Predictive role of midtreatment changes in survivin, GSTP1, and topoisomerase 2α expressions for pathologic complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.

INTRODUCTION: The primary aim of this study is to investigate the effect of change in the expression levels of survivin, glutathione-S-transferase P1 (GSTP1), and topoisomerase 2α (TOP2A) on the response to antracyclin-based and taxane-based neoadjuvant chemotherapy. METHODS: This study included 32 locally advanced breast cancer patients. Tumoral expressions of survivin, TOP2A, and GSTP1 in serial biopsy specimens obtained before treatment, after sequential 4 cycles of doxorubicin+cyclophosphomide, and 4 cycles of docetaxel were analyzed by real-time polymerase chain reaction. Survivin expressions were additionally analyzed in serial blood samples. RESULTS: The pathologic complete response (pCR) rate and the overall response rate (clinical complete and partial) were 28% (n=9) and 91% (n=29), respectively. There were no statistically significant correlations between serial TOP2A expression levels and response. There was a nonsignificant trend toward an improved response rate with decreased survivin expression. A significant decrease in the GSTP1 expression level throughout treatment (P=0.014), which was also shown to be significantly correlated with a pCR (P=0.0001), was seen. Downregulation of GSTP1 after 4 cycles of anthracycline-based combination was independently associated with improved progression-free survival (P=0.01). CONCLUSIONS: Downregulation of GSTP1 is a significant predictor of pCR and improved progression-free survival during anthracycline-based and taxane-based neoadjuvant chemotherapy in patients with locally advanced breast cancer.

The roles of surgery and EMA/CO chemotherapy regimen in primary refractory and non-refractory gestational trophoblastic neoplasia.

PURPOSE: To determine the characteristics and outcome of patients with refractory gestational trophoblastic neoplasia (GTN) after primary chemotherapy (CTx). METHODS: The outcome of low- and high-risk patients with refractory GTN (n = 14, 37%) was compared to those with non-refractory GTN (n = 24, 63%). Methotrexate treatment was used for patients with low-risk disease and EMA/CO for patients with high-risk disease. RESULTS: Median follow-up time was 53 months (range 1-173 months). All non-refractory patients and 11 refractory patients (79%) survived (p = 0.015). Factors related to resistance to primary CTx was age (p = 0.012), duration between causal pregnancy and initial treatment (p = 0.003), surgery (p = 0.014), hCG level before CTx (p = 0.09) and half-life of hCG (p = 0.061). Six out of 10 low-risk refractory patients treated with EMA/CO regimen in the second-line setting had been followed by no evidence of disease. Nine of 38 (24%) patients underwent surgery (TAH ± BSO) for GTN. All of the patients treated with surgery were in the non-refractory group, but none of refractory patients underwent surgery (p = 0.014). CONCLUSIONS: Surgery and EMA/CO regimen are one of the main factors that play a role in the management of refractory low-risk GTN.

Association of clinical and pathological variables with survival in thymoma.

Our aim was to evaluate clinical and pathological features in prognosis of thymoma patients with particular emphasis on patients with myasthenia gravis (MG). From 1995 to 2010, 140 thymoma patients (women/men: 63/77) with a median age of 46 years (11-80 years) were admitted to our institution. According to World Health Organization (WHO), there were 23 (17%) type A, 12 (9%) type AB, 24 (17%) type B1, 42 (31%) type B2 and 36 (26%) type B3. The distribution of Masaoka stages I, II, III and IV was 24 (17%), 71 (51%), 18 (13%) and 27 (19%), respectively. MG coexisted in 61% of patients. After a mean follow-up of 34 months (1-158 months), 102 (73%) patients are alive and well while 14 (10%) are alive with disease. Twenty-three patients (16%) have died, only 9 died of thymoma. In univariate analyses, completeness of resection (P < .001), WHO histology (P = .008), Masaoka stage (P < .001) and MG (P = .002) were significant prognostic factors for progression-free survival (PFS). Young age (P = .008); Masaoka stages 1 and 2 (P = .039); WHO types A, AB and B1 (P = .031); complete resection (P = .024) and presence of MG (P = .05) significantly correlated with overall survival (OS). In multivariate analysis, Masaoka stages 1 and 2 (P = .038) and presence of MG (P = .01) were significantly correlated with a longer PFS; MG (P = .021) and WHO subtype (P = .022) were found to be significant prognostic factors for OS. Adjuvant radiotherapy improved neither OS nor PFS in completely resected stage 2 thymoma. Masaoka staging, WHO and MG are major determinants of prognosis in Turkish thymoma patients. Additionally, radiotherapy did not provide survival advantage to stage 2 patients with complete resection.

