Protective effect of magnesium preloading on cisplatin-induced nephrotoxicity: which dose is more suitable?

OBJECTIVE: Cisplatin is a widely used and potent cytotoxic chemotherapy agent, but its nephrotoxicity is a significant limiting side effect. Various premedication approaches have been implemented to preserve renal function, including magnesium (Mg) preloading. However, the optimal Mg dosage is still unknown. Our study aimed to assess the protective effects of different Mg doses as premedication in cisplatin-based chemoradiotherapy for patients with local/locally advanced cervical and head-neck cancers. PATIENTS AND METHODS: This retrospective, multicenter study involved premedication with saline infusion containing potassium chloride and magnesium sulfate (MgSO4) for all patients before cisplatin treatment. Patients were divided into two groups: 12 mEq MgSO4 (low-dose Mg preload group, low-Mg) and 24 mEq MgSO4 (high-dose Mg preload group, high-Mg). Renal function was evaluated using serum creatinine (sCr, mg/dl) and estimated glomerular filtration rate (eGFR, ml/min). Acute kidney injury (AKI) was defined per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Renal outcomes and efficacy were compared between the groups. RESULTS: In the low-Mg group (n = 159), sCr levels were significantly higher compared to baseline, various weeks during treatment, and at the 1st, 3rd, 6th, and 12th months post-treatment (p < 0.001). In the high-Mg group (n = 128), no significant changes were observed during treatment and at 1st, 3rd, and 12th months post-treatment (p > 0.05). A significant reduction in mean sCr level from baseline to 6 months was noted in the high-Mg group (p < 0.001). eGFR values are generally correlated with sCr levels. AKI occurred in 21 (13.2%) and 22 (17.7%) patients in the low-Mg and high-Mg groups, respectively (p = 0.292). There was no difference in progression-free or overall survival between the groups. CONCLUSIONS: We clearly demonstrated that saline hydration with 24 mEql MgSO4 supplementation before cisplatin treatment has a better renal protective effect than 12 mEql MgSO4 without reducing efficacy, especially in patients with local/local advanced cervical and head-neck cancer receiving cisplatin with concurrent radiotherapy.

A prospectively validated nomogram for predicting the risk of chemotherapy-induced febrile neutropenia: a multicenter study.

PURPOSE: There is clinical need to predict risk of febrile neutropenia before a specific cycle of chemotherapy in cancer patients. METHODS: Data on 3882 chemotherapy cycles in 1089 consecutive patients with lung, breast, and colon cancer from four teaching hospitals were used to construct a predictive model for febrile neutropenia. A final nomogram derived from the multivariate predictive model was prospectively confirmed in a second cohort of 960 consecutive cases and 1444 cycles. RESULTS: The following factors were used to construct the nomogram: previous history of febrile neutropenia, pre-cycle lymphocyte count, type of cancer, cycle of current chemotherapy, and patient age. The predictive model had a concordance index of 0.95 (95 % confidence interval (CI) = 0.91-0.99) in the derivation cohort and 0.85 (95 % CI = 0.80-0.91) in the external validation cohort. A threshold of 15 % for the risk of febrile neutropenia in the derivation cohort was associated with a sensitivity of 0.76 and specificity of 0.98. These figures were 1.00 and 0.49 in the validation cohort if a risk threshold of 50 % was chosen. CONCLUSIONS: This nomogram is helpful in the prediction of febrile neutropenia after chemotherapy in patients with lung, breast, and colon cancer. Usage of this nomogram may help decrease the morbidity and mortality associated with febrile neutropenia and deserves further validation.

Factors predicting lapatinib efficacy in HER-2+ metastatic breast carcinoma: Does it work better in different histologic subtypes?

