EVITA-a double-blind, vehicle-controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity.

Background: Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab. Patients and methods: Patients receiving first-line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade ≥ 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary end points comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy, and compliance. The study had 80% power to show a 20% reduction of the incidence of grade ≥ 2 skin rash. Results: A total of 126 patients were analyzed. The incidence of skin rash grade ≥ 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anticancer treatment was comparable in both arms. Conclusion: The primary end point of decreasing grade ≥ 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the severity of acne-like skin rash according to WoMo, an alternative and more thorough skin toxicity scoring tool.

Does the Addition of Cetuximab to Radiochemotherapy Improve Outcome of Patients with Locally Advanced Rectal Cancer? Long-Term Results from Phase II Trials.

Purpose. The addition of cetuximab to radiochemotherapy (RCT) failed to improve complete response rates in locally advanced rectal cancer (LARC). We report the long-term results in patients treated within two sequential clinical trials. Methods. Patients receiving neoadjuvant RCT using capecitabine and irinotecan (CapIri) within a phase I/II trial or CapIri + cetuximab within a phase II trial were evaluated for analysis of disease-free survival (DFS) and overall survival (OS). KRAS exon 2 mutational status had been analyzed in patients receiving cetuximab. Results. 37 patients from the CapIri trial and 49 patients from the CapIri-cetuximab treatment group were evaluable. Median follow-up time was 75.2 months. The 5-year DFS rate was 82% (CapIri) and 79% (CapIri-cetuximab) (P = 0.62). The median OS was 127.4 months. 5-year OS was 73% for both groups (CapIri and CapIri-cetuximab) (P = 0.61). No significant difference in DFS (P = 0.86) or OS (P = 0.39) was noticed between patients receiving CapIri and those receiving CapIri-cetuximab with KRAS wild-type tumors. Conclusions. As the addition of cetuximab did not improve neither DFS nor OS it should not play a role in the perioperative treatment of patients with LARC, not even of patients with (K)RAS WT tumors.

Impaired continence function five years after intensified chemoradiation in patients with locally advanced rectal cancer.

AIMS: While the influence on survival is only seen in patients with complete regression after neoadjuvant treatment in locally advanced rectal cancer the impairment of the continence capacity weighs even more for patients with little oncological benefit. METHODS: Patients treated with intensified preoperative radiochemotherapy patients treated only by TME surgery were asked five years after treatment to complete the Wexner and SF-12 quality of life questionnaire. RESULTS: 25 after neoadjuvant treatment had a median Wexner score of 14 [3-20] after 63 [42-78] months. Histopathological stage or grade of regression did not influence the Wexner score (p = 0.76, resp. p = 0.9). 12% describe themselves as being permanently continent; 40% are stool incontinent "always" or "most of the time". 68% are always wearing pads. 29 patients after TME only showed a median Wexner score of 5 [range 0-17] after 66 months [26-133]. SF-12 showed significantly lower values in physical (p = 0.02) as well as mental summary scales (p = 0.015) in patients after RCTX while patients after radical surgery showed no difference to the norm population. CONCLUSION: This study shows that continence is significantly worse five years after neoadjuvant treatment. Moreover, patients after neoadjuvant treatment and surgery have impaired quality of life compared to norm population. These results may contribute to the discussion of only applying neoadjuvant chemoradiation selectively in patients with advanced rectal cancer.

Patients with malignant hematological disorders treated on a palliative care unit: prognostic impact of clinical factors.

A reliable estimation of prognosis in patients receiving palliative care is desirable in order to facilitate clinical decision finding. For patients with advanced hematological malignancies, only few data are available to estimate prognosis of the individual's remaining life span. Here, we sought to investigate potential clinical prognostic parameters in patients with hematological malignancies admitted to a palliative care unit. Using a prospectively collected database, we analyzed clinical and laboratory parameters regarding their prognostic impact in 290 patients with malignant hematological diseases. The parameters included patient-related factors such as Eastern Cooperative Oncology Group (ECOG) performance status, need for transfusions, parenteral nutrition or analgetics, and laboratory values (hemoglobin, platelet count, lactic dehydrogenase (LDH), albumin, total protein, calcium, and C-reactive protein (CRP)) as well as referral symptoms (including anemia, infection, fever, fatigue, and dyspnea). In univariate analyses, LDH (>248 U/l), albumin corrected calcium (>2.55 mmol/l), CRP (>50 mg/l), albumin (<30 g/l), platelet count (<90 × 10(9)/l), total protein (≤60 g/l), hemoglobin (<10 g/dl), opioid treatment, performance status (ECOG >2), and need for parenteral nutrition or blood transfusion significantly correlated with impaired survival. Multivariate analysis showed that low performance status, low platelet count, opioid based pain therapy, high LDH, and low albumin were associated with poor prognosis. Using these five parameters, patients were divided into three "risk groups": low risk (presence of zero to one factor), intermediate risk (two to three factors), and high risk. Median survival for the poor risk patients was 10 days, and the intermediate and low risk patients survived a median of 63 and 440 days, respectively (p < 0.0001). Several clinical and laboratory parameters were associated with a poor prognosis of patients with hematological malignancies treated on a palliative care unit. These parameters might help clinicians to estimate prognosis of remaining life span and individualize treatment and/or end-of-life care options for patients.

