Long-term outcome of mesna, ifosfamide, mitoxantrone, etoposide (MINE) regimen as a consolidation in patients with aggressive non-Hodgkin lymphoma responding to CHOP.

In aggressive non-Hodgkin lymphoma (NHL), CHOP (cyclophosphamide, vincristine, doxorubicin, prednisolone) regimen has been standard for decades, and rituximab has increased response rates and survival in CD20 positive patients, recently. The aim of this prospective trial was to evaluate the long-term efficacy and toxicity of MINE as a consolidation treatment in aggressive NHL patients who had achieved CR or unproven CR after six cycles of CHOP in the first line setting. The primary end-point was disease-free-survival (DFS). Thirty-eight patients were enrolled between February 1992 and May 2000. All of the patients received two cycles of MINE (mesna 1.3 g/m(2), ifosfamide 1.3 g/m(2), etoposide 65 mg/m(2) on days 1-3, and mitoxantrone 12 mg/m(2) on day 1, every 3 weeks) following response to CHOP. Initial bulky disease sites were also applied radiotherapy. Male/female ratio was 1.53(23/15). Median age was 49(30-73). Most of the patients had advanced stage (84.2% for stage >3) and high IPI score (79% for IPI score >2). Sixty percent had diffuse large cell histology. Median follow-up time was 118 months (9-195). Actual mean dose intensity was 88%. There were seven febrile neutropenia episodes. Two patients had grade two neuropathy, one had grade three mucositis and another one had non-neutropenic pneumonia. There was no early toxic death. No serious late toxicity was observed during long-term follow-up. Five- and 10-year DFS rates were both 65.3%. DFS rate in the patients with more than two poor prognostic factors according to IPI score is remarkably high (88%). Five- and 10-year OS was 62.5 and 59%, respectively. MINE regimen seems to be effective as a consolidation regimen, especially, in intermediate/high risk patients and has low early and late toxicities, and it warrants to be evaluated in phase III randomised trials with rituximab in CD20 positive aggressive NHL patients.

The impact of waist-to-hip ratio on clinical outcomes in metastatic breast cancer patients treated with aromatase inhibitors.

We aimed to identify whether abdominal fat distribution could affect the outcome in metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs) or not. A total of 42 MBC patients treated with first line hormonal therapy were enrolled in this study. Factors associated with overall survival in the univariate analysis were age, c-erb-B2 expression intensity (+++ versus others by immunohistochemistry), and WHR, whereas only WHR retained significance in the multivariate analysis. Median overall survival figures were 472 days versus unreached for patients with a WHR of <0.92 and >or=0.92 (Log rank statistic=9.76, P=0.002). Similarly, the corresponding progression free survival figures for patients with a WHR of <0.92 and >or=0.92 were 423 versus 1004 days (Log rank statistic=6.37, P=0.012). This study suggests that WHR may serve as a potential predictive marker in MBC patients treated with AIs.

Factors related to truth-telling practice of physicians treating patients with cancer in Turkey.

BACKGROUND: In the practice of oncology, effective communication between physician and patient is very important. Although many studies have indicated that a large majority of physicians, especially from Western countries, tell the truth about diagnosis and prognosis, little is known about attitudes of physicians in Turkey toward truth-telling. OBJECTIVE: In this study, we tried to determine the truth-telling practice of physicians and explore potential related factors with a self-reported questionnaire. DESIGN: Using a questionnaire, 131 cancer specialists were interviewed during the 15th National Oncology Meeting in April 2003. RESULTS: The percentage of physicians who never, rarely, generally, and always prefer truthtelling about a cancer diagnosis were 9%, 39%, 45%, and 7%, respectively. In univariate logistic regression analysis for the truth-telling practice, significant variables included "do not tell" requests from family, experiences from medical training and clinical practice, and medical specialty. In the multivariate analysis, "do not tell" requests from relatives and medical training factors retained their significance. CONCLUSION: Professional training in breaking bad news is important and is associated with the self-reported truth-telling practices of physicians.

Quality of life in patients with advanced non-small cell lung cancer.

Quality of life (QOL) has been shown to improve with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), but the determinants of this improvement have not been thoroughly explored. Fifty consecutive NSCLC patients starting chemotherapy with measurable disease and with an Eastern Co-operative Oncology Group (ECOG) performance status of

Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrug resistance protein-1 dependent way: an in vitro study.

We have explored the action of zoledronic acid, which has an apoptotic effect and is used as an agent for treating skeletal metastases and osteoporosis, in the presence of vinblastine, and whether this effect is associated with MRP-1 (multidrug resistance protein-1) expression. HEK (human embryonic kidney) 293 cells were transfected to form the multidrug resistant cell line designated 293MRP (MRP-1 expressing HEK293 cells). Both lines were treated with varying concentrations of vinblastine and zoledronic acid. Apoptosis was determined by the TUNEL (deoxyuridine triphosphate nick end-labeling) method. The type of treatment, MRP-1 expression status, and the type of treatment with respect to MRP-1 expression status significantly affected (P < 0.001) the degree of apoptosis. The largest increase in cytotoxicity was noted in HEK293 cells, when 100 micromol zoledronic acid was added to 4 microg/ml vinblastine (an increment of 80.3%, P < 0.001). This preliminary work shows that zoledronic acid acts synergistically with vinblastine to induce apoptosis in an MRP-1 dependent way.

Different clinical features of primary and secondary tumors in patients with multiple malignancies.