CONTEXT: Introduction of trastuzumab, a recombinant monoclonal antibody against the extracellular domain of HER-2, is a cornerstone in the treatment of HER-2+ breast carcinoma. However, many cancers that have an initial response to trastuzumab will progress some time later. After progression on trastuzumab-based first-line treatment, there are several options. Although TDM-1 (Trastuzumab emtansine) has prolonged progression-free survival (PFS) and overall survival in patients previously treated with trastuzumab and taxane, it is still not available in Turkey. Patients may be switched to lapatinib (an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2), or they may re-challenge with trastuzumab. There is no clear definition of the patients who should be switched to lapatinib. AIM: In this study, we investigated the factors predicting the efficacy of lapatinib. SUBJECTS AND METHODS: Totally, 94 patients treated with lapatinib for metastatic breast carcinoma was included in our study. Retrospective data including pathology, treatments and treatment results, metastatic sites, and laboratory tests were collected. RESULTS: Progression-free survival was 9.1 months. Histologic subtypes other than invasive ductal carcinoma and liver metastasis were inversely related with PFS. Overall survival was 22.1 months, and patients with histologic subtypes other than invasive ductal carcinoma and who progress with brain metastasis had a worse prognosis. CONCLUSION: Clinicians should give attention to histologic subtype and metastatic sites when choosing patients for lapatinib treatment.

Line of abiraterone acetate in castration-resistant metastatic prostate cancer--Does it matter? report of a multi-institutional experience.

OBJECTIVE: We present our data comparing retrospectively the efficacy of abiraterone and cabazitaxel in patients who progress after docetaxel treatment. PATIENTS AND METHODS: The study included 56 patients diagnosed with hormone-refractory metastatic prostate cancer who were previously treated with abiraterone therapy at four oncology centers in Turkey. RESULTS: With abiraterone, the patients had a median progression-free survival (PFS) of 5.9 months (95% confidence interval (CI) for hazard ratio (HR) (4.4-7.4)) and an overall survival of 13.4 months (95% CI for HR (5.5-21.3)). When we compared the disease-free survival (DFS) of reference patients treated with cabazitaxel as a second-line treatment with those receiving second-line abiraterone therapy, there was no significant difference. (PFS = 5.9 months with cabazitaxel vs. 6.7 months with abiraterone, P = 0.213). CONCLUSION: This study has shown that in our experience abiraterone acetate is an effective agent in metastatic castration-resistant prostate cancer (mCRPC) regardless of the line of treatment.

The effect of small-molecular-weight heparin added to chemotherapy on survival in small-cell lung cancer - A retrospective analysis.

Aims and Background: Small cell lung cancer (SCLC) is a chemotherapy-responsive tumor and associated with alterations in the coagulation system. Addition of low-molecular-weight heparin (LMWH) to combination chemotherapy (CT) had resulted in increase in survival. The present retrospective trial was designed to determine whether the duration of dalteparin usage has an effect on progression and survival. Materials and Methods: The medical records of 67 patients with SCLC who were given cisplatin-etoposide and concomitant LMWH (dalteparin) was evaluated retrospectively. Results: Median follow-up of patients was 11.3 months. Outcome: 10.6% complete response, 3.0% good partial response, 36.4% partial response, 10.6% stable disease, and 39.4% progressive disease. Side-effects were seen in 40.3% of the patients. Median dalteparin duration was 6,1 months. According the duration of dalteparin patients were grouped in three: who took dalteparin less than 4 months (Group A), 4-6 months (Group B) and more than 6 months (Group C). Mean overall survival (OS) in Group A was 6.5 months, in Group B 11.8 months, and Group C 14.6 months. Mean OS in Group B and C were statistically significantly (P < 0.001) longer than Group A, between Group B and C there was not any significant difference (P = 0.037). Mean progression free survival (PFS) was 9 months. Conclusions: The CT plus LMWH minimum 4 months long is well-tolerable, and may improve PFS and OS in patients with SCLC. For treatment of patients with SCLC CT plus LMWH may be considered as effective future-therapy, and further multi-centre randomised prospective clinical trials must be done to determine the new standard treatment approach for SCLC.

