Occupational exposure to cytostatic fumes during hyperthermic intraperitoneal chemotherapy.

Hyperthermic intraperitoneal chemotherapy (HIPEC)-heated, intra-abdominal chemotherapy-has become the treatment of choice for treating peritoneal metastases from ovarian, stomach or colorectal cancers. HIPEC has several advantages and disadvantages. The major benefit is minimal systemic toxicity for the patient, but there is a risk of occupational exposure for operating room staff. We have not found any reports of workers with chronic aplastic anaemia as a result of exposure to cytostatic fumes during HIPEC. The aim of this case report is to raise the awareness of potential negative health effects of inhalation exposure to cytostatic drugs. We present a rare case of a 43-year-old woman, suffering from aplastic anaemia as a long-term consequence of exposure to cytostatics. During the HIPEC procedure, surgical revision of the peritoneal cavity was undertaken which resulted in release of cytostatic fumes. Despite awareness of the health effects of occupational exposure to cytostatic drugs and well-developed procedures for safely handling them, unexpected exposure may occur causing serious medical conditions. These may develop in sensitive subjects although accidental high-level exposure may lead to unexpected long-term consequences in all workers. Medical staff need to be informed of the risks of HIPEC and safety guidelines to reduce the risk of exposure.

Magnetic field therapy in patients with cytostatics-induced polyneuropathy: A prospective randomized placebo-controlled phase-III study.

No causal treatment for chemotherapy-induced peripheral neuropathy (CIPN) is known. Therefore, there is an urgent need to develop a therapy for CIPN. Only scarce clinical data are available concerning magnetic field therapy (MFT) in this context. We conducted a unicentric, randomized, double-blind, placebo-controlled phase-III trial of an MFT device versus placebo. In this study, we randomized 44 patients with CIPN to two treatment groups, where 21 patients were treated with MFT (Group 1) and 23 patients received placebo (Group 2). We evaluated the efficacy of MFT at baseline (T1 ), after 3 weeks of study treatment (T2 ), and after 3 months of study treatment (T3 ). The primary endpoint was nerve conduction velocity (NCV), while secondary endpoints were the Common Toxicity Criteria (CTCAE) score and the Pain Detect End Score at T3 . Seventeen of the patients in Group 1 and 14 patients in Group 2 completed the respective study treatment. The primary endpoint, significant improvement of NCV at T3 , was achieved by MFT (P = 0.015), particularly for sensory neurotoxicity of the peroneal nerve. Also, in respect to the secondary endpoints, significant improvement (P = 0.04) was achieved in terms of the patients' subjectively perceived neurotoxicity (CTCAE score), but not of neuropathic pain (P = 0.11). From data in the randomized study presented here, a positive effect on the reduction of neurotoxicity can be assumed for the MFT device. Patients with sensory neurotoxicity in the lower limbs, especially, should therefore be offered this therapy. Bioelectromagnetics. 38:85-94, 2017. © 2016 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.

Bilberry extract, its major polyphenolic compounds, and the soy isoflavone genistein antagonize the cytostatic drug erlotinib in human epithelial cells.

Erlotinib (Tarceva®) is a chemotherapeutic drug approved for the treatment of pancreatic cancer and non-small cell lung cancer. Its primary mode of action is the inhibition of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK). Recently, RTK-inhibiting polyphenols have been reported to interact synergistically with erlotinib. Furthermore some anthocyanidins and anthocyanin-rich berry extracts have been reported to inhibit tyrosine kinases, including the EGFR, which raises the question of potential interactions with erlotinib. Polyphenol-rich preparations such as berry- or soy-based products are commercially available as food supplements. In the present study we tested a bilberry extract, its major anthocyanin and potential intestinal degradation products, as well as genistein, with respect to possible interactions with erlotinib. Cell growth inhibition was assessed using the sulforhodamine B assay, while interactions with EGFR phosphorylation were analyzed by SDS-PAGE/western blotting with subsequent immunodetection. Genistein, bilberry extract, delphinidin-3-O-glucoside and delphinidin were found to antagonize erlotinib whereas phloroglucinol aldehyde was found to enhance cytostatic effects of the drug on human epithelial A431 cells. Genistein also antagonized the EGFR inhibitory effects of erlotinib, whereas bilberry anthocyanins showed no significant interactions in this regard. Our data indicate that different polyphenols are potentially able to impair the cytostatic effect of erlotinib in vitro. Genistein interacts via the modulation of erlotinib-mediated EGFR inhibition whereas bilberry anthocyanins modulated the growth-inhibitory effect of erlotinib without affecting EGFR phosphorylation, thus indicating a different mechanism of interference.

Low frequency magnetic field therapy in patients with cytostatic-induced polyneuropathy: a phase II pilot study.

Cytostatic-induced polyneuropathy (CIPN) is a common and serious toxicity in tumor patients. Treatment and prophylactic measures are mainly ineffective. Therefore, there is an urgent need to establish a sufficient therapy for pPNP. Between July 2007 and August 2008, 20 patients were treated with low frequency (4-12 Hz) magnetic field therapy (MFT), and neurological examinations were conducted at the trial therapy's beginning, as well as after 3-4 weeks. Standardized testing methods were applied, i.e., the Common Toxicity Criteria questionnaire of the National Cancer Institute and the measurement of nerve conduction velocity (NCV) in the electrophysiological examination. In terms of the components sensory ataxia and neuropathy as well as neuropathic pain, an improvement was achieved using MFT. This effect was confirmed by an increase in NCV. Using low frequency MFT, CIPN was influenced positively on both hands and feet. This could represent a future therapy principle for these patients.