AT-101 acts as anti-proliferative and hormone suppressive agent in mouse pituitary corticotroph tumor cells.

PURPOSE: Gossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (-)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing's disease still remains a challenge for the clinicians. We aimed to investigate the cytotoxic and apoptotic effects of AT-101 in mouse pituitary corticotroph tumor AtT20 cells. METHODS: Cytotoxic effect of AT-101 was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation and Caspase-3/7 activity. Changes in mRNA expressions of apoptosis-related genes were investigated by qPCR array after treatment with AT-101. ACTH was measured by ACTH-EIA Kit. RESULTS: AT-101 induced cytotoxicity and apoptosis in AtT20 cells. mRNA levels of pro-apoptotic genes such as TNFR-SF-10B, Bid, PYCARD, Caspase-8, Caspase-3, and Caspase-7 were induced by 2.0-, 1.5-, 1.7-, 1.5-, 1.6-, and 2-fold, respectively, in AtT20 cells by AT-101 treatment. Moreover, some of the anti-apoptotic genes such as BCL2L10, NAIP1, and PAK-7 were reduced by 2.1-, 2.3-, 4.0-fold, respectively, in AtT20 cells. AT-101 also decreased ACTH secretion significantly. CONCLUSION: AT-101 induces apoptosis in mouse pituitary corticotroph tumor cells.

Intraperitoneal Administration of Low Dose Aluminium in The Rat: How Good is It to Produce a Model for Alzheimer Disease.

Since neurotoxicity of aluminium (Al) resembles the progressive neurodegeneration observed in Alzheimer Disease (AD), Al administration in several ways has been used to produce AD model. Intraperitoneal (ip) low dose (4.2 mg/ kg) Al injection in rats for long periods is the preferred method by some researchers. In this paper, the efficiency of this method for producing an AD model was evaluated. In this study, we looked at the neuropathology of Al and the characteristic lesions of AD by histological and immunohistochemical techniques and determined oxidative stress markers in the brains of Al-treated and control rats. We also made electrophysiological recordings at the hippocampus and evaluated possible behavioural changes by Morris water maze test. However, no pathologic changes occurred in the animals except for an impairment in long-term potentiation (LTP) in the hippocampus (e.g. the LTPs of population spike (PS) amplitude at 15 min post-tetanus were measured as 217±27% in Al-treated rats and as 240±42% in sham-treated rats, of baseline PS amplitude). According to the findings of the present study, low dose of ip Al in rats is not sufficient to produce a good AD model. Higher doses (≥10 mg/kg) should be used.

Effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in breast cancer patients.

The aim of this study was to explore the effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in patients who completed breast cancer treatment. Sixty breast cancer patients were randomised into three groups, as supervised exercise group, home exercise group and education group. Angiogenesis and apoptosis-related cytokine levels and quality of life (EORTC QOL-C30: European Organisation for Research and Treatment of Cancer Quality of Life C30), fatigue (Brief Fatigue Inventory) and depression (BDI: Beck Depression Inventory) scores were compared before and after a 12-week exercise programme. After the exercise programme, statistically significant decreases were found in interleukin-8 and neutrophil activating protein-78 levels in the home exercise group (P < 0.05). The education group showed a statistically significant increase in monocyte chemoattractant protein-1 level (P < 0.05). Functional score and global health score of EORTC QOL-C30 in the supervised exercise group and functional score of EORTC QOL-C30 in the home exercise group increased significantly after exercise programme (P < 0.05). BDI score was significantly lower in the supervised exercise group after the exercise programme (P < 0.05). Changes in angiogenesis and apoptosis-related molecules in the study groups suggest a possible effect of exercise on these parameters. Exercise programmes are safe and effective on quality of life and depression in breast cancer patients whose treatments are complete.

Sexual dysfunction in cancer patients: a review.

Cancer is a life-threatening disease despite the advanced therapeutic strategies now available. A common problem is that physicians and patients tend to concentrate on intensive medical treatment options and underestimate the treatment-related adverse effects. In this review, we summarize one of these adverse effects in cancer patients; sexual dysfunction (SD). In addition, current therapeutic choices with optimal doses and patient selection strategies are defined. All patients should be informed about problems associated with therapy-related SD and must be guided toward the most appropriate therapeutic options before starting treatment.