Can positron emission tomography-computed tomography predict response in locally advanced rectal cancer patients treated with induction folinic acid and 5-florouracil?

OBJECTIVE: The aim of this study was to determine the pathological complete response rates in a group of locally advanced rectal cancer patients who underwent chemoradiotherapy (CRT) after treatment with induction folinic acid and 5-florouracil (FOLFOX) chemotherapy and the relationship between the complete response and positron emission tomography-computed tomography (PET-CT). MATERIALS AND METHODS: The files of 239 patients who were diagnosed with rectal cancer between January 2008 and January 2012 were evaluated retrospectively. Of these, there were 24 locally advanced rectal cancer patients who met the following criteria: They were administered CRT after receiving four courses induction oxaliplatin, FOLFOX and they underwent PET-CT for staging and for the evaluation of their response to FOLFOX treatment. Of these 24 patients, 20 operable patients were included in the study. RESULTS: The pathological complete response was obtained in seven patients (35%) who were operated on and then given induction four courses FOLFOX chemotherapy and CRT. We determined that age, gender, clinical stage at diagnosis and PET-CT before and after induction chemotherapy were not predictive of the pathological complete response to tumor fluorodeoxyglucose uptake activity. CONCLUSION: The rates of pathological complete response were increased in locally advanced rectal cancer patients who underwent short-term induction chemotherapy. Although the PET-CT has retained its importance in predicting pathological complete response, there is still a need for studies with a larger number of patients and long-term follow-ups.

The importance of COX-2 expression as prognostic factor in early breast cancer.

PURPOSE: A number of studies have been carried out, showing that the risk for breast carcinoma is decreased in those using non-steroidal anti-inflammatory drugs (NSAIDs). Increased cyclooxygenase-2 (COX-2) level is considered as a factor indicating poor prognosis and responsible for angiogenesis, increased cellular proliferation, apoptotic defect and aromatase enzyme induction. For this reason the level of COX-2 might have a prognostic and predictive value in breast cancer as well. This question has become the basis of the present study. METHODS: Eighty-eight female patients with early stage breast cancer being under adjuvant anthracycline based chemotherapy were prospectively recruited. The patient age, body weight, menopausal status, tumor size and grade as well as axillary lymph node involvement were recorded. Routine pathological examination was performed, and COX-2, CerbB2 (HER2), estrogen (ER) and progesterone receptors (PR) levels in breast cancer tissue were determined immunohistochemically. RESULTS: Multivariate analysis confirmed the independent predictive value of both menopausal status and ER expression for overall survival (OS) (p=0.009, HR=1.92, and p=0.014, HR=0.20, respectively). A negative correlation was observed between COX-2 levels and the levels of ER and PR (p=0.006, R= -0.303, and p=0.004, R=-0.312, respectively) whereas no significant correlation was observed concerning CerbB2. No statistically significant correlation was determined between COX-2 levels and the disease-free (DFS) and OS rates. CONCLUSION: Further studies investigating the role of COX- 2 levels in breast cancer progression are needed.

Solitary plasmacytoma: experiences from Central Anatolia.

BACKGROUND: Solitary plasmacytoma localised to bone or soft tissue without myeloma. AIM: Clinical features and survival was analysed in patients from Central Anatolia. METHODS: Twenty-three solitary plasmacytoma (18 male, 5 female) were evaluated retrospectively. Median age was 58 years (46-72). The major localisation was vertebral column. RESULTS: All patients but one (larynx) had surgical resection and 21 patients received radiotherapy postoperatively. Multiple myeloma developed in eight patients (35%) and local relapse was detected in one patient. Eight patients died, causes of death were multiple myeloma progression in six patients, local relapse of intracranial plasmacytoma in one patient and cranial trauma in one patient who was in complete remission. Three and 5 years progression free survival were 45.6% and 22.8% respectively and overall survivals were 54.4% and 27.2% respectively. CONCLUSION: Solitary plasmacytoma cases should be followed carefully regarding local relapse and progression to myeloma.