Clinical and pathological features of breast cancer associated with the pathological complete response to anthracycline-based neoadjuvant chemotherapy.

OBJECTIVE: Patients with breast cancer with a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have a better prognosis than patients with residual disease. The aim of the current study was to identify predictors of pCR. METHODS: This retrospective study included 388 patients treated with anthracycline-based NAC. Clinicopathological parameters were compared between the patients with and without pCR in breast and axilla. RESULTS: Treatment consisted of FAC/FEC in 230 patients (59%), TAC in 39 (10%) patients and AC followed by docetaxel in 119 (31%). In all, 36 (9.3%) patients had pCR. In univariate analysis, age, tumor size, lymph node involvement, tumor grade (p = 0.077, n = 265), ER and HER-2 status (n = 213), lymphovascular invasion (LVI), type of chemotherapy and taxane-containing chemotherapy were associated with pCR. In multivariate analysis, ER negativity (p = 0.003), the absence of LVI (p = 0.009) and taxane-containing NAC (p = 0.026) were found to be significant indicators of pCR. Median follow-up time was 69 months. Progression-free survival was significantly improved in patients achieving pCR (p = 0.001). CONCLUSIONS: pCR is associated with a better outcome regardless of clinical and pathological parameters in breast cancer patients who receive NAC. The probability of pCR was higher in ER-negative, LVI-negative tumors and in patients treated with sequential taxane-containing chemotherapy.

Paraoxonase-1 192/55 polymorphisms and the risk of lung cancer in a Turkish population.

AIM: The purpose of the present study was to investigate the possible association of paraoxonase-1 (PON1) 192/55 polymorphisms with lung cancer (LC) risk in a Turkish population. MATERIALS AND METHODS: A population-based, case-control study was carried out, including 223 patients with LC and 234 controls. The frequencies of PON1 192/55 genotypes were compared in patient and control groups using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Distribution of PON1 192 R (+) genotype was found to be significantly higher in patients with LC compared to the controls (odds ratio: 1.497, 95% confidence interval: 1.034-2.166). This difference was especially noteworthy in patients with small cell carcinoma and squamous cell carcinoma. CONCLUSION: This is the first case-control study on the association between PON1 polymorphisms and LC susceptibility in a Turkish population. Our results suggest that PON1 192 polymorphsim is associated with an increased risk of LC in the Turkish population and may be a useful genetic marker for small cell and squamous cell carcinoma.

The role of antibiotic prophylaxis in totally implantable venous access device placement: results of a single-center prospective randomized trial.

BACKGROUND: This study evaluated whether prophylactic treatment with a cefazolin could prevent infections in patients who had a surgically inserted totally implantable venous access device (TIVAD). METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial comparing wound infection rates in 404 patients (203 received prophylactic cefazolin, 201 received a placebo) undergoing TIVAD insertion. Infections were evaluated 3, 7, 14, and 30 days after discharge and outcomes were compared and analyzed. RESULTS: Groups were well matched for all preoperative variables studied, including comorbid conditions. Superficial surgical site infection developed in 5 patients (2.5%) from the antibiotic group and 6 (3%) from the placebo group (P = .75). One from each group developed deep surgical site infection. Both patients were readmitted and underwent repeated debridement, which eventually resulted in port loss in 1 patient. CONCLUSIONS: We do not recommend the use of prophylactic antibiotics in TIVAD insertion because they will not decrease the already low rate of postoperative infectious complications. Registration number NCT00867295 (http://www.clinicaltrials.gov).

