Optimal tolerability and high efficacy of a modified schedule of lapatinib-capecitabine in advanced breast cancer patients.

PURPOSE: Diarrhea in relation to the lapatinib-capecitabine regimen is a common and debilitating side effect which may interfere with optimal treatment delivery. We performed a post hoc analysis in human epidermal growth factor receptor 2-positive advanced breast cancer patients treated with a modified schedule in its administration, aimed primarily to evaluate grade (G) ≥ 2 diarrhea incidence and, secondarily, treatment efficacy. PATIENTS AND METHODS: Treatment schedule consisted of lapatinib 1,250 mg daily for the first 10 days, then in combination with capecitabine, 2,000 mg/m(2), starting day 11 for the first cycle, and thereafter from day 8, for 14 days of a 21-day cycle, in 3 daily administrations. Lapatinib was dissolved in water, and cholestyramine was continuously given twice a day. RESULTS: Among 38 patients treated and analyzed, the incidence of G ≥ 2 diarrhea was 13.2 %. In 28 patients diarrhea was not observed, while G1-2 diarrhea was reported in 9 (23.7 %) patients; a single episode of G3 diarrhea was observed in 1 (2.6 %) patient. Overall response rate was 34.2 %, clinical benefit 55.3 %, and median progression-free survival 10 months. CONCLUSION: The results of the present post hoc analysis are very encouraging, both in terms of tolerability and treatment efficacy, and all data compare favorably with previous reports of "conventional" administration of the lapatinib-capecitabine regimen.

High serum levels of TNF-α and IL-6 predict the clinical outcome of treatment with human recombinant erythropoietin in anaemic cancer patients.

BACKGROUND: A number of anaemic cancer patients are not responsive to treatment with recombinant human erythropoietin (rHuEPO). The aim of the present study is to investigate whether serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and additional laboratory parameters, together with clinical variables, can predict the clinical outcome of treatment with rHuEPO in anaemic cancer patients. PATIENTS AND METHODS: Thirty-five cancer patients and 25 healthy controls were enrolled in this study. Patients were treated with epoetin alfa at the dose of 150 IU/kg s.c. three times a week for 12 weeks. If the haemoglobin (Hb) level failed to improve at least 2 g/dl above baseline by week 6 of treatment, dose was increased to 300 IU/kg s.c. for the remainder of the treatment period. All patients filled out the Brief Fatigue Inventory (BFI), a questionnaire for the self-evaluation of cancer-related fatigue. Serum samples from patients and control groups were frozen at -80 degrees C and TNF-alpha, IL-1beta and IL-6 were later examined by enzyme-linked immunosorbent assay. RESULTS: Fatigued cancer patients had significant higher levels of circulating TNF-alpha, IL-1beta and IL-6 than healthy controls. Responders (Rs) to erythropoietin had significant lower medium levels of TNF-alpha and IL-6 than nonresponders (NRs). Fatigued patients with a general BFI score > or =6 presented higher medium level of cytokines than nonfatigued patients (general BFI score <6), but each group responded similarly to treatment with rHuEPO. CONCLUSIONS: High serum levels of TNF-alpha and IL-6 at the baseline are significantly correlated with a negative response to administration with rHuEPO. Thus, pretreatment evaluation of TNF-alpha and IL-6 serum levels can help to select those patients who are most likely to benefit from treatment with rHuEPO. On the contrary, Hb level, red blood cell count, lactate dehydrogenase and BFI score do not predict the outcome of treatment with rHuEPO.

Neuroimmunomodulation and psychoneuroendocrinology: recent findings in adults and aged.

In recent years the relationships among immune, endocrine and nervous systems have been extensively studied, and grouped in a new research field: psychoneuro-immunoendocrinology. Since ancient times its has been known that, in humans, mood as well as environmental influences could affect health. In the late '70s, only, evidence of bi-directional pathways has been achieved, first in animal models and, later on, in humans. We reviewed current knowledge on neuroimmunomodulation, concerning the influence of stress and psychological status on immunity as well as neuroendocrine modulation by the immune system, reporting some data obtained from our studies. Particularly, having detected a relevant impairment concerning most of the parameters studied, we emphasized the effects of depressive disorders on immune function in the elderly.

Effects of VM-26 and lonidamine on a B16 melanoma cell line.

The treatment of exponentially-growing B16 melanoma cells with teniposide causes a dose- and time-dependent decrease of cell survival. By means of the nucleoid technique, the formation of double strand breaks was demonstrated in the nuclei of the treated cells, indicating a possible involvement of topoisomerase II. DNA double strand breaks were rapidly but ineffectively repaired. Morphometric and densitometric analyses showed that teniposide treatment causes a considerable increase of nuclear area, nuclear DNA and cell size, associated with a lowering of the mitotic index to less than one hundredth of that of the controls. The cytocidal effect of VM-26 can be potentiated by the addition of a non-lethal dose of lonidamine, whose synergism is particularly evident at low teniposide concentrations.

Serum IgE and atopy in drug-sensitive patients.

One of the most interesting aspects of the pathogenesis of the allergic and pseudo-allergic reactions to drugs is the one concerning the possible roles of genetic factors, in general, and the relationship with atopy, in particular. We decided to study the correlation between the serum level of total IgE, the personal and familial history of atopy, and the allergologic tests (skin test, PRIST, RAST, etc) for one or more drugs taken by 465 patients with personal history of allergic reactions. From the data, we observed that the average amount of total IgE lies within the norm, 125.4 KU/L (+/- 209.2), without any significant difference between the allergic (132 KU/L) and the pseudo-allergic (121.8 KU/L) patients. The IgE levels tend to be higher in that part of the tested population which presented a circumstantial atopic status (11.8%) and they are not influenced by an allergic or pseudo-allergic reaction to drugs. According to these results, the relationship between drug hypersensitivity and atopy needs further investigation.

Depression of direct plaque-forming cell response in mouse spleen cell cultures by aggregated IgG2b-induced factors.

Mouse spleen cells were treated with concanavalin A (Con A) or aggregated mouse IgG2b for 48 h in culture. When cells thus treated were added to fresh mouse spleen cell cultures immunized with SRBC they depressed the response of B lymphocytes as measured by enumerating plaque forming cells (PFC) on the fourth day of culture. When supernatant from cells cultured with IgG2b was added to immunized cultures this resulted in depression of PFC generation similar to that observed by addition of treated cells. The depression observed was essentially in the same range as that observed by addition of Con A treated cells or their supernatant. These observations extend previous work suggesting that IgG2b-induced PFC depression may result from activation of suppressor T cells with elaboration of soluble suppressor factors. This mechanism of immunomodulation may be important in the pathogenesis of immune complex disorders.