Effects of zoledronic acid on proteinase plasma levels in patients with bone metastases.

Background: The effects of the bisphosphonate derivative zoledronic acid (ZA) on the > circulating levels of matrix metalloproteinase-2 (MMP-2), matrix metallo-proteinases-9 > (MMP-9), cathepsin B (Cath B) and urokinase-type plasminogen activator (uPA) in > patients with bone metastasis (BMTS) and the possible correlation with the symptomatic > response induced by this drug in these patients were evaluated. Patients and Methods: > Proteinase levels were determined by enzyme-linked immunosorbent assay (ELISA) in the > plasma of 30 patients with painful bone metastases from breast or prostate cancer > undergoing multiple treatment with ZA (4 mg i.v., every 4 weeks). Healthy subjects > (HS) of both genders (12 female and 30 male) served as the control group. The > symptomatic response to ZA was assessed by the visual analog scale score (VAS). > Results: The median MMP-2 and MMP-9 pretreatment levels were more elevated in BMTS as > compared to HS (p¡Ü0.0001). Conversely, uPA levels were lower in BMTS p=0.0033; no > significant difference was observed for Cath B. ZA administration was associated with > a symptomatic response (VAS score¡Ü4) in 25/30 patients (83.3%) (p<0.0001). This > phenomenon paralleled a decrease of Cath B and MMP-2 plasma concentrations from > baseline values on week 12 (p=0.05). A similar trend, although not statistically > significant, was also noted for MMP-9 and uPA. However, no direct relationship was > observed between the analgesic effect induced by ZA and changes in the circulating > levels of these enzymes. Conclusion: These data show that ZA administration may > provide relief from bone pain in patients with diffuse skeletal metastases and confirm > a possible implication of cysteine proteinases and matrix metalloproteinases in bone > metastasis formation, but not in the pathogenesis of metastatic bone pain

MMP-2, MMP-9 and activin A blood levels in patients with breast cancer or prostate cancer metastatic to the bone.

Background: The clinical significance of the circulating levels of activin A and matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) was investigated in patients with breast cancer (BC) or prostate cancer (PC) with (M1) or without (M0) bone metastasis. Patients and Methods: MMP-2, MMP-9 and activin A blood concentrations were measured by enzyme immunoassays in 79 cancer patients and in 57 healthy blood donors (HS) who served as a control group. The diagnostic accuracy of these molecules to discriminate between M0 and M1 patients was evaluated by the receiver operating characteristic curve (ROC) and compared to that of tumor markers CA15.3 or prostate-specific antigen (PSA). Results: Activin A and MMP-2 were significantly increased in BC and PC patients as compared to sex-matched HS while MMP-9 levels were more elevated only in the PC patients. Interestingly, in the PC patients, activin A levels were significantly higher than those measured in the BC patients. In this latter group, activin A and CA15.3 but not MMP-2 or MMP-9 were increased in the M1 patients as compared to M0 patients. Furthermore, a significant relationship was also highlighted between activin A concentration and the number of bone metastases and tumor grade, between MMP-9 and tumor grade, and between MMP-2 and CA15.3. ROC curve analysis showed a good diagnostic accuracy for activin A and CA15.3 but a poor accuracy for MMP-2 and MMP-9 in discriminating between M0 and M1 patients. However, CA15.3 retained the best diagnostic accuracy in this respect. In the PC group, only activin A and PSA levels were significantly increased in the M1 patients as compared to the M0 patients. A similar although not statistically significant trend was noted for MMP-9. Interestingly, a significant correlation was observed between PSA and activin A and MMP-9, and between Activin A and Gleason score and the number of skeletal metastases. ROC curve analysis showed a good diagnostic accuracy for activin A, MMP-9 and PSA and a poor diagnostic accuracy for MMP-2 in detecting M1 patients. However, PSA showed the highest diagnostic accuracy. Conclusion: Activin A, MMP-2 and MMP-9 may be regarded as possible therapeutic targets in the treatment of metastatic bone disease. However, their usefulness as additional markers of bone metastasis remains to be better define

A case of guillain-barre syndrome in a patient with non small cell lung cancer treated with chemotherapy

Guillain-Barré Syndrome (GBS) is a demyelinating polyneuropathy of probable autoimmune pathogenesis characterized by rapidly progressive symmetric paralysis. In the literature some cases of GBS associated with anticancer chemotherapy are reported. We present a case of a 55-year old woman who complained of progressive motor deficit in four limbs, areflexia in lower limbs and facial nerve paralysis one week after beginning cisplatin-gemcitabine chemotherapy for metastatic lung cancer. The cerebrospinal fluid analysis showed a strong positive Pandy reaction with 435 mg/dl total protein. The electromyography and the electroneuronography established the diagnosis of inflammatory demyelinating polyneuropathy. Specific therapy with intravenous immunoglobulin 25 g/day in 5 administrations for 5 days was started with complete benefit

Managing cancer patients with acute venous thromboembolism: exploring safe alternatives to hospitalisation

Acute venous thromboembolism (VTE) is a common and potentially fatal complication that frequently occurs in cancer patients. Few data are currently available about the optimal management of this category of high-risk patients. In clinical practice, physicians have to deal with many problems related to cancer patients with acute VTE. For instance, cancer patients with deep vein thrombosis (DVT) are frequently admitted to the hospital since their high rate of recurrent thrombotic events and/or bleeding-related therapy; however, most of them would prefer alternatives to prolonged hospitalisation. Then, it is not clearly whether data coming from a non-cancer population (such as that regarding the use of D-dimer test and/or pre-test clinical probability [PCP]), can be reliable applied in cancer patients. Finally, scanty information is present on the feasibility of the "home-treatment program" for DVT in this category of high-risk patients. In our review we present data on a population of cancer patients evaluated at the Emergency Care in whom we have evaluated: 1) the diagnostic accuracy of PCP and D-dimer test; 2) the safety and efficacy of low molecular weight heparins (LMWH) as "protective anticoagulation" in case of deferred imaging for VTE and 3) the safety and efficacy of home treatment