Weekly docetaxel and cisplatin with concomitant radiotherapy in addition to surgery and/or consolidation chemotherapy in stage III non-small cell lung cancer.

PURPOSE: The aim of this study was to evaluate efficacy and feasibility of a combination of weekly docetaxel and cisplatin administered concomitantly with radiotherapy followed by surgery in addition to consolidation chemotherapy with docetaxel and cisplatin administered every 3 weeks in stage III non-small cell lung cancer (NSCLC). METHODS: A total of 31 histologically proven, locally advanced (stage IIIA-N2 = 9, stage IIIB-T4N0-2 = 22) NSCLC patients were investigated. After administration of 4-6 cycles of weekly docetaxel (20 mg/m(2)) and weekly cisplatin (20 mg/m(2)) concurrently with radiotherapy, patients underwent operation if their disease was appropriately downstaged. Combination chemotherapy with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks was administered as a consolidation regimen. The treatment response, toxicity, time to progression (TTP) and overall survival (OS) were evaluated. RESULTS: After concomitant chemoradiotherapy, complete response and partial response occurred in 16.1 and 67.7% of patients, respectively. Thirteen percentage of patients progressed on treatment, and 3.2% had stable disease. Grade 3-4 hematologic and skin toxicities did not occur, whereas 17.9% of them experienced grade 3-4 oesophageal toxicity. Grade 3 pulmonary toxicity and grade 3-4 emesis developed in 9.7 and 6.4% of patients, respectively. Thirteen responsive patients (41.9%) underwent surgery. The toxicity of consolidation chemotherapy was tolerable. Median OS and TTP were 22 ± 5 (range 13-31) and 12 ± 3 (range 7-17) months, respectively. Median follow-up was 22 (range 2-57) months. CONCLUSIONS: Weekly administration of docetaxel and cisplatin concurrently with radiotherapy followed by consolidation chemotherapy is an effective treatment with acceptable toxicity for patients with locally advanced NSCLC especially in combination with surgery.

Non-pharmacological interventions used by cancer patients during chemotherapy in Turkey.

PURPOSE: Although there are many non-pharmacological practices being recommended for symptom management, most patients prefer to use pharmacological interventions. This study assesses the non-pharmacological interventions used by cancer patients for symptom management during chemotherapy and the factors affecting its use. METHOD: This study was conducted at the Istanbul University Institute of Oncology, Turkey, with 202 patients. Personal characteristics, illness-related characteristics, symptom severity and non-pharmacological interventions used by the patients were assessed by using Patient Description Form, ECOG and Nightingale Symptom Assessment Scale. RESULTS: Most of the patients in this study were living in Istanbul, 58.4% were women, 78.7% were married and their mean age was 48.82 ± 1.44. Most of the patients experienced different symptoms related to chemotherapy, but only a small number of patients preferred to use and benefited from the non-pharmacological interventions in their symptom management. There were different factors affecting the well-being of the patients, but only being young was found to be an important variable in the use of psychological interventions (OR 3.06 [95% CI 1.17-7.96]). CONCLUSIONS: Physicians remain the central figure in the treatment of cancer patients, so oncologists and oncology nurses should be more proactive and innovative in their patient care, education, and counseling to maximize the use of non-pharmacological interventions that may be helpful in symptom management. Further research evaluating the use and effectiveness of non-pharmacological interventions on symptom management in cancer patients is needed.

Effect of kefir on the quality of life of patients being treated for colorectal cancer.

PURPOSE/OBJECTIVES: To determine kefir's effect on the prevention of gastrointestinal complaints and quality of life (QOL) in patients being treated for colorectal cancer. DESIGN: Randomized, controlled, prospective, interventional study. SETTING: Istanbul University Oncology Institute in Turkey. SAMPLE: 40 patients, 20 of whom were randomized to the experimental (kefir) arm and 20 who were randomized to the control arm. METHODS: Informed consent to participate in the study was obtained. Before treatment began, demographics, illness-related characteristics, complaints, and QOL of participants were evaluated. During treatment, side effects were evaluated one week after every cycle of therapy. QOL was evaluated after the third and sixth cycles of treatment. MAIN RESEARCH VARIABLES: The effect of kefir on the prevention of gastrointestinal complaints and QOL in patients being treated for colorectal cancer. FINDINGS: Following chemotherapy, the experimental (kefir) group had more treatment-related gastrointestinal complaints but a decrease in sleep disturbance. No difference was found between the two groups for QOL. CONCLUSIONS: Kefir does not prevent or decrease gastrointestinal complaints in patients undergoing chemotherapy for colorectal cancer. Kefir did decrease sleep disturbances in the experimental group. IMPLICATIONS FOR NURSING: Many patients use complementary and alternative medicine during cancer therapy. This study may provide information about the effectiveness of kefir in patients with cancer.

Serum levels of interleukin-6 and interleukin-10 in Turkish patients with aggressive non-Hodgkin's lymphoma.

There exists strong evidence that tumor growth can be actively controlled by the host immune system and interleukins are known to play a significant role in immune response regulation. Inflammatory cytokines play important roles in the pathogenesis of lymphomas. This study was conducted to investigate the serum levels of IL-6 and IL-10 in patients with aggressive non-Hodgkin's lymphoma (A-NHL) and the relationships with prognostic parameters and therapy. These serum factors were measured in 46 A-NHL patients pathologically verified before and after chemotherapy in comparison with 21 healthy controls using enzyme-linked immunosorbent assays (ELISAs). There were significant differences in the serum IL-10 and IL-6 levels between A-NHL patients and controls (p= 0.038 and p<0.001, respectively). None of the prognostic parameters analyzed was significantly correlated with the serum IL-6 concentrations. This was also true for serum IL-10 values, except for LDH and bone marrow involvement. Serum IL-10 levels were elevated in the group of patients with high level LDH compared with the group of patients with a normal level (p= 0.017). Also, serum IL-10 levels were significantly different in the presence or absence of bone marrow involvement (p= 0.016). In addition, we found a significant relationship between the serum levels of serum levels of IL-6 and IL-10 in patients with A-NHL (r= 0.47, p<0.001). We found that serum IL-10 levels decreased due to chemotherapy effect independent of the chemotherapy response (p= 0.027). However, serum IL-6 levels were not changed. In conclusion, our data suggest that higher serum IL-6 and IL-10 levels can be useful for diagnosis of A-NHL. However, our sample size is small, and larger scale research is needed in this field to provide new knowledge.

Factors related to recurrence after pathological complete response to postoperative chemotherapy in patients with epithelial ovarian cancer.

AIMS AND BACKGROUND: It has been appreciated for some time that the lack of detection of ovarian cancer at clinical and pathological (second-look laparotomy) evaluation is not synonymous with cure. The goal of this study was to define clinical risk factors for recurrence after complete pathological response to postoperative chemotherapy in patients with epithelial ovarian cancer. METHODS: Fifty-seven patients who met the inclusion criteria of our study were evaluated. The characteristics (age, menopausal status, histological subtype, tumor grade, presence of ascites at diagnosis, type of omentectomy, FIGO stage, and residual tumor volume after primary surgery) of patients with and those without tumor recurrence were compared. RESULTS: The median follow-up was 52 months (range, 15-142 months). The overall survival rates of the patients were 100%, 96%, and 87% at 1, 3 and 5 years, respectively. At the time of the study analysis, 21 of 57 (37%) patients had recurrent disease. The median time to recurrence was 16 months. Recurrences were most frequent in the pelvis and abdominal cavity (38%). Age, menopausal status, stage at diagnosis, and residual tumor volume after initial surgery were significantly related to the risk of recurrence in univariate analysis (P = 0.039, 0.038, 0.004, and 0.000, respectively). Residual tumor volume after initial surgery was found to be the only significant independent prognostic factor (P = 0.049, HR: 0.16, 95% CI: 0.02-0.99). CONCLUSION: We believe it is necessary to conduct randomized studies on this issue because insight into predictors of recurrence after pathological complete response to postoperative chemotherapy could be used to select patients for trials of consolidation therapy.