Survival analysis of metastatic colorectal cancer patients who were treated with the five major therapeutic agents over the course of disease.

PURPOSE: Exposure to all active agents may be more important than specific sequence of drug administration in the treatment of patients with metastatic colorectal cancer (mCRC). The purpose of this study was to evaluate the overall survival (OS) of mCRC patients who were treated with all 5 major therapeutic agents used in this malignancy. METHODS: We retrospectively reviewed the medical records of 395 mCRC patients referred to our clinic. The study included patients who received 5-fluorouracil (5-FU)-, irinotecan- or oxaliplatin-based chemotherapy and at least 3 cycles of bevacizumab and 4 weeks of cetuximab sequentially in various combinations. RESULTS: Forty mCRC patients received the 5 major therapeutic agents effectively and sequentially, and their mean OS was 26.43±2.04 months. The 3- and 4- year OS survival rates were 26.7% and 16.7%, respectively. When survival analysis was limited to the metastatic patients with at least 6 cycles of bevacizumab therapy in addition to standard duration of other chemotherapeutic agents (N=33), the mean OS was 26.7±2.38 months. With a further survival analysis limited to metastatic patients who were treated with at least both 6 cycles of bevacizumab and 8 weeks of cetuximab in addition to other therapies (N=17), the mean OS was 44.8±11.03 months. CONCLUSION: This study demonstrated that in mCRC patients there may be a significant survival advantage if an adequate tumor response was achieved with all major therapeutic agents. Therefore, we believe that we should treat our patients with the 5 major therapeutic drugs as effectively as possible.

Evaluation of the efficacy of adjuvant chemotherapy in patients with high-risk stage II colon cancer.

PURPOSE: This study aimed at comparing the disease-free survival (DFS) in high-risk TNM stage II colon cancer patients who had been subjected to adjuvant chemotherapy and TNM low-risk stage II patients who did not receive chemotherapy. METHODS: We retrospectively reviewed the medical records of stage II colon cancer patients between January 2006 and December 2011. High-risk patients were defined those with any colonic obstruction/perforation, mucinous histology, inadequate lymph node sampling, T4 disease, lymphatic/ vascular or perineural invasion, preoperatively elevated carcinoembryonic antigen (CEA) and high-grade tumor. All patients with high-risk features received adjuvant chemotherapy. RESULTS: There were 42 patients in the high-risk treatment group and 21 patients in the non-treatment (observation) group. There were no significant differences in terms of gender, tumor size, tumor localization, or the number of excised lymph nodes between the groups. The median follow- up time was 33.9 months in the treatment group and 29.3 months in the non-treatment group. Recurrence developed in 4 patients (6.3%), 3 of which were in the treatment group. DFS in both groups was statistically similar. CONCLUSION: Adjuvant chemotherapy in the high-risk patients resulted in similar DFS as that in the low-risk patients. Although the role of adjuvant chemotherapy for stage II colon cancer is unclear, it is rational to offer adjuvant chemotherapy to patients with high-risk stage II colon cancer.

Alveolar rhabdomyosarcoma originating from the uterine cervix.

Cervical alveolar rhabdomyosarcoma is a rare condition associated with poor prognosis. An 18-year-old patient presented with vaginal bleeding and a protruding mass from the vagina. Biopsy of the mass revealed alveoler rhabdomyosarcoma (ARMS), and radiological evaluation demonstrated that it originated from the uterine cervix. First, Wertheim's operation was carried out followed by four cycles of vincristine, actinomycine-D, ifosfamide (VAI) chemotherapy. However, the disease relapsed within three months, and the patient died of disease progression. Despite combination treatment, we could not achieve a desirable survival advantage in ARMS. Future studies may unveil the genomic profile of this rare condition, leading to invention of targeted therapies, which is the emerging trend in the treatment of sarcomas.

Impaired hypothalamo-pituitary-adrenal axis in patients with ankylosing spondylitis.

