Introduction of a new semi-quantitative index with predictive implications in patients with painful osseous metastases after (186)Re-HEDP therapy.

AIM: In this study, a new method has been used to predict pain response to (186)Re-HEDP therapy in patients suffering from painful osseous metastases, on the basis of a modified bone scan index and pre-therapy pain scoring. METHODS: Forty five patients received a total of 73 doses of (186)Re-HEDP during a period of pain relapse without extra-osseous disease progression. All patients were under stable regimen of zoledronic acid, far off other therapeutic manipulations. Imaging studies regarding a modified estimation of bone scan index, were applied; the value of the largest bony lesion (called mBSI), provided that it also corresponded to the most prominent site of osseous pain was taken into account, and a new semi-quantitative index called Double Product Value (DPV), equal to pre-therapy pain score times mBSI was entered in the result analyses, to investigate any possible correlations with response endpoints. RESULTS: Favourable response occurred in 35/47 evaluated therapeutic doses of (186)Re-HEDP (74.5%; excellent response in 12 doses, 25.5%). Responders had significantly lower DPV (3.4 ± 2.3 vs. 10.2 ± 6.2, P=0.0029, for non-responders). Patients with pre-therapy DPV 4, and also a longer median period of pain relief (respective mean values 5.9 versus 2.1 months, HR 2.82; P=0.0001). CONCLUSION: DPV, as developed and implemented in this study proved a valuable and reproducible pre-therapy tool for assessing degree and duration of pain response after (186)Re-HEDP therapy.

Extracellular domain of HER2: a useful marker for the initial workup and follow-up of HER2-positive breast cancer.

PURPOSE: The extracellular domain (ECD) of the HER2 receptor is proposed as a real-time marker of HER2-positive breast cancer (BC). In this study, ECD-HER2 levels were compared with standard clinical and pathological prognostic factors. PATIENTS AND METHODS: In 247 consecutive patients (116 with early or localized BC, 116 with advanced or metastatic BC, and 16 with benign mastopathies), serum ECD-HER2 levels were measured. In 116 advanced-disease patients ECD-HER2 status was also studied by immunohistochemistry (IHC) and compared with established clinical and pathological variables. RESULTS: Mean serum ECD-HER2 value was 19.62 ng/ml (median 10.35, range 3-->250). Mean value in benign mastopathies was 9.04 ng/ml, 9.4 ng/ml in early disease and 34.5 ng/ml in advanced disease. No difference between benign mastopathies and early BC was observed, while significant difference between early and advanced BC (p<0.001) was noted. However, in advanced-disease patients a positive correlation of ECD-HER2 with IHC (p=0.002), disease grade (p=0.034) and level II axillary node involvement (p=0.011) was noted, as well as a significant negative correlation with estrogen receptor (ER) and progesterone receptor (PR) (p=0.035 and p=0.011, respectively). CONCLUSION: ECD-HER2 is a reliable marker for breast cancer, as suggested from the existing literature; therefore, its integration in the initial workup and follow-up routine of breast cancer, particularly the HER2-positive, is proposed.

Non-allergic nature of docetaxel-induced acute hypersensitivity reactions.

Based on observations of a discrepancy between 'hypersensitivity' reactions to docetaxel (DT) and the clinical features of allergic reactions, we explored the hypothesis that DT-induced acute hypersensitivity reactions (AHRs) have a non-allergic origin. Forty cancer patients receiving DT and 16 patients receiving other potentially allergenic chemotherapeutic agents were included in the study. All DT patients received standard pre- and post-medication. Before, during and after administration of the drugs, clinical symptoms and signs were recorded, and serial blood sampling was performed for the first 2 cycles for all patients or in all subsequent cycles in case of AHRs. Plasma histamine and serum tryptase, two established drug allergy markers, were measured. Seventy-five chemotherapy sessions were evaluable. Nine patients on DT, two on paclitaxel (PT) and one on pegylated doxorubicin experienced an AHR during the first course of chemotherapy. In all cases, heart rate remained stable or increased, while arterial pressure was unchanged or raised; no hypotension or bradycardia was noted. All episodes resolved with discontinuation of drug and did not reappear during a re-challenge with the same agent 30 min later. Tryptase levels were normal in all pre- and post-exposure samples (post-exposure: 11.32+/-35.63 microg/l, normal values <13.5 microg/l). In all but one AHR-free PT, pre- and post-exposure histamine concentrations remained normal (post-exposure: 2.86+/-11.88 nM, normal values <10 nM). No eosinophilia or basophilia was observed. We conclude that 'hypersensitivity' reactions to DT seem not to be histamine or tryptase mediated; thus, their allergenic nature should be questioned. The underlying mechanism may be related to other biological processes such as the release of vasoactive molecules or non-histamine/tryptase-mediated allergy. If the former is demonstrated by further study, the safety of DT administration will be confirmed, and the pre- and post-medication practice might be revisited.

Strontium-89 chloride in the treatment of bone metastases from breast cancer.

Sixty-four patients with painful metastatic breast cancer in bone were treated with 2 MBq/kg of strontium-89 chloride as a single intravenous injection. Patients were followed with records of medication, hematology parameters, serial bone and Sr-89 bremsstrahlung images and with a point pain score scale (10-0). The response was assessed during a 6-month period of follow-up. Fifty-two of 64 patients (81%) showed at least a moderate improvement. Eighteen out of the 52 responders showed a dramatic decrease in bone pain (35%), 21 (40%) presented a satisfactory response and in 13 cases (25%) the response was moderate. Only 12 patients (19%) from the whole group did not feel any improvement on pain palliation. A statistically significant decrease of pretreatment levels of platelets and leukocyte counts was observed after 4-6 weeks of therapy in 50 (70%) patients. Although most patients showed no change in their bone scans after 3 months of treatment, an obvious improvement was observed in 3 of them. Furthermore no additional painful metastases on their bone scintigraphic images were observed. The selective strontium-89 local uptake in metastatic sites was also confirmed directly by bremsstrahlung scans which were absolutely comparable to the respective 99mTc bone scans. Precautions have been taken against Sr-89 contamination from the patients' blood or excretions.

Diagnostic significance of the tumour markers CEA, CA 15-3 and CA 125 in malignant effusions in breast cancer.

Concentrations of the tumour-associated antigens CEA, CA 15-3 and CA 125 were determined in serous effusions (EF) from patients (pts) with breast cancer. As controls, serous effusions from patients with benign and other malignant diseases were used. The EF levels were also compared with those of serum. CA 15-3 was elevated (greater than 35 U/ml) in 65.7% of breast cancer EF, in 39.3% of EF in various other malignant diseases and in 0% of benign EF. CEA was elevated (greater than 9 ng/ml) in 37.5% of breast cancer EF, in 17.9% of EF of various other malignant diseases and in 27% of benign EF. CA 125 was elevated (greater than 35 U/ml) in 93.8% of breast cancer EF, in 78.6% of EF of various other malignant diseases and in 58.8% of benign EF. There was a statistically significant correlation between EF and serum values for the markers studied. Sensitivity and specificity for CA 15-3 were 65.7% and 76.6%, for CEA 37.5% and 77.7% and for CA 125 93.8% and 28.7%, respectively. CA 15-3 is a marker with definite diagnostic accuracy compared to CEA and CA 125 in breast cancer EF. CA 125 appears to derive from proliferating mesothelia rather than cancer cells alone and occurs in a broad spectrum of malignant as well as benign EF. The above markers should not be used alone for diagnosis of breast cancer in patients with serous effusions.