Yolk sac tumours of the ovary: evaluation of clinicopathological features and prognostic factors.

OBJECTIVE: To evaluate the clinicopathological prognostic features, factors and outcomes of chemotherapy in ovarian yolk sac tumours (YST). STUDY DESIGN: We reviewed the medical records of 32 women with ovarian YST treated from 1990 to 2006 at two centres. RESULTS: The median follow-up was 36 months. The median age was 22 (range, 9-68). Two patients were postmenopausal. The most common symptoms at diagnosis included abdominal swelling or mass (72%) and abdominopelvic pain (62%). The location of the tumour was bilateral in 2 cases. Eight patients were in stage I, 4 patients in stage II, 17 patients in stage III, and 3 patients in stage IV. Eighteen patients underwent unilateral salpingo-oophorectomy, two bilateral salpingo-oophorectomy and two cystectomy, while 10 patients had total abdominal hysterectomy and two bilateral salpingo-oophorectomy. Of 32 patients who received postoperative chemotherapy, 27 were treated with a bleomycin/etoposide/cisplatin (BEP) regimen. Seventy-two percent of patients were alive at the last follow-up visit. Ten (31%) patients suffered from a recurrence of the disease with a median time to recurrence of 8 months (range, 6-28 months). The most common site of recurrence was the intra-abdominal space, with 8 patients. Only one patient who had recurrence could be salvaged. Fertility-sparing surgery was found at least as effective as radical surgery. While age, histology (mixed vs. pure), stage, tumour size, ascites, and marker levels were not found as prognostic factors, the presence of residual tumour (P=0.014) and BEP chemotherapy (P=0.016) were significant prognostic factors in univariate analysis. CONCLUSIONS: In patients with ovarian YST, fertility-sparing surgery is as effective as radical surgery. Optimal cytoreductive surgery and standard BEP regimen are the most decisive prognostic factors. In these tumours, adjunctive therapeutic modalities to eradicate intra-abdominal disease and effective salvage therapy strategies are needed.

Quality of life and complementary and alternative medicine use among cancer patients in Turkey.

AIM: The purpose of this study was to assess the relationships between quality of life and use of complementary and alternative medicine (CAM) among Turkish cancer patients. METHODS: This cross-sectional study was conducted in Istanbul University Institute of Oncology, Turkey. Two-hundred patients were invited and informed consent was obtained, however 179 cancer patients completed the study. The Patient Characteristics form, The Nightingale Symptom Assessment Scale and The Functional Assessment of Cancer Therapy Scale were used in the evaluation of the patients' characteristics and quality of life. RESULTS: Some form of CAM had been used by 71.5% of the sample. Frequently used CAM methods appeared to be religious practices (68.2%) and only 37.4% of the patients used herbs. However, female patients, single patients, and individuals with metastatic disease and worse quality of life showed a tendency to use CAM more often. More than one-third of our patients began to use CAM immediately after being diagnosed with cancer and factors associated with CAM use varied according to the type of CAM. Although CAM use did not affect the patients' quality of life, logistic regression analysis revealed that gender, type of cancer diagnosis and education level were important factors to be considered in different CAM therapies. CONCLUSION: CAM use is common in cancer patients in Turkey. More discussion about CAM use should take place between patients and health professionals to inform the patients' decisions.

Malignant ovarian germ cell tumors: a single-institution experience.