BACKGROUND: To investigate the hypothalamic-pituitary- adrenal (HPA) axis in patients with ankylosing spondylitis (AS) and healthy controls. METHODS: Forty-nine AS patients and 20 healthy controls were included. Lowdose ACTH test (LDST) was used to assess the HPA axis. Basal cortisol, stimulated peak cortisol levels, and acutephase reactants [C-reactive protein (CRP), erythrocyte sedimentation rate, and fibrinogen] were studied. Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index were also evaluated. RESULTS: Patient and control groups were not different regarding age, sex, body mass index and waist circumference (WC). Basal cortisol levels did not show a significant difference between groups. However, cortisol increment after low-dose ACTH was significantly impaired in AS subjects with respect to controls (20.0+/-4.4 vs 24+/-2.2 microg/dl, p<0.001). Eleven AS patients had impaired cortisol peak after LDST when a cortisol cut-off is accepted as 500 nmol/l (18 microg/dl) and none of the controls exhibited a peak cortisol responses to LDST<500 nmol/l. Comparison of AS subjects who were receiving anti-tumor necrosis factor (TNF) (no.=23), and conventional therapy (no.=26) yielded similar basal and peak cortisol concentrations. Peak cortisol concentrations were associated with basal cortisol, impaired cortisol response, CRP, and fibrinogen. Impaired cortisol response (subjects with peak cortisol levels <18 microg/dl) was significantly correlated with basal and peak cortisol concentrations and BASDAI. CONCLUSION: Our results indicate an increased prevalence of subclinical glucocorticoid deficiency in AS patients. Anti-TNF treatment seems not to have effect on HPA axis.

Is there any relationship between imatinib mesylate medication and hypothalamic-pituitary-adrenal axis dysfunction?

BACKGROUND: Imatinib mesylate [tyrosine kinase (TK) inhibitor] is a novel medication in the treatment of chronic myelogenous leukaemia (CML). TK is also essential in hypothalamo-pituitary-adrenal (HPA) axis. PURPOSE: The aim of this study was to evaluate HPA axis in patients treated with imatinib. Twenty-five patients were included in this study. METHODS: Glucagon stimulation test (GST) and low-dose (1 microg) adrenocorticotropin test (LDSST) were used to assess the HPA gland axis. RESULTS: Seventeen (68%) subjects had impaired peak response when a cortisol cut-off value is accepted as 500 nmol/L. Twelve (48%) out of 17 subjects also failed to show a response to LDSST. Therefore, 12 patients (48%) were defined as HPA deficient. Only two of these 25 patients had morning serum cortisol < 200 nmol/l (7.22 microg/dl), and failed the GST and/or LDSST, indicating that the majority had partial glucocorticoid deficiency. If the cut-off presume for LDSST is from 500 to 600 nmol/l, 16 patients (64%) would have failed both the GST and LDSST. CONCLUSION: Our results indicate an increased prevalence of subclinical glucocorticoid deficiency in patients receiving imatinib mesylate for CML. Therefore under stressed conditions, such as intercurrent illness state, overt and untreated partial glucocorticoid deficiency in CML patients become life threatening.

Does the tumor localization in advanced pancreatic cancer have an influence on the management of symptoms and pain?

PURPOSE: The symptoms and survival of patients with advanced pancreatic cancer show great variability according to tumor localization. The main purpose of this study was to see for any differences between the intensity of symptoms, mainly pain, and the need for analgesic treatment in advanced pancreatic cancer patients with different (head vs. body-tail) tumor localizations. METHODS: Ninety-six patients with histologically confirmed pancreatic cancer were enrolled in the study. The patients were divided into 2 subgroups according to tumor localization: group 1 (n=50) with head tumors and group 2 (n=46) with body and tail tumors. The demographic features of the patients as well as disease stages, onset of symptoms and necessity and consumption of analgesics were recorded. Patients were followed-up until death, and survival data was also analysed. RESULTS: At the time of diagnosis, patients with body and tail tumors had more advanced disease stages compared to head tumors (p=0.006). While jaundice was the most common initial symptom in head tumors (p<0.0001), it was pain in body and tail tumors (p<0.001). Patients with body and tail tumors had more analgesics consumption as compared to those with head tumors (p=0.009). No statistically significant difference in survival was detected between the 2 groups (p>0.05). CONCLUSION: We believe that pancreatic cancer should be accepted as two diverse disease types according to tumor localization, and pain and symptom management should be organized based on this fact.

Radiosensitization of hormone-refractory prostate cancer cells by gossypol treatment.

PURPOSE: many drugs have been tested to increase the sensitivity of prostate cancer cells to radiotherapy. Gossypol, a natural polyphenolic compound extracted from the cotton plant, is one of the agents the efficacy of which has been investigated in the treatment of prostate cancer for this purpose. The main aim of this study was to investigate the best gossypol application with irradiation, when gossypol was applied either sequentially (24 h before and after irradiation) or concurrently in PC-3 hormone-refractory and radioresistant prostate cancer cells. METHODS: The XTT viability assay was used to evaluate the cytotoxicity of different concentrations of gossypol in PC- 3 cells. Irradiation was applied to PC-3 cells via 6 MV photon linear accelerator and delivered 24 h before, 24 h after radiation or at the same time with gossypol administration. RESULTS: gossypol caused radiosensitization of PC-3 cells that are known to be radioresistant, with high Bcl-2 levels. Among different applications of gossypol and irradiation (before, after and concurrent) in prostate cancer cells, the best results were observed by the application of gossypol 24 h before irradiation. CONCLUSION: our study suggests that gossypol represents a promising novel anticancer treatment for radiosensitization of human hormone-refractory prostate cancer cells.

Screening for metastasis in primary breast cancer patients having four or more axillary lymph node involvement: is it really necessary?

PURPOSE: To evaluate the necessity and direct cost effectiveness of screening and staging procedures in breast cancer patients having ≥4 positive axillary lymph nodes and to identify further possible biopathological risk factors associated with increased risk of metastasis. METHODS: We reviewed the demographic and clinicopathological data from the medical records of 1897 newly diagnosed breast cancer patients. Patients having ≥4 positive axillary lymph nodes after primary surgery for breast cancer and who had staging examinations for metastasis were eligible. The impact of staging procedures (thoracoabdominal CT, bone scan etc.) for detecting metastasis, decision of adjuvant treatment and direct costs were analyzed in 329 patients with operable breast cancer. RESULTS: Thirty-five (10.6%) patients were found with metastasis at diagnosis. Seven (20.0%) among them had multiple metastases. Eighteen (51.4%) had lung, 17 (48.6%) bone, and 7 (20.0%) liver metastasis. Twenty-one (60.0%) patients needed further radiological investigation for metastasis confirmation. Treatment decision was changed in 27 (77.1%) patients. No statistically significant risk factor was identified among the metastatic patients by means of conventional demographic and biopathological parameters. The cost of screening was lower when compared to the cost of treatment without any screening procedure. CONCLUSION: Since the conventional clinicopathological data seems not sufficient to define the risk of developing metastasis in breast cancer patients with ≥4 axillary lymph node involvement, all of them should undergo full staging examinations until new parameters based on genomic level are defined. Staging procedures need modification for high risk breast cancer patients.

Targeting apoptosis in the hormone- and drug-resistant prostate cancer cell line, DU-145, by gossypol/zoledronic acid combination.

Possible synergistic cytotoxic and apoptotic effects of gossypol with zoledronic acid on DU-145 cells were explored, along with the rationale behind any observed synergism due to the different apoptotic proteins involved. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 activity were measured to verify apoptosis. Human Apoptosis Array was used to evaluate apoptotic proteins. The synergistic cytotoxic combination treatment had a versatile effect on apoptotic proteins, through inhibition of anti-apoptotic proteins (including cIAP-1, cIAP-2, survivin, livin, claspin, p53, p21, PON-2 and heat shock proteins) and concurrently the induction of pro-apoptotic proteins (Bad, Bax, Fas, FADD, cleaved caspase-3 and p27). Both drugs had a minimal toxicity profile comparing to cytotoxic agents. Combination treatments targeting many pivotal apoptosis-related proteins may be a rationale option for treatment of prostate cancer.

Docetaxel/zoledronic acid combination triggers apoptosis synergistically through downregulating antiapoptotic Bcl-2 protein level in hormone-refractory prostate cancer cells.

Docetaxel, a semi-synthetic taxane analogue, is used effectively in the treatment of metastatic prostate cancer. Zoledronic acid, the most potent member of bisphosphonates, has shown pleiotropic anti-tumoral effects on prostate cancer cells. We have explored the possible additive/synergistic effects and the apoptotic pathways induced by combination treatment of docetaxel and zoledronic acid in hormone and drug refractory, PC-3 and DU-145 prostate cancer cells. Combination of docetaxel and zoledronic acid synergistically inhibits cell growth in PC-3 and DU-145 cells. Moreover, this effect was due to downregulation of antiapoptotic protein Bcl-2 in PC-3 and DU-145 cells. In conclusion, docetaxel/zoledronic acid combination is potentially a novel and effective approach for the treatment of prostate cancer.

A prudent algorithm for hyperlipoproteinemia in renal transplant recipients.

BACKGROUND: Hyperlipidemia and particularly low-density lipoprotein cholesterol (LDL-C) have been proposed as independent risk factors predisposing to chronic allograft nephropathy. OBJECTIVE: The primary objective of this prospective randomized study was to evaluate the efficacy of the modified National Cholesterol Education Program (NCEP) Step I Diet to prevent posttransplantation hyperlipidemia. The secondary objective was to assess the impact of fluvastatin on the lipid profile of patients unresponsive to dietary measures. METHODS: The study population consisted of 143 consecutive patients who underwent transplantation between October 1998 and January 2005. Patients who failed to demonstrate total and LDL-C levels below the optimal values of 200 mg/dL and 130 mg/dL respectively, were recruited for fluvastatin treatment. The remaining patients who achieved and maintained the target lipid levels continued on the same dietary regimen. RESULTS: Baseline demographic characteristics were not different among the fluvastatin and modified Step I Diet groups. Mean total cholesterol (231.2 vs 187.3 mg/dL; P < .000), LDL-C (134.5 vs 99.2 mg/dL; P < .000), high-density lipoprotein cholesterol (HDL-C; 62.9 vs 55.7 mg/dL; P = .012), and triglyceride (170.3 vs 138.7 mg/dL; P = .011) levels following the dietary run-in period were significantly different between the patients assigned to fluvastatin treatment and those left on the diet, respectively. Fluvastatin achieved reductions ranging from 12% to 14% in the concentrations of total cholesterol (231.2 +/- 4.29 mg/dL to 202.7 +/- 3.89 mg/dL; P < .000) and LDL-C (134.5 +/- 3.53 mg/dL to 115.6 +/- 3.18 mg/dL; P < .000) among 91% of patients after 1 year of treatment. A substantial decrease in all lipoprotein concentrations occurred in 53 patients in the modified Step I Diet group with significant reductions in total cholesterol (187.3 +/- 4.98 mg/dL to 172.7 +/- 3.8 mg/dL; P < .000) and LDL-C (99.2 +/- 4.0 mg/dL to 96.2 +/- 3.44 mg/dL; P < .000). CONCLUSION: Initiation and education of the Step I Diet should be provided during hospitalization. The 3-month dietary run-in period was deemed sufficient to determine the effect of diet on lipid abnormalities. Reduction of lipoprotein levels by a 40-mg daily fluvastatin dose was sufficient, safe, and tolerable.

Enhancement of taxane-induced cytotoxicity and apoptosis by gossypol in human breast cancer cell line MCF-7.

