Survival impact of number of removed para-aortic lymph nodes in stage I epithelial ovarian cancer.

PURPOSE: The survival effect of presence or absence of lymphadenectomy in early-stage epithelial ovarian cancer (EOC) was priorly shown but the effect of number of removed lymph nodes kept in background. We aimed to evaluate the survival impact of number of removed lymph nodes and their localizations in stage I EOC. METHODS: This study included 182 patients. The best cut-off levels for number of pelvic and para-aortic lymph nodes (PaLN) were 24 and 10, respectively. Univariate and multivariate survival analyses were performed for these cut-offs and other prognostic factors. RESULTS: The median age of the patients was 49. The median number of removed pelvic and paraartic lymph nodes were 29 and 9, respectively. The median overall (OS) and progression-free survival (PFS) were 67 and 50 months, respectively. The 5-year OS rate was 89.6%. Recurrence occured in 24 (19.5%) patients. In univariate analyses tumor grade (p: 0.005), pelvic LN number (p: 0.041) and PaLN number (p: 0.004) were the factors that were significantly associated with PFS. Tumor grade and PaLN number were independently and significantly associated with PFS in multivariate analyses (p: 0.015 and p: 0.017, respectively). In OS analyses, age, tumor grade, presence of LVI, number of pelvic and PaLNs were the significantly associated factors (p < 0.05 for all). In multivariate analyses, age and PaLN number were independently and significantly associated with OS (p: 0.011 and p: 0.021, respectively). CONCLUSIONS: The number and localizations of removed lymph nodes may have a survival affect in stage I EOC. We also think that this study may constitute a kernel point for larger prospective series on lymph node number and lymphatic regions.

Survival in recurrent ovarian cancer patients before and after the bevacizumab era: an observational single-centre study.

A retrospective observational study was carried out in Baskent University School of Medicine, Ankara, Turkey. Recurrent ovarian cancer patients treated between 2007 and 2017 were divided into two groups according to their bevacizumab status. The primary endpoints were overall survival (OS) and safety. Three hundred and ninety-six patients enrolled in this study, 200 (50.5%) received bevacizumab while 196 (49.5%) patients never received bevacizumab. The median follow-up time was 48.2 and 47.6 months, respectively. The 5-year OS was 61% and 46%, respectively (p=.007). In multivariate analysis, only platinum-sensitivity (HR: 3.75, 95% CI: 3.0-5.32; p<.001) was identified as independent prognostic factors. In subgroup analyses according to platinum status, bevacizumab did not affect the 5 year OS in platinum sensitive patients (64% versus 68% p=.28) but increased survival in platinum resistant patients (36% versus 44%, p=.00). The rate of grade III-IV haematologic toxicities was 13.7% in the bevacizumab group and 11% in the other group (p=.6).Impact StatementWhat is already known on this subject? Bevacizumab increases the progression-free survival in platinum-sensitive and resistant recurrent ovarian cancer patients without changing overall survival.What do the results of this study add? Bevacizumab did not affect OS in platinum sensitive recurrent ovarian cancer patients however improved OS in platinum resistant patients with mild toxicity.What are the implications of these findings for clinical practice and/or further research? This study emphasised the crucial role of bevacizumab in the treatment of recurrent ovarian cancer patients.

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging.

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statementWhat is already known on this subject? The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous.What do the results of this study add? This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups.What are the implications of these findings for clinical practice and/or further research? Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.

Effect of increased number of neoadjuvant chemotherapy cycles on tumor resectability and pathologic response in advanced stage epithelial ovarian cancer.

PURPOSE: To identify the significance of the number of neoadjuvant chemotherapy (NACT) cycles on pathologic response and to define relationship between multiple cycles of NACT and the timing of interval debulking surgery (IDS) in epithelial ovarian cancer (EOC) patients. METHODS: This retrospective case-control study was carried out at the Baskent University in Ankara between 2007 and 2017. We reviewed 62 patients with advanced stage (IIIC-IV) EOC who received NACT in other institutes and operated in our clinic. On the basis of the number of NACT cycles, patients were divided into 2 groups: group 1 received 3 cycles and group 2 received 4 to 6 cycles.The influence of the number of NACT cycles on complete pathologic response, lymph node involvement, overall survival (OS), progression free survival (PFS), platinum resistance and residual tumor were evaluated. RESULTS: The median OS was 44.4 ±4.8 months and 48.8±4.49 months for group 1 and group 2 respectively (p=0.122). PFS was 19.3±3.75 months in group 1 and 24.3±4.67 months in group 2 (p=0.84). Tumor morphology according to lymph node involvement, no visible tumor and complete pathologic response were similar for both groups (p=0.49, p=0.79 and p=0.6 respectively). Pathological absence of residual disease were 13.6% vs 7.5% for group 1 and group 2 respectively (p=0.6) and total response rate was 6/62 (9.67%). Platinum resistance developed in 4 (18.2%) patients and 18(45%) patients in group1 and 2 respectively (p=0.031). Complete resection rates were similar for both groups (p=0.9). After multivariate survival analyses, complete resection remained significant (p=0.000, odds ratio/OR 2.28 [1.41-3.70]), and was independent of age, platinum resistance and number of NACT cycles. Complete resection rates were almost equal in each groups, (68.2% [15/22] and 67.5% [27/40] for group 1 and group 2 respectively (p=0.9)). CONCLUSIONS: Our data suggests that giving more than 3 cycles of NACT is unnecessary because increased number of cycles did not change the resectability and complete pathologic response, while it increased platinum resistance. Moreover OS and PFS remained similar.

The preoperative albumin level is an independent prognostic factor for optimally debulked epithelial ovarian cancer.

PURPOSE: A low albumin level has been reported to be a prognostic factor for various cancers. The aim of this study was to determine the association between preoperative serum albumin level and survival in patients with epithelial ovarian cancer (EOC). METHODS: Records of 337 patients with EOC that underwent optimal cytoreductive surgery were retrospectively reviewed. Threshold albumin level was planned as 32.5 g L-1 due to the statistical analyses. RESULTS: Mean overall survival was 51.5 months. Area under the ROC curve was found statistically significant for the discriminative role of albumin for survival outcome (AUC = 0.857, 95% CI 0.813-0.90, P < 0.001). The best cut-off point for albumin was determined as 32.5 g L-1. The sensitivity rate, specificity rate, positive and negative predictive values, and accuracy rate for this cut-off level were found 67.2, 91.2, 81.2, 83.1, and 82.5%, respectively. Preoperative hypoalbuminemia was noted in 101 (30.0%) of the patients, of which 6.2% had an albumin level <25 g L-1. The albumin level was independently and significantly associated with overall survival (HR 2.6; 95% CI 2.1-3.1; P < 0.001). Subgroup analysis showed that patients with an albumin level <32.5 and ≥32.5 g L-1 had mean estimated overall survival of 40.6 and 96.0 months, respectively. Age, stage, and presence of ascites were the other independent significant factors. CONCLUSIONS: The preoperative albumin level is an independent prognostic factor for overall survival in optimally debulked EOC patients. Further investigations about preoperative albumin level in prognostic models will contribute to the literature.

Response rates of taxane rechallenge in metastatic breast cancer patients previously treated with adjuvant taxanes.

PURPOSE: This study was conducted to determine the efficacy of taxane-based regimens in patients with metastatic breast cancer pre-treated with taxanes in adjuvant treatment and also to assess the response rates of taxanes in each treatment line. METHODS: The data of 939 breast cancer patients, who had received adjuvant taxane-based chemotherapy, were reviewed retrospectively. In 191 of them local/distant recurrences were detected. The treatments that were given when metastases occurred and the responses were recorded. Response rates (RRs), clinical benefit rates/CBR (complete response/CR + partial response/ PR + stable disease/SD) and progression-free (PFS) and overall survival (OS) values were determined. RRs to the most frequently used protocols in our institutes (capecitabine- based and taxane-based regimens) were compared. RESULTS: Of 191 patients, 11 didn't receive treatment and for the remaining 180 patients 45 (24%) received taxane-based therapies, 89 (49.4%) received capecitabine-based therapies, 28 (15.6%) received hormonotherapy and 18 (10%) received other chemotherapeutics. The RR for first-line taxane regimen was 58.5%, consisting of 5 CRs (12%) and 19 PRs (46%). Menopausal status, histological grade, estrogen/ progesterone receptors, cerbB2 status, having PFS > or ? 2 years and the site of metastases did not predict response to first-line taxane treatment. For the 2nd and 3rd or later line therapies, RRs of taxane rechallenge were above 40%. CONCLUSION: Rechallenging with taxanes after (neo)adjuvant taxane exposure seems to be a reasonable option even in 3rd or further line treatments with high response rates.

Effect of surgical staging on 539 patients with borderline ovarian tumors: a Turkish Gynecologic Oncology Group study.

OBJECTIVE: The objectives of this study were to examine demographic and clinicopathologic characteristics and to determine the effects of primary surgery, surgical staging and the extensiveness of staging. METHODS: In a retrospective Turkish multicenter study, 539 patients, from 14 institutions, with borderline ovarian tumors were investigated. Some of the demographic, clinical and surgical characteristics of the cases were evaluated. The effects of type of surgery, surgical staging; complete or incomplete staging on survival rates were calculated by using Kaplan-Meier method. RESULTS: The median age at diagnosis was 40 years (range 15-84) and 71.1% of patients were premenopausal. The most common histologic types were serous and mucinous. Majority of the staged cases were in Stage IA (73.5%). 242 patients underwent conservative surgery. Recurrence rates were significantly higher in conservative surgery group (8.3% vs. 3%). Of all patients in this study, 294 (54.5%) have undergone surgical staging procedures. Of the patients who underwent surgical staging, 228 (77.6%) had comprehensive staging including lymphadenectomy. Appendectomy was performed on 204 (37.8%) of the patients. The median follow-up time was 36 months (range 1-120 months). Five-year survival rate was 100% and median survival time was 120 months. Surgical staging, lymph node sampling or dissection and appendectomy didn't cause any difference on survival. CONCLUSION: Comprehensive surgical staging, lymph node sampling or dissection and appendectomy are not beneficial in borderline ovarian tumors surgical management.

The relationship between glucose metabolism disorders and malignant thyroid disease.

BACKGROUND: Previous studies have shown a positive relationship between insulin resistance and several common adult cancers. The present retrospective study aimed to investigate the association between glucose metabolism disorders (GMDs) and the prevalence of thyroid cancer. METHODS: We investigated the data of 4272 patients who had undergone fine-needle aspiration biopsy (FNAB) of thyroid nodules. The biopsy results were evaluated as diagnostic or non-diagnostic and the diagnostic results were classified as benign, malignant, and indeterminate. In this study, we included 2234 of the above patients who had undergone FNAB at our hospital and whose biopsy results were evaluated as diagnostic and were classified as either benign or malignant. We obtained the cytologic data and the glucose metabolism status of these patients retrospectively. RESULTS: Of the 2234 patients, 629 (28.1 %) had GMD (impaired fasting glucose, impaired glucose tolerance). Malignant cytology was determined in 106 (4.7 %) patients overall. Of the 629 patients with GMD, 582 (92.5 %) patients had benign cytology and 47 (7.5 %) patients had malignant cytology. Fifty-nine (3.7 %) of the 1605 normoglycemic patients had malignant cytology. Malignant cytology was determined more frequently in the patients who had GMDs (p < 0.001). CONCLUSION: The results demonstrated that thyroid cancer prevalence was higher in patients with GMD. According to our results, GMD should be considered as a risk factor for malignancy in the evaluation of thyroid nodules.

Brain metastasis of hepatocellular carcinoma- single center experience.

BACKGROUND: Although the most common intracranial neoplasm in the adult population is metastatic tumors, brain metastasis from hepatocellular carcnoma (HCC) are very rare. The aim of this study is to analyze patients with advanced HCC, in order to determine the incidence of brain metastasis and evaluate the clinicopathologic properties. METHODS: The records of HCC patients treated in our university between 2011 and 2019 were reviewed retrospectively. Patient characteristics, symptoms, laboratory data, treatment modalities, and survival after both the diagnosis of HCC and detection of brain metastasis were recorded. RESULTS: Of the 119 hepatocellular carcinoma patients, 34 had metastasis, 8 of which were to the brain. The median time elapsed between the diagnosis of HCC and brain metastasis was 14.6 months and the median overall survival after the detection of brain metastasis was 1.6 months. In 34 patients with metastasis, median survival was 26.2 months for those without brain metastasis, whereas it was 15.8 months for those with brain metastasis (P = 0.460). The survival times after brain metastasis were 11.6 and 3.9 months for the two patients treated with regorafenib and sorafenib after the detection of brain metastasis, respectively. CONCLUSION: In this study, it was found that patients who were clinically eligible to receive tyrosine kinase inhibitors survived longer after the detection of brain metastasis. Our study shows that multidisciplinary evaluation of these patients is vital for treatment guidance, and survival outcomes can be improved with the advancements in surgical and radiotherapy techniques even in patients with poor prognosis.

Recent Advances in Systemic Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma is typically diagnosed late in its course, and the median survival following diagnosis is short. The recommended therapy for localized hepatocellular carcinoma is surgical resection, but most patients are not eligible because of extensive tumor or underlying liver dysfunction. New treatments and indications for various treatments are evolving rapidly. For patients who are ineligible for liver- directed therapy or for patients showing progression on locoregional therapy, systemic therapy is an option if performance status and underlying liver function are within eligible requirements. Until 2008, no effective therapy existed for patients with advanced-stage hepatocellular carcinoma or for those who did not respond to local therapies. The molecularly targeted agents sorafenib and regorafenib have been shown to improve survival compared with best supportive care alone; a survival benefit has also been shown in the second-line setting for ramucirumab and immune checkpoint inhibitors. Lenvatinib has demonstrated noninferiority to first-line sorafenib. Most recently, the combination of atezolizumab plus bevacizumab was superior to front-line sorafenib. These results have radically changed the treatment landscape for patients with advanced hepatocellular carcinoma.

Solid-Organ Transplantation From Deceased and Living Donors With Cancer or a History of Cancer.

With the introduction of effective screening strategies, cancers are being diagnosed at earlier stages and cumulative survival rates of patients with cancer are increasing. On the other hand, the number of people who would benefit from a solid-organ transplant is also increasing. Continued organ shortages have resulted in evaluations of further potential donors, including patients with cancer. The literature related to donor- derived malignancy transmission is mostly limited to case reports, data registry series, and retrospective studies. According to data from the literature, organs from deceased and living donors with some types of current or past cancers may be safely used for transplant. The risk of cancer transmission must be balanced against the risk of a patient dying or becoming clinically worse during the period of waiting for a transplant on a case-by-case basis. Current transplant protocols are only allowed for patients with central nervous system tumors in Turkey and most other countries. However, some other patients with a history of cancer can be acceptable as organ donors. This review has summarized data from the literature.

Complications of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: An evaluation of 100 cases.

OBJECTIVE: To evaluate the perioperative outcomes and complications of patients with peritoneal carcinomatosis who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This retrospective study included 100 patients operated on between 2016 and 2020. Patients' characteristics, including age, comorbidities, chemotherapy history, treatment failures, cancer type, histology, platinum sensitivity, and perioperative complications, were documented. Perioperative complications were classified according to the Clavien-Dindo classification. RESULTS: Median age was 58 years and median follow-up time was 16 months. Eighty-six (86%) patients had ovarian cancer; 11 (11%) experienced grade III-IV complications, and the only relevant factor was the presence of multiple metastasis (P = 0.031). Seven patients (7%) had surgical-site infection; in multivariant analyses, only ostomy formation was found as an independent risk factor for surgical-site infection (odds ratio [OR] 14.01; 95% confidence interval [CI] 1.36-143.52; P = 0.024). Fifteen (15%) patients experienced elevated serum creatinine after surgery and the median time to creatinine elevation was 5 days postoperatively (range 3-15 days). In multivariant analyses, only age of of 58 years or more was found as a significant factor for the elevation of serum creatinine (OR 6.96; 95% CI 1.42-32.81; P = 0.014). CONCLUSION: Our results showed that the presence of multiple metastases increased the risk of grade III-IV complications and age of 58 years or more was the leading risk factor for renal complications. However, we could not find a relation between postoperative complications and oncologic outcomes. HIPEC seems to be a safe approach in experienced hands.