OBJECTIVE: To evaluate the clinicopathologic prognostic factors in malignant ovarian germ cell tumors. METHODS: We reviewed the medical records of 70 patients treated from 1990 to 2006 at our center. Clinical data including demographics, stage, surgery, chemotherapy, survival, menses status, and fertility were collected from patients' charts. RESULTS: Median age was 22 years (range, 9-68). The histologic subtypes included 36 dysgerminomas, 11 yolk sac tumors, 3 immature teratomas, 1 embryonal carcinomas, and 19 mixed types. The most striking clinicopathologic finding was a history of concomitant immunosuppressant therapy, which was observed in 2 patients. Two patients had contralateral sex-cord tumors at presentation and follow-up. During a median follow-up period of 4.6 years, 11 patients had recurrence. The median time to recurrence was 8 months (6-28 months). Recurrences appeared in the abdominopelvic cavity in 9 out of 11 patients. Only one could be salvaged with second-line chemotherapy. Cumulative survival rate was 97% and 60% in patients with dysgerminoma and nondysgerminoma, respectively. Nondysgerminoma histology and residual tumor after surgery were unfavorable prognostic factors (P < 0.001 and P = 0.015). Fertility-sparing surgery was as effective as radical surgery among all eligible patients. Of patients with known menstrual status, 96% had regular menses. Of the 8 patients who opted for conception among these patients, 7 delivered healthy infants. CONCLUSIONS: Nondysgerminomas have an aggressive clinical course. New treatment strategies are needed for eradication of abdominopelvic disease at initial diagnosis and recurrent setting. Occurrence of malignant ovarian germ cell tumors may be associated with immunosuppression in some patients. Sex-cord stromal tumors may present with bilateral involvement. It is possible to maintain fertility after fertility-sparing surgery followed by chemotherapy.

Identification of patients who may benefit from the prophylactic cranial radiotherapy among breast cancer patients with brain metastasis.

BACKGROUND: To identify the candidates for prophylactic cranial radiotherapy (PCI) among the patients with early and advanced-stage breast cancer. METHODS: The demographic, pathologic and clinical features and survival results of 182 brain metastatic breast cancer patients treated with cranial radiotherapy were examined. RESULTS: Early stage patients who progressed with isolated brain metastasis had longer survival (13 months vs. 4 months P = 0.006). Lobular/mixed type histology (P = 0.033), high nuclear (P = 0.046) and high histological grade (P = 0.034) were the prognostic factors for isolated brain metastases. The most significant factor for the time to brain metastasis was the number of involved of lymph nodes (P = 0.004). In 60% of 148 patients with metastatic breast cancer, a progression with isolated brain metastasis was developed while the systemic disease was under control. Isolated brain metastasis progression was related to the presence of the hepatic metastasis at the first relapse (P = 0.001) and with ErbB-2 overexpression (P = 0.034). The time to the brain metastasis from the first extracerabral metastasis was associated with the high nuclear grade (P = 0.040) and with chemoresistance (P = 0.037). The median survival time after the brain metastases in chemosensitive patients was longer than in chemoresistant patients (8 months vs. 3 months P = 0.044). In chemoresistant patients (P = 0.0028) and/or in triple negative patients (P = 0.05) the development of the brain metastasis was early and the survival after brain metastasis was short. DISCUSSIONS: Since there is a tendency to early brain metastasis in early stage patients with high-grade, lobular/mixed type histology tumors and with a high number of involved lymph nodes, the value of PCI can be explored in these patients by a well designed prospective trial. Advanced stage chemosensitive patients with ErbB-2 over-expression and/or with hepatic metastasis at their first relapse may be candidates for PCI. There is no place for PCI in chemoresistant and triple-negative breast cancer patients.

Effect of adjuvant chemotherapy on integrity of free serum DNA in patients with breast cancer.