PURPOSE: Gossypol is a natural polyphenolic compound extracted from cotton plant (Gossypium species) which has shown potent inhibitory effect on cell growth of many types of cancers. In this study, we aimed to evaluate the interaction of gossypol with some conventional drugs known to be effective in the treatment of breast cancer, like taxanes, doxorubicin, gemcitabine, cisplatin and vinorelbine, in MCF-7 breast cancer cells. MATERIALS AND METHODS: The XTT viability assay was used to evaluate the cytotoxicity of various cytotoxic agents alone and in combination with gossypol in MCF-7 breast cancer cells. The combination effect analysis of Chou and Talalay was used to identify the most synergistic drug combinations. The possible synergistic effects of the combination of drugs on apoptosis were also evaluated by using two different apoptosis assays. RESULTS: We identified strong synergistic cytotoxic and apoptotic activity of gossypol with taxanes among all other studied cytotoxic drugs. CONCLUSION: This study provides proof that gossypol combined with taxanes may have potential as a novel future treatment for breast cancer.

Impact of calcineurin inhibitors on bone metabolism in primary kidney transplant patients.

OBJECTIVE: Posttransplant bone disease and bone metabolism markers were investigated in primary kidney transplant recipients receiving calcineurin inhibitor (CNI) based triple immunosuppression. We examined the safety profile and independent potential of CNIs on bone formation and bone resorption. The study also attempted to correct for modifiable and nonmodifiable factors that impact on posttransplantation bone metabolism, such as age, renal function, rejection, steroid dosage, and secondary hyperparathyroidism. MATERIALS AND METHODS: Serum alkaline phosphatase and osteocalcin were used as indices of bone formation and urinary deoxypyridinoline as a marker for bone resorption. Bone mineral density (BMD) data were assessed in all patients. Osteocalcin and deoxypyridinoline data were correlated with BMD scores to predict the clinical utility and sensitivity of these tests. Sixty-six patients among 300 kidney transplant recipients were enrolled as eligible candidates based upon more than 12 months' posttransplantation follow-up excellent graft function (GFR values >60 mL/min), and intact parathormone levels <100 pg/mL. RESULTS: Mean follow-up was 1395.3 +/- 179.3 days and 1488.9 +/- 225.1 days for cyclosporine (CsA) and FK506 groups, respectively. Mean values for alkaline phosphatase and osteocalcin were 108.8 +/- 6.0 versus 98.4 +/- 9.7 U/L and 10.1 +/- 1.2 versus 9.8 +/- 1.5 ng/mL for the CsA and FK506 groups, respectively. Both CsA and FK506 caused mild osteoblastic proliferation and matrix mineralization activity, as reflected by increased osteocalcin and alkaline phosphatase levels in 22.6% and 12.5% of patients, respectively. This bone formation activity was counterbalanced by a three-fold increase in urine deoxypyridinoline levels in both groups. Mean deoxypyridinoline levels were, respectively, 13.8 +/- 4.4 versus 11.3 +/- 2.1 nM/mMCr in the CsA and FK506 groups. Thirty-four (68%) patients in the CsA and 10 (62.5%) in the FK506 groups had elevated deoxypyridinoline levels. A strong correlation existed between deoxypyridinoline levels and BMD scores for the CsA group (P < .0001). Despite the presence of relatively greater elevations in deoxypyridinoline and BMD values among CsA-treated patients, there was no significant difference in terms of bone resorption potential of both groups. No correlation existed between iPTH values (<65 pg/mL or among 65 to 98.2 pg/mL) at any time versus osteocalcin, alkaline phosphatase, deoxypyridinoline, or BMD levels. The symptomatic bone disease and fracture rates were 0% in this series. CONCLUSION: Calcineurin inhibitor-based immunosuppression with low maintenance doses of glucocorticoids induces slight bone formation but relatively potent, clinically relevant bone resorption.

Docetaxel and platinum combination chemotherapy in locally advanced or metastatic head and neck cancer.

