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Background: Platinum resistance constitutes a therapeutic challenge in the treatment of ovarian cancer, with overall unsatisfactory response rates to standard chemotherapy and correspondingly low survival. Regional abdominal hyperthermia and bevacizumab are treatment options that have both shown the capacity to improve the results of standard chemotherapy in the platinum-resistant situation, when added to the treatment schedule., Case Report: We report on a 29-year-old patient with primary platinum-refractory ovarian cancer, who was treated with a combination of pegylated liposomal doxorubicin, regional abdominal hyperthermia and bevacizumab in a four-week cycle over a long-term period of 38 months. Due to an excellent clinical and radiologic response resulting in stable disease, with a concomitant mild toxicity profile consisting only of intermitted diarrhoea and mild fatigue [corrected] , the treatment was continued in an ambulatory setting., Discussion: To our knowledge we describe the first experience with combination treatment of pegylated liposomal doxorubicin with regional abdominal hyperthermia and bevacizumab in a long term setting of almost 2 years. Excellent response with comparably low toxicity was demonstrated. Further evaluation as a therapeutic option in this heavily pretreated and highly palliative patient population is warranted.

We studied, in vitro, the stimulating effects of a commercial preparation of low molecular thymic peptides (TP) on the immunocytotoxicity of peripheral blood lymphocytes and monocytes from patients with breast tumors, melanoma and colorectal tumors. On average, tumor patients showed a lower natural killer (NK), lymphokine (IL-2) activated killer (LAK) cell and basic tumoristatic activity of monocytes, compared with healthy donors. There was no correlation between the NK-cell number and the NK-cell activity of the tumor patients. The TP showed no effects on the NK-cell activity in any group, yet elevated the deficient LAK-cell activity of tumor patients and that of healthy donors. On monocytes, TP enhanced the deranged tumoristatic activity only in tumor patients, while being slightly inhibitory on control monocytes. Dividing the donors on the basis of the TP effects on cytotoxicity of the mononuclear cells into TP-nonresponders and TP-responders, a higher number of TP-responders was found among tumor patients, compared with healthy donors. Moreover, a higher number of TP-nonresponders were observed with lymphocytes from colorectal tumor patients at advanced tumor stage. Therefore, on the basis of the applied immunocytotoxic assays, these results may provide a basis for selecting tumor patients, who may respond to TP in immunotherapy protocols.

The effects of a thymic peptide preparation (TP) on the immunocytotoxicity and cytokine secretion of peripheral blood lymphocytes and monocytes from patients with colorectal tumors, breast tumors and melanoma were studied in vitro. On average, breast tumor and melanoma patients showed significantly lower natural killer (NK) cell activities than colorectal tumor patients and normal controls. In contrast, the generation of lymphokine (IL-2) activated killer (LAK) cells was found to be comparable within the different tumor diseases (24% cytotoxicity), but lower than in the group of normal controls. TP, being without any effects on NK cell activity in all groups, increased the deficient LAK cell activity of breast tumor and melanoma patients, as well as of normal controls? without significant effects on PBL from colorectal tumor patients. This increase was found to be associated with an increase of the IL-2 induced IFN-gamma and, on a lower level, TNF-alpha secretion, especially from breast tumor and melanoma patients. In addition, monocytes from these patients showed a deranged tumoristatic activity, compared to colorectal tumor patients and normal controls. The stimulation of monocytes by IFN-gamma greatly elevated the mean of the antitumor activity in all groups studied. TP being slightly effective on monocytes from melanoma patients, did not further enhance monocyte-mediated cytotoxicity when applied alone or in combination with IFN-gamma. Reduced basal monocytic chemokine levels were only found in the groups of melanoma (IL-8) and colorectal tumor patients (MCP-1), whereas RANTES secretion was increased, compared to normal controls. TP was active only in reducing the IL-8 secretion of monocytes from colon tumor patients. The results indicate that selected functions of peripheral blood mononuclear cells can be partially improved by the thymic peptide preparation.