It is not known how chemotherapy-induced cell death influences the size distribution of circulating free DNA (cf-DNA) in serum or plasma of cancer patients. In the present study, we investigated the integrity of cf-DNA during adjuvant systemic therapy in patients (n= 41) with invasive breast cancer. Sera taken at the beginning and the end of the adjuvant chemotherapy were comparatively analyzed for the integrity of cf-DNA. The assay was based on quantification of shorter and longer fragments representing apoptotic or non-apoptotic DNA from abundant genomic ALU repeats by quantitative real-time PCR. The ratio of longer to shorter fragments showed the integrity of free serum DNA. During chemotherapy, in half of the patients (51.2%), total DNA levels increased, but decreased in the other half. The distribution of the DNA integrity in the whole patient group after the systemic therapy (median 0.31) did not significantly differ from that at the beginning (median 0.29, P= 0.39). However, in the subgroups, the variation of the DNA integrity was related to the course of the total DNA level. In the subgroup with an increasing DNA level, the median DNA integrity was elevated from 0.27 to 0.39 (P= 0.005), whereas in the group with a decrease it declined from 0.34 to 0.28 (P= 0.044). Our results show that longer fragments released from non-apoptotic cells are the main contributors to increasing DNA levels during adjuvant systemic therapy. This information might be helpful in evaluating the response of patients to adjuvant systemic therapy.

Chemotherapy with pegylated liposomal doxorubicin and cisplatin in recurrent platinum-sensitive epithelial ovarian cancer.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is the only nonplatinum agent to significantly improve survival in patients with platinum-sensitive recurrent ovarian cancer. The present study was designed to assess the efficacy and safety of PLD plus cisplatin combination therapy in these patients. METHODS: Twenty-two women (median age, 57 years) with ovarian cancer that recurred 6 months or more after standard carboplatin and paclitaxel therapy were eligible for enrollment. Cisplatin was administered intravenously as a 60-min infusion on day 1, at a single dose of 60 mg/m(2), and PLD was given intravenously as a 1-h infusion on day 2, at a dose of 50 mg/m(2). Treatment cycles were repeated on an outpatient basis every 28 days. RESULTS: Hematological toxicity was mainly leucopenia/neutropenia, and this was the principal dose-limiting toxicity. Severe (grade III-IV) leucopenia/neutropenia was observed in 7 (32%) and 9 (41%) patients, respectively. Only 2 (9%) patients were complicated by febrile neutropenia. Grade III-IV anemia occurred in only 4 (18%) patients. Severe thrombocytopenia was not noted; only 5 patients (23%) had grade I-II toxicity. NO toxicity in biochemical parameters was noted. Several severe nonhematological adverse effects were managed according to standard protocols and were transient, as well as being well-tolerated. Twenty-one patients were evaluated for response. The overall response rate was 62% (13 of 21; 95% confidence interval [CI], 38%-82%), with four (19%) complete and nine (43%) partial responses. At the time of last follow-up, all of the 22 patients were alive. The median follow-up period was 8.5 months (range, 2 to 22 months). CONCLUSION: PLD combined with cisplatin at the schedule and dosage used in this study is an active and safe second-line chemotherapy regimen with acceptable and easily manageable toxicities in women with platinum-sensitive recurrent ovarian cancer.

Lower level of MAPK expression is associated with anthracycline resistance and decreased survival in patients with hormone receptor negative breast cancer.

INTRODUCTION: Hormone receptor negative breast cancer is encountered in about 30% of all patients with breast cancer and is considered as a prognostically unfavorable subset. The aim of this study is to evaluate the prognostic impact of various molecular markers in patients with receptor negative breast cancer. METHODS: Tumor specimens from 140 patients with receptor negative (ER, PR) breast cancer were analyzed for MAPK, Her-2/neu, EGFR and PI3K expression by immunohistochemistry. The prognostic significance of these molecular factors, in addition to various prognostic variables were determined with respect to disease-free and overall survival. RESULTS: Nineteen (13.6%), 45 (32.1%), 16 (11.4%) and 47 (33.5%) patients had positive staining for EGFR, PI3K, Her-2/neu and MAPK, respectively. Twenty-three patients with positive MAPK (16.4%) had a high level of expression (score 4-7) and 24 (17.1%) had a low score (1-3). A lower percentage of MAPK expression was significantly associated with a poorer OS (p = 0.03) and a tendency for shorter DFS (p = 0.08) among those who were positive for MAPK. Anthracycline resistance remained the only independent significant variable for OS by Cox regression analysis (p = 0.001, HR:26.1). In patients with recurrent disease, median survival after initial relapse was 16.8 months. MAPK was determined as the only prognostic factor for this endpoint. Patients with higher level of MAPK staining showed significantly shorter survival following initial recurrence (p = 0.04). CONCLUSION: MAPK expression is a significant prognostic factor for non-metastatic patients with hormone receptor breast cancer. A lower level of staining is shown to be associated with with antracycline resistance and oveall survival, whereas a higher expression level is correlated with shorter survival following initial relapse, suggesting possible role of different molecular mechanisms pertaining to tumor progression once recurrence occurs. Further translational research is required to elucidate molecular mechanisms of the cross-talk between intracellular signaling and molecular pathways leading to drug resistance in patients with receptor negative breast cancer.

Factors affecting the prognosis of breast cancer patients with brain metastases.

The aim of this retrospective analysis was to investigate the factors affecting the prognosis of brain metastases in breast cancer patients to identify subgroups which might benefit from prophylactic treatments in future. Seventy-three early and 13 advanced stage patients with known Erb-2 status were included. In 14% of the early stage patients, the first recurrence site was isolated brain metastasis. None of the anthracycline resistant patients had brain metastases as their first recurrence site. The median interval between diagnosis and brain metastasis was 41.5 months (95% CI, 35.79-47.20) in early stage patients. The median interval between the first extracerebral metastases to the brain metastases was 15.5 months (95% CI, 12.24-18.76) in all patients. High histologic and nuclear grade, large tumor, anthracycline resistance were the factors which significantly affected the early appearance of brain metastases but only advanced age (> or =55 years, P=.035) correlated with isolated brain metastasis. Progression with isolated brain metastases was significantly higher in responsive ErbB-2 positive population (P=.036) and none of other pathological factors was associated with isolated brain metastasis in advanced stage. The median survival after brain metastasis in patients with brain metastasis as first recurrence was longer than the patients with brain metastasis after other organ metastasis (13 months vs 2 months P=.003). The median survival following brain metastases in complete responsive patients was higher than the others (24 months vs 6 months, P=.002). Therefore, response to systemic treatment was more determinative in the development of isolated brain metastases than clinical and pathologic features. ErbB-2 should be emphasized in prophylactic treatment strategies. Prophylactic cranial radiotherapy may be an effective treatment option for metastatic patients with complete responsive disease and with controlled ErbB-2 positive disease.

A pilot study evaluating the efficacy and toxicity of biweekly gemcitabine and pegylated liposomal doxorubicin in recurrent platinum-resistant epithelial ovarian cancer.

BACKGROUND: Both gemcitabine and pegylated liposomal doxorubicin (PLD) are antineoplastic drugs with clinical activity in patients with platinum-resistant ovarian cancer. The present study was designed to assess the efficacy and safety of biweekly scheduled gemcitabine and PLD combination therapy in such patients. METHODS: Eighteen women with ovarian cancer that had recurred within 6 months after standard carboplatin and paclitaxel therapy were eligible for enrollment. Gemcitabine 2000 mg/m(2) and PLD 20 mg/m(2) were administered intravenously on days 1 and 15 of a 28-day cycle. RESULTS: Hematological toxicity was mild. No severe (grade III/IV) leucopenia/neutropenia or thrombocytopenia was observed. Severe anemia was seen in only 3 (17%) patients. Several other severe nonhematological adverse effects were well tolerated and easily managed. The overall response rate was 28% (5 of 18; 95% confidence interval [CI], 10%-54%) with 2 (11%) complete and 3 (17%) partial responses. The median overall survival time was 17 months (range, 1 to 25 months). The median survival for patients with clinical benefit including disease response or stabilization was 17 months (range, 3 to 26 months) compared to that of patients with progressive disease, which was 2 months (range, 1 to 11 months; P = 0.04). CONCLUSION: A biweekly schedule of gemcitabine combined with PLD is an active and safe chemotherapy regimen with acceptable and easily manageable toxicities in women with recurrent platinum-resistant ovarian cancer.