Safety and efficacy of transdermal fentanyl in patients with cancer pain: phase IV, Turkish oncology group trial.

We have performed a prospective evaluation of the efficacy, safety and convenience of the transdermal therapeutic system - fentanyl (TTS-F) in Turkish cancer patients when it was newly available in Turkey. Ninety-nine patients with historically confirmed malignancy and pain entered the study; the mean age was 55.1 (16-58) years. The study duration was 28 days. Transdermal therapeutic system - fentanyl was used in opioid-naïve or pre-treated patients. Most patients reported a decrease in pain severity. Use of rescue medication decreased from day 4 to day 28. The majority of patients rated patch convenience of use as excellent. A total of 22.2% of patients experienced adverse events that were either probably related or very likely to be related to the study drug. The majority of the adverse events mentioned were related to the digestive system. Eighteen serious adverse events were reported by 13 patients. Six events were doubtfully related, and 12 events were not related to the study drug. Four patients died during the trial. None of these deaths was attributed to the study drug. In conclusion, the trial showed that TTS-F is easily managed, effective and will help to enable the appropriate opioid administration to patients who are suffering from cancer pain in Turkey.

Pre-treatment haemoglobin concentration is a prognostic factor in patients with early-stage breast cancer.

We investigated the prevalence of anaemia (haemoglobin concentration < 12 g/dl) in 336 women with early-stage breast cancer and its association with other known prognostic factors. The median follow-up period was 60.5 months (range 9 - 123 months). Seventy-nine women (23.5%) had a low pre-treatment haemoglobin concentration, but anaemia was not correlated with age, tumour size, nodal status, histological grade or hormone receptor status. Univariate analysis revealed that disease-free survival and overall survival were shorter in patients with anaemia at the time of diagnosis than in patients with normal haemoglobin concentrations. Anaemia remained a significant prognostic factor for disease-free survival and overall survival in the multivariate analysis (relative risk, 1.884 and 1.785, respectively). These results suggest that pre-treatment haemoglobin concentration is an independent prognostic factor in patients with early-stage breast cancer.

Prognostic significance of thrombocytosis in node-negative colon cancer.

Several clinical studies have shown that thrombocytosis is a poor prognostic factor in some types of cancer, but data about the impact of thrombocytosis on prognosis in patients with colon cancer are very limited. We investigated the prevalence and prognostic effect of pre-operative thrombocytosis, defined as a platelet count > 400 x 10(9)/l, retrospectively in patients with node-negative colon cancer. Out of 198 patients, 24 (12.1%) had thrombocytosis, and its presence correlated with tumour depth and lymphatic invasion. Univariate analysis revealed that disease-free survival and overall survival were shorter in patients with pre-operative thrombocytosis than those without thrombocytosis. On multivariate analysis, thrombocytosis alone retained significance as a poor prognostic factor for both disease-free survival and overall survival. In conclusion, this study shows an association between thrombocytosis and poor survival in patients with node-negative colon cancer. The preoperative platelet count may help to identify patients with an unfavourable prognosis in this subgroup.

Prevalence and prognostic value of c-erbB2 expression in non-small cell lung cancer (NSCLC).

The c-erbB2 oncoprotein is highly expressed in approximately one third of non-small cell lung cancer (NSCLC) patients. We determined the status of c-erbB2 expression in our patients with NSCLC and investigated its correlation with disease stage, histological type and response to treatment. Eighty-four patients were examined for the expression of c-erbB2 by immunohistochemistry using a polyclonal antibody. The scoring criteria of Clinical Trial Assay (CTA) were used to evaluate staining (0 to +3). c-erbB2 overexpression was determined in 35% of the cases. Tumors from higher stage disease (stage IIIb-IV) were more often c-erbB2 positive in adenocarcinoma (ADC) (p=0.04). In addition, there was an association between c-erbB2 score and disease stage in ADC patients (p=0.03). Our study did not demonstrate an association of c-erbB2 overexpression with response to chemotherapy. We conclude that c-erbB2 overexpression may be a prognostic marker for evaluating tumor progression in NSCLC patients but further studies must be performed with larger patient populations.

Chemotherapy- and radiotherapy-induced cytologic alterations in the sputum of patients with inoperable lung carcinoma. Role in follow-up.

OBJECTIVE: To define the light microscopic cytologic changes due to chemotherapy (CT) and/or radiotherapy (RT); to evaluate the differentiation of those changes according to treatment; to find out whether a relation exists between treatment type and its duration and the cytologic findings; and to determine the role of sputum cytology in evaluating efficacy of treatment and follow-up in patients with inoperable lung cancer of various histology. STUDY DESIGN: A total of 1,605 periodic sputum samples from 80 cases of lung cancer obtained during treatment and follow-up were prospectively examined cytologically. The relationship of treatment type and duration to qualitative and semiquantitative data and the definability of the response to treatment as well as the relationship of progression-free survival (PFS) and total survival (TS) rates with cytologic data were evaluated. RESULTS: The majority of therapy-induced cellular changes were in the nucleus and were directly related to the duration of treatment. An increase in minimally affected tumor cells, tumor cells that lost their pathologic features and necrotic cell debris were good indicators of therapeutic efficacy. Cytologic changes did not reflect PFS and TS rates. CONCLUSION: Although light microscopic cytologic changes cannot be attributed objectively to either RT or CT, therapeutic efficacy is shown in follow-up sputum cytology, which can be used in monitoring and planning additional therapy or other therapeutic options in lung cancer patients.

Extensive extramedullary disease in myeloma. An uncommon variant with features of poor prognosis and dedifferentiation.

BACKGROUND: The development of extramedullary plasmacytomas and elevated serum lactic dehydrogenase (LDH) in myeloma indicates poor prognosis. A 75-year-old man was diagnosed with immunoglobulin (Ig) A, lambda myeloma when he developed pathologic rib fractures, hypercalcemia, and anemia. After 6 months of treatment with melphalan and prednisone, he was in complete remission as evidenced by the disappearance of the monoclonal protein in the serum and free light chain in the urine. Eight months after diagnosis, his disease took an unusual course with the simultaneous development of plasmacytomas in the skin, breast, stomach, and pancreatic head, complicated by severe upper gastrointestinal bleeding and obstructive jaundice. METHODS: Immunohistochemical staining of the marrow and breast mass was done using monoclonal antibodies against B-cell and T-cell antigens as well as kappa and lambda light chains. In situ hybridization was performed to detect ras oncogene overexpression in the breast mass. RESULTS: Immunohistochemical staining of the original marrow and breast mass was positive for IgA and lambda, confirming the identical clonal origin of the plasma cells. The disorder expressed elevated serum LDH, both at diagnosis and relapses. Features of dedifferentiation were expressed by the disappearance of myeloma protein in the serum at relapse, absence of marrow plasma cell infiltration, and development of multiple extramedullary plasmacytomas. There was no overexpression of H-ras or N-ras oncogenes by in situ hybridization of the plasmacytoma from the breast. The patient died shortly after the development of the extramedullary plasmacytomas. CONCLUSIONS: The simultaneous appearance of plasmacytomas in multiple extramedullary sites heralds a change of clinical behavior in myeloma. When accompanied by the disappearance of serum myeloma protein, and marrow plasma cell infiltration, and serum LDH elevation, the disorder may follow a fulminant course.