Intensified neoadjuvant chemoradiotherapy in locally advanced rectal cancer -- impact on long-term quality of life.

AIMS: In spite of advances in rectal cancer surgery and the use of preoperative 5-fluorouracil-(5-FU) based chemoradiotherapy (CRT) in stage II and III disease distant metastases still occur in about 35-40% of the patients. Intensified preoperative CRT (ICRT) using other drugs in conjunction with 5-FU has been investigated in order to improve the pathological complete remission (pCR) rate and thereby prognosis of patients with locally advanced rectal cancer. However, acute toxicity, especially diarrhea, was reported to be high and no improvement in pCR rates has been observed in randomized trials. Long-term results of these trials are pending. In the present analysis we investigated the impact of ICRT on health related quality of life and long term toxicity. METHODS: The present study included 119 patients with locally advanced rectal cancer who underwent neoadjuvant CRT followed by surgery within controlled clinical trials. Patients received ICRT (n = 83) or standard CRT (n = 36). Evaluation of HRQoL was performed using EORTC QLQ-C30 and QLQ-CR29 questionnaires. RESULTS: The overall rating of global health status/QLQ scale of the EORTC QLQ-C30 questionnaire was identical in both patient groups but patients in the CRT group showed better results in four out of nine function scales. Concerning symptom scales, patients in the CRT arm exhibited significantly less diarrhea (p = 0.028) and less disorders with taste (0.042). CONCLUSIONS: This data suggests that higher gastrointestinal acute toxicity caused by ICRT might lead to a higher risk of long-term deterioration of "gastrointestinal QoL". Future results of randomized trials investigating ICRT versus CRT should be discussed in the light of long-term QoL data.

Capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated tumours: results of an extended phase-I trial.

Preclinical data suggest that the anti-tumour activity of capecitabine is enhanced by taxanes and mitomycin C through up-regulation of thymidine phosphorylase (TP). Here, we studied safety and efficacy of the combination of capecitabine with docetaxel and mitomycin C. Two dose levels (DL) were investigated: capecitabine 1000 mg m(-2) b.i.d. on days 1-14, docetaxel 40 mg m(-2) i.v. day 1, mitomycin C 4 or 6 mg m(-2) i.v. day 1 (DL I or II). Cycles were repeated every 3 weeks. The primary aim was to determine the dose-limiting toxicities (DLT) during the first two treatment cycles and the maximum tolerated dose (MTD). A total of 46 patients (pts) refractory to standard therapies were enrolled, of whom the majority had gastrointestinal tumours (n=40). 14 pts had received >/=3 lines of prior chemotherapy. At DL I, one out of six pts experienced DLT. At DL II, two out of six pts had DLT (mucositis grade 3). Thus, DL I was determined as MTD. Among a total of 37 pts treated on DL I the following toxicities were observed during cycles 1 and 2 (number of patients with grade 1/2/3/4 toxicity; NCI-CTC v. 3.0): anaemia 10/8/3/0, leucocytopenia 4/11/1/2, thrombocytopenia 0/1/2/0, diarrhoea 8/1/2/0, stomatitis/mucositis 3/3/1/0, nausea/vomiting 10/2/0/0, and hand-foot skin reaction 5/1/1/0. Of 30 pts who received at least two treatment cycles nine achieved complete or partial remissions, six pts achieved minor remissions, and seven pts had stable disease (tumour control rate 73%). Of note, four out of 10 patients with pancreatic cancer had partial remissions. In conclusion, capecitabine can safely be combined with docetaxel (40 mg m(-2)) and mitomycin C (4 mg m(-2)). The established regimen was well tolerated and the preliminary efficacy data in this heavily pre-treated patients population appears to be promising.

Integrating emergency services in an urban health system.

When planning for growth and management efficiency across urban health systems, economic and market factors present significant service line challenges and opportunities. This article describes the evolutionary integration of emergency services in St John Health System, a large, religious-sponsored health care system located in Detroit, Michigan. Critical business elements, including the System's vision, mission, and economic context, are defined as the framework for site-specific and System-wide planning. The impact of managed care and market changes prompted St John's clinicians and executives to explore how integrating emergency services could create a competitive market advantage.