Emerging drugs in endometrial cancers.

IMPORTANCE OF THE FIELD: Endometrial cancer remains the most common gynecologic malignancy. The treatment of endometrial cancer is rapidly evolving. AREAS COVERED IN THIS REVIEW: In this article, we aim to review current and future treatment options in the medical treatment of endometrial cancers. WHAT THE READER WILL GAIN: The cornerstone of curative therapy for patients with endometrial cancer is surgical treatment. Cytotoxic chemotherapy is the mainstay of therapy for metastatic and advanced endometrial cancer. The most active chemotherapy agents are anthracyclines, platinum compounds and taxanes. Combination chemotherapy has produced higher response rates than single agent therapy. Cisplatin and doxorubicin combination chemotherapy has served as the control arm in many trials. Three-drug combination regimen has shown the highest response rate but with increased toxicity. Despite the lack of published data supporting the superiority of the paclitaxel plus carboplatin combination over doxorubicin and cisplatin, many centers prefer this regimen as a standard of care. Hormonal therapy should be considered in patients with low grade tumors and in those with a poor performance status. Recent advances in the understanding of the molecular biology of endometrial cancer have led to development of targeted therapies. Among these the more promising ones are mTOR inhibitors and antiangiogenic agents. TAKE HOME MESSAGE: Clinical trials are planned to further explore how to best incorporate novel agents into the current treatment algorithm with the aim to improve outcome for women with endometrial adenocarcinomas.

Vismodegib Experience in a Renal Transplant Patient With Basal Cell Carcinoma.

The hedgehog inhibitor vismodegib has been tested and suggested as an effective treatment option for cases of locally advanced or metastatic basal cell carcinoma. A 58-year-old female renal transplant patient with recurrent, inoperable basal-cell carcinoma that originated from nasal skin was evaluated by the transplantation counsel. After a multidisciplinary evaluation of the patient, vismodegib at a dose of 150 mg/day was started in February 2018. Her immunosuppressive regimen consisted of mycophenolate mofetil, tacrolimus, and prednisolone. At her last follow-up in July 2019, she remained disease free with no adverse effects that lowered the quality of life. Although experiences on the use of vismodegib's efficacy and safety have been so far limited and consist of case reports in transplant patients, we experienced an excellent cosmetic result with minimal side effects in a renal transplant patient.

Single-Center Experience of Recurrence Patterns and Survival Analyses of Patients With Hepatocellular Carcinoma and Liver Transplant.

OBJECTIVES: Hepatocellular carcinoma remains a major health problem with increased rates of mortality. The curative treatment options are resection or liver transplant. Because the Milan criteria are restrictive for candidates, they have been expanded into alternative sets of criteria. We aimed to evaluate our indications for liver transplant and their results for hepatocellular carcinoma. MATERIALS AND METHODS: Between December 1988 and January 2020, we performed 652 liver transplant procedures (443 living donors, 209 deceased donors) at Baskent University (Ankara, Turkey). At Baskent University, we developed liver transplant criteria for patients with hepatocellular carcinoma. For our criteria, liver transplant for hepatocellular carcinoma was performed in patients without major vascular invasion and distant metastasis. Clinical data on cancer demographics, recurrence patterns, and survival outcomes were evaluated retrospectively. RESULTS: Of 652 total patients, 49 adult patients (8%) with diagnosis of hepatocellular carcinoma were included in this study. Median age was 55 years. Hepatocellular carcinoma recurrence after liver transplant was detected in 13 patients. Median overall survival was 64.3 months for all study patients; however, median survival was significantly lower in patients who had recurrence (126.3 vs 43.4 mo for nonrecurrent vs recurrent groups; P = .024). In the expanded criteria group (n = 25), 7 patients (28%) had hepatocellular carcinoma recurrence during follow-up, whereas this ratio was 25% (6/24 patients) in the Milan criteria group, with median time to recurrence of 12.6 versus 11.7 months, respectively (not significantly different). CONCLUSIONS: Multidisciplinary treatment modalities, including surgery, interventional radiology techniques, and medical treatments, will probably lead to prolonged survival in patients with hepatocellular carcinoma. According to our center's expanded criteria, recurrence rates and time to recurrence were similar to those shown with the Milan group. We showed that Milan criteria can be safely expanded with promising results even in patients beyond Milan criteria.