PURPOSE: To assess the efficacy and toxicity of the docetaxel and platinum combination in patients with locoregionally advanced or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: A total of 24 patients with metastatic or locoregionally advanced SCCHN treated with docetaxel and platinum combination chemotherapy were retrospectively reviewed. All of them had histologically proven SCCHN, measurable disease and ECOG performance status of 2 or less, and were treated with docetaxel 75 mg/m(2) as a 60 min i.v. infusion on day 1, followed by cisplatin 75 mg/m(2) or carboplatin AUC 6 as a 60 min i.v. infusion on day 1 every 3 weeks, until disease progression or unacceptable toxicity. Patients were evaluated for response, survival and toxicity. RESULTS: Seven (29%) patients showed partial response (PR) and 1 (4%) complete response (CR) for an overall response rate of 33%. Twelve (50%) patients had stable disease (SD). Disease control rate was 83%. The median follow-up time was 26.4 months (range 2-127), the median time to progression 16 months (range 2-20), and the median overall survival 19 months (range 2-22). Grade 3-4 hematologic toxicity occurred in 13 (54%) patients. Febrile neutropenia was seen in 5 (21%) patients. CONCLUSION: Docetaxel plus cisplatin or carboplatin is an effective regimen with acceptable safety profile for palliation of locally advanced or metastatic SCCHN.

Pegylated liposomal doxorubicin in heavily pretreated epithelial ovarian cancer patients.

PURPOSE: While most patients with ovarian cancer respond to first-line treatment, 50-75% of these patients will eventually relapse. Pegylated liposomal doxorubicin (PLD) is an active agent indicated for the treatment of patients with disease that is refractory to both paclitaxel- and platinum-based regimens, but skin toxicity remains the dose-limiting toxicity of the drug. The primary objective of this retrospective study was to evaluate the activity and safety of this agent in patients with heavily pretreated ovarian cancer. PATIENTS AND METHODS: Patients with platinum-refractory/ resistant, paclitaxel-pretreated epithelial ovarian carcinoma were treated with PLD 50 mg/m2 in 4-week courses until disease progression or unacceptable toxicity. All patients had progressive disease (PD) before starting PLD. Primary endpoints were response rate, progression free survival (PFS) and toxicity and secondary endpoints duration of response (DOS) and overall survival (OS). RESULTS: Seventeen heavily pretreated patients (median number of previous chemotherapy regimens 3, range 1-5) with taxane- and platinum-refractory disease were analysed. No complete response (CR) was achieved, while 3 (17%) partial responses (PR) and 2 (11%) cases with stable disease (SD) were observed. The median PFS was 15 weeks (range 10-21) and median OS 32 weeks (range 16-47). Palmar plantar erythrodysesthesia (PPE) occurred in 4 (23%) patients and was of grade 4 in 1 (6%) patient. Stomatitis occurred in 3 (17%) patients and was grade 3 in 1 (6%) patient. Grade 3-4 neutropenia occurred in only 2 (12%) patients. No febrile neutropenia was encountered. CONCLUSION: Pegylated liposomal doxorubicin is an active and tolerable agent in heavily pretreated epithelial ovarian cancer patients.

Retrospective analysis of patients with relapsed or refractory testicular nonseminous germ cell tumors treated with autologous stem cell transplantation.

BACKGROUND AND AIM: About 20-25% of the testicular germ cell tumors (TGCT) are relapsed or refractory after first line therapy and optimal treatment for this group is poorly defined. We aimed to analyze the efficacy and safety of autologous stem cell transplantation (ASCT) in this patient group.Material and. METHODS: 19 patients with 28 ASCT were retrospectively analyzed. All the patients were treated with BEP (Bleomycin, etoposide, cisplatin) as first line therapy and TIP(paclitexalifosfamide, cisplatin) was given as salvage chemotherapy. Stem cell collection was performed with TIP and granulocyte stimulating factor. ASCT was performed with carboplatin(700mg/m2) and etoposite(750mg /m 2). The results were provided as median(min-max). P<0.05 was accepted as statistical significant level. RESULTS: After ASCT, complete(CR) and partial remission (PR) rates were 47.3% and 31 .5% respectively. The median overall survival(OS) and progression free survival (PFS) were 18(0-37.4 months) and 7(0-15months) months respectively. Estimated 2-year OS was 47.4% and PFS was 35.3%. Grade 3/4 toxicities including diarrhea, mucositis, and toxic hepatitis were observed in 5 patients. Only one patient died due to complication of transplantation. CONCLUSION: Although the number of the patients in this study is limited, ASCT seems to be a safe and effective treatment modality in relapsed refractory non-seminomatousTGCT with an acceptable OS, PFS and mortality rates.