Clinical features of the first and second primaries in patients with multiple malignancies have not been extensively studied. We compared patient and treatment characteristics of the primary malignancy in 48 consequent multiple primary cancer patients with those of the second primary in the same cohort. The second primaries comprised fewer breast cancers; 29.2% of primaries as opposed to 10.4% of second tumors were breast cancer (P = 0.049). In addition, primary tumors tended to be at a lower TNM stage than secondary tumors (P = 0.060). The median overall survival after the diagnosis of the first primary for the whole cohort was 22.3 years (95% CI, 2.0-42.5) and the median time to presentation of the second malignancy was 38 months after the diagnosis of the first primary (range, 0 to 384). Therefore, the prognosis of cancers in the multiple malignancy group appears to be good and they appear to have an indolent clinical behavior. Thus, we recommend a long screening time for secondary tumors after a curative treatment in patients with common cancers, taking into account the different occurrence patterns of second primaries with respect to first primaries.

Cluster analysis of p-glycoprotein, c-erb-B2 and P53 in relation to tumor histology strongly indicates prognosis in patients with operable non-small cell lung cancer.

BACKGROUND: Various biomarkers have prognostic value in non-small cell lung cancer (NSCLC). We aimed to identify the roles of P53, c-erb- B2 and p-glycoprotein (pgp) as prognostic factors, independently or in conjunction with each other, in operable NSCLC. MATERIAL/METHODS: Seventy operable NSCLC cases were retrospectively evaluated for P53, c-erb-B2 and pgp expression patterns by immunohistochemistry. An unsupervised hierarchical cluster analysis of the 3 biomarkers was conducted. Univariate and multivariate survival analyses were made in relation to cluster affiliation. RESULTS: Cluster analysis yielded two distinct subgroups; group A of high biomarker expressors (n=26, 37%), and group B (n=44, 63%) of low expressors. Cluster affiliation with regard to tumor histology (interaction term) was independently associated with Recurrence- free survival (RFS) and Overall survival (OAS) with a Hazard Ratio (HR) of 5.88, P=0.003, and HR=4.68, P=0.012, respectively. The median OAS times for cluster A and B in the squamous cell carcinoma subgroup were 328 and 596 days, whereas the corresponding figures in the non-squamous cell carcinoma subgroup were non-measurable and 298 days. CONCLUSIONS: In operable NSCLC there may be different relationships of P53, c-erb-B2 and pgp with patient outcome for different tumor histologies. The prognostic utility of cluster affiliation with regard to these biomarkers, and in relation to tumor histology, deserves further testing.

Tumour necrosis factor-alpha, interleukin-6, and fasting serum insulin correlate with clinical outcome in metastatic breast cancer patients treated with chemotherapy.

INTRODUCTION: To assess the relationship of various growth factors and cytokines with the clinical outcome in metastatic breast cancer patients receiving chemotherapy. METHODS: Consecutive, metastatic breast cancer patients with measurable disease and receiving palliative chemotherapy were prospectively evaluated for the predictors of progression free survival (PFS) and overall survival (OAS) in relation to serum insulin, insulin resistance, interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha). RESULTS: Estrogen receptor (ER) status, serum IL-6 and serum TNF- were the independent determinants of PFS, with RR=0.28 (0.13-0.60), P=0.001, RR=2.48 (1.24-5.61), P=0.012, and RR=0.48 (0.23-1.01), P=0.053, respectively. The factors related with OAS in the multivariate analysis were histological grade (RR=7.88 (2.33-26.62), P=0.001), ER status (RR=0.18 (0.06-0.57), P=0.003), serum insulin (RR=0.87 (0.77-0.97), P=0.016), and serum IL-6 (RR=5.99 (1.89-18.97), P=0.002). CONCLUSIONS: We show for the first time that fasting serum insulin and TNF-alpha levels are independent predictors for OAS and PFS, respectively, in metastatic breast cancer patients. In addition, we also confirm that IL-6 is a poor prognosticator in this group. These results suggest that insulin and TNF-alpha are important biomolecules that may be directly involved in vivo in the progression of metastatic breast cancer.

"Do not tell": what factors affect relatives' attitudes to honest disclosure of diagnosis to cancer patients?

Disclosure of the diagnosis of cancer to patients is a difficult task for physicians in developing countries. Family members often oppose truth telling. The aim of this study was to evaluate the incidence of the "do not tell" attitude in a general population of cancer patients and to explore the factors affecting the attitude of cancer patients' relatives about honest disclosure. Using a questionnaire, relatives of 150 patients with recently diagnosed cancer were interviewed. Of the relatives, 66% did not want the diagnosis to be disclosed. Male gender of the patient, a diagnosis of a non-breast cancer malignancy, the presence of stage IV disease, no previous request for disclosure by the patient, insufficient knowledge of the relative about cancer in general, and stronger religious belief of the relative were associated with greater likelihood of the relative having a "do not tell" attitude in univariate analyses ( P=0.032, P=0.000, P=0.051, P=0.021, P=0.128, and P=0.058, respectively). In a multivariate analysis, the diagnosis of a non-breast cancer malignancy, and insufficient knowledge of the relative about cancer in general retained their significance (exp(B)=14.77, P=0.000; exp(B)=3.04, P=0.01, respectively). Differences among different countries and cultures are discussed.

Durable remission of leptomeningeal metastasis of breast cancer with letrozole: a case report and implications of biomarkers on treatment selection.

We report a breast cancer patient with leptomeningeal carcinomatosis (LM) who showed an excellent objective and subjective response to letrozole, with a progression-free survival of 16 months. We think that despite the poor prognosis and short survival of patients with LM, early diagnosis and treatment with appropriate hormonal manipulation may improve the outcome and achieve prolonged palliation in selected hormone-positive breast cancer patients with LM. Possible clues predicting the response were also evaluated in the context of literature data.