Posttransplant Malignancies in Adult Renal and Hepatic Transplant Patients.

OBJECTIVES: The risk of some cancer types increases after organ transplant compared with that shown in the general population; this has been well documented in clinical studies. With patients having longer survival and with the higher number of transplant procedures, cancer is an increasing health concern at high-volume transplant centers. Malignancy has an important effect on short- and long-term graft and patient survival. In this study, we evaluated cancer frequency during transplant patient follow-up. MATERIALS AND METHODS: This single-center retrospective study included patients who underwent solid-organ transplant at the Baskent University Medical Faculty Hospital from 1997 to 2017. Renal and hepatic transplant patients older than 16 years at the time of transplant and diagnosed with cancer after transplant were included the study. In total, 1176 of 2018 renal transplant recipients and 274 of 548 hepatic transplant recipients met the inclusion criteria. RESULTS: We determined that 52 of 1176 renal transplant (4.5%) and 9 of 274 hepatic transplant patients (3.3%) developed posttransplant cancer during follow-up. Of 61 total patients with cancer posttransplant, 44 were males (72.1%) and 17 were females (27.9%), with median age at transplant of 39.2 years. Overall, the incidence of cancer in transplant recipients was 4.2%. The most frequent cancers were basal and squamous skin cancers, which were seen in 18 patients (29%), and Kaposi sarcoma, which was seen in 11 patients (18%). Of the 61 patients who developed cancer, 43 (70%) were still alive at the time of this study. CONCLUSIONS: Despite recent positive developments in the use of immunosuppressive drugs, posttransplant malignancy is still a health problem. Fortunately, most cancers in this patient group have good prognosis and can be cured by surgical resection. Transplant physicians should aim for early detection of these diseases.

SRL172 (killed Mycobacterium vaccae) may augment the efficacy of trastuzumab in metastatic breast cancer patients.

SRL172, non-specific immunological adjuvant downregulates interleukin-4, upregulates interleukin-2 production, switching towards a T-helper-1 response, induces an increase in natural killer cells and activates antigen presenting cells. The human epidermal growth factor receptor 2 gene amplification is frequently observed in a number of primary tumors, suggesting that the overexpression of this growth factor receptor may contribute to transformation and tumorigenesis. Gene amplification occurs in approximately 15-20% of human breast cancers Amplification is associated with aggressive tumor behavior and shortened survival. Trastuzumab, humanized anti-HER-2 antibody targets the HER-2 protein with high affinity. Trastuzumab when used alone or in combination with cytotoxic chemotherapy can induce reasonably durable remissions in a significant percentage of women with metastatic breast cancer whose tumors demonstrate Her-2/neu gene amplification. One of the proposed mechanisms of trastuzumab antitumor action is through antibody dependent cellular cytotoxocity. Pivotal study showed that Trastuzumab+IL-2 resulted in NK cell expansion with enhanced in vitro targeted killing of HER-2-expressing cells. SRL172 by increasing IL-2 production and number of natural killer cells may augment the efficacy of trastuzumab in metastatic breast cancer patients. SRL 172 increases IL-2 production and the number of NK cells in vivo. Based on these data, a clinical trial can be performed to test whether SRL 172 added to trastuzumab is safe and more efficacious.

Selenium supplementation may increase the efficacy of cetuximab in metastatic colorectal cancer patients.

Recently, cyclooxygenase-2 (COX-2) inhibitor therapy has emerged as a possible new approach to the prevention and treatment of colorectal cancer (CRC). The COX enzymes (COX-1 and COX-2) are key enzymes of prostaglandin (PG) biosynthesis and are overexpressed in approximately 80% of human CRCs. Presumably, bioactive lipid products of COX, such as PGE(2), are responsible for some of the pro-neoplastic effects mediated by this enzyme. The early effects of COX-2-derived PGE(2) are in part mediated by the epidermal growth factor receptor (EGFR). Selenomethionine decreases COX-2 protein and PGE(2) levels. Cetuximab is a chimeric IgG1 monoclonal antibody that binds to EGFR with high specificity thus blocking ligand-induced phosphorylation of EGFR. Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory CRC. We suggest that selenium supplementation by decreasing the COX-2 protein and PGE-2 levels in cancer cells may increase efficacy of cetuximab in advanced CRC patients.

Salvage ifosfamide-doxorubicin chemotherapy in patients with recurrent nasopharyngeal carcinoma pretreated with Cisplatin-based chemotherapy.

This study evaluated the efficacy and toxicity of ifosfamide and doxorubicin chemotherapy regimen in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy. Twenty-one patients with recurrent or metastatic NPC previously treated with platinum-based chemotherapy as adjuvant or palliative treatments who received ifosfamide 2500 mg/m(2) d 1-3, mesna 2500 mg/m(2) d 1-3, doxorubicin 60 mg/m(2) d 1, repeated every 21 d was retrospectively analyzed. Patients received a median number of three cycles of ifosfamide-doxorubicin (range: 1-6). Seven patients (33.3%) achieved partial response and no patient achieved complete response. Six (28.5%) had stable disease, whereas three (18.75%) had progressive disease. The median time to progression was 7.0 mo. Ifosfamide-doxorubicin regimen is an effective salvage regimen in patients with recurrent and metastatic NPC.

DNA methylation inhibitor, procainamide, may decrease the tamoxifen resistance by inducing overexpression of the estrogen receptor beta in breast cancer patients.

Estrogen is the main stimulant in the development and growth of breast cancer. The estrogen receptor antagonist tamoxifen has been mainstay of hormonal therapy. Although tamoxifen has been an effective adjuvant therapy, approximately 30% of patients treated with this agent still die within 10 years of follow-up treatment, and relapses can occur for > or = 20 years following therapy. However, the underlying cause of treatment failure in many breast cancer patients receiving tamoxifen is resistance to tamoxifen. ERbeta may influence estrogen action through the ERalpha pathway and the hormone refractoriness of breast cancer. ERbetacx, the carboxy terminal splicing variant of ERbeta, has been considered a dominant repressor of ERalpha function, because ERbetacx inhibits transcriptional activity of ERalpha rather than ERbeta wild type (wt). Tamoxifen responders tended to exhibit a lower ratio of ERbetacx to ERbetawt than non-responders. Induction of ERbeta reduces growth of exponentially proliferating cells. Since the promoter region of ERbeta is rich in CpG dinucleotides, loss of expression of ERbeta observed in some tumours could be due to aberrant methylation of CpG islands. Treatment of ERbeta-negative cell lines with DNA methyl transferase inhibitors restored ERbeta expression, providing experimental evidence that silencing of ERbeta in breast carcinomas could be due to promoter hypermethylation. Procainamide, used for cardiac arrhythmias, has been proposed as being a non-nucleoside inhibitor of DNA methylation and also demthylates and reactivate tumor suppressor genes in breast cancer cell lines. Therefore, concomitant use of procainamide with tamoxifen in ERalpha-positive and ERbeta-negative breast cancers may increase the tamoxifen response. Procainamide, given orally may also be used in breast cancer patients who developed resistance during the tamoxifen treatment. In vivo and in vitro studies evaluating effectiveness of concomitant use of procainamide and tamoxifen in tamoxifen resistant and ERbeta-negative breast cancer may further support our hypothesis.