS examinations were done before and after 6 days of treatment and the results were compared with those of healthy volunteers. Before treatment mI/Cr ratios in the grey matter were reduced significantly in cirrhotic patients as compared to healthy volunteers (0.30 +/- 0.22 vs. 0.68 +/- 0.11; P = 0.028). In addition, patients showed a (non-significant) reduction of the Cho/Cr-ratio (0.19 +/- 0.03 vs. 0.25 +/- 0.02; P = 0.17) and an elevated Glx/Cr-ratio (1.84 +/- 0.63 vs. 1.29 +/- 0.31; P = 0.05). After 6 days of treatment a significant increase of the Cho/Cr ratio (0.23 +/- 0.03 vs. 0.19 +/- 0.03; P = 0.028) was detectable and 5 of the 6 patients showed a (not significant) decrease of the elevated Glx/Cr ratios. After cessation of treatment an improvement in neuropsychological tests as shown by number-connection testing (P = 0.046) as well as a decrease of elevated pre-treatment ammonia blood levels were noted. These findings, however, did not correlate with the Child-Pugh classification or evidence of clinical/subclinical HE. Using (1)H-MRS it is possible to observe a specific pattern of cerebral metabolites in patients with overt and subclinical HE. In this pilot study a fast change of cerebral metabolite pattern after specific therapy of HE with LOLA was detected. Therefore, future studies with larger patient groups are needed to establish (1)H-MRS as an objective method for detection and treatment control in overt and subclinical HE, especially when compared to commonly used parameters such as ammonia levels or standardized neuropsychological tests.

Oxaliplatin, fluorouracil and leucovorin for advanced biliary system adenocarcinomas: a prospective phase II trial.

We studied the activity of combined oxaliplatin and fluorouracil-leucovorin in 16 consecutive patients with advanced biliary tract adenocarcinomas. The disease control rate (responses and stable disease) was 56% (95% confidence interval, 29-84%) and the median overall survival time was 9.5 months (range 0.9-26.8+). Therefore, this regimen might be active in biliary adenocarcinomas with further evaluation necessary.