A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a chemotherapy-responsive tumor type but most patients ultimately experience disease progression. SCLC is associated with alterations in the coagulation system. The present randomized clinical trial (RCT) was designed to determine whether addition of low-molecular-weight heparin (LMWH) to combination chemotherapy (CT) would improve SCLC outcome compared with CT alone. METHODS: Combination CT consisted of cyclophosphamide, epirubicine and vincristine (CEV) given at 3-weekly intervals for six cycles. Eighty-four patients were randomized to receive either CT alone (n = 42) or CT plus LMWH (n = 42). LMWH consisted of dalteparin given at a dose of 5000 U once daily during the 18 weeks of CT. Results Overall tumor response rates were 42.5% with CT alone and 69.2% with CT plus LMWH (P = 0.07). Median progression-free survival was 6.0 months with CT alone and 10.0 months with CT plus LMWH (P = 0.01). Median overall survival was 8.0 months with CT alone and 13.0 months with CT plus LMWH (P = 0.01). Similar improvement in survival with LMWH treatment occurred in patients with both limited and extensive disease stages. The risk of death in the CT + LMWH group relative to that in the CT group was 0.56 (95% confidence interval 0.30, 0.86) (P = 0.012 by log rank test). Toxicity from the experimental treatment was minimal and there were no treatment-related deaths. CONCLUSIONS: These results support the concept that anticoagulants, and particularly LMWH, may improve clinical outcomes in SCLC. Further clinical trials of this relatively non-toxic treatment approach are indicated.

Meropenem +/- granulocyte colony stimulating factor in the treatment of febrile neutropenic patients with cancer: prospective randomized study.

The purpose of this study was to evaluate the impact of granulocyte-colony stimulating factor (G-CSF) on the therapy for febrile neutropenia (FN). Our patient population differed significantly from those of previous studies as no patients received antimicrobial or CSF prophylaxis before randomization and all were solid tumor patients. When the diagnosis of FN was established, patients were started on intravenous meropenem 1 g every 8 hours and randomly assigned to receive G-CSF (5 microg/kg body weight per day subcutaneously) or not. Twenty-eight patients with 30 FN episodes received G-CSF and 25 patients with 30 FN episodes did not receive G-CSF according to randomization. The time to resolution of fever, recovery of neutrophil count over 1000/mm3, duration of hospitalization, need for erythrocyte and platelet transfusion and mortality rate were similar in both study groups. Side effects of therapy were mild. These results provide preliminary evidence that G-CSF administration, in addition to effective antibiotic therapy as treatment of febrile neutropenic patients with solid tumor, does not help improve infection-related morbidity and mortality.

Post-operative sequential chemo-radiotherapy in high-grade cerebral gliomas with fotemustine.

High-grade gliomas are the most common primary brain tumors in adults. Twenty-seven patients with histopathologically proven anaplastic astrocytoma and glioblastoma multiforme were enrolled in this study from November 1998 to August 2002. Radiotherapy was administered after surgery and fotemustine (100 mg/m2) was sequentially administered every 3 weeks for 6 cycles. Overall, 111 cycles were administered to the 27 patients (median, 5 cycles; range, 1 to 6 cycles). Myelosuppression was mild to moderate. The median overall survival and progression free survival were 11+/-3.1 months (95%CI, 4.9-17.1) and 8+/-0.5 months (95%CI 7.1-8.9), respectively. One-year and two-year survivals were calculated at 48% and 7%, respectively. Significant prognostic factors (P<0.05) via univariate analysis were divided into two groups: completion of 6 cycles of chemotherapy versus incompletion of 6 cycles of chemotherapy. This trial demonstrates that postoperative radiotherapy and sequential fotemustine therapy is feasible, well tolerated, and may prolong survival in patients with newly diagnosed high-grade gliomas.

Rapidly relapsing squamous cell carcinoma of the renal pelvis associated with paraneoplastic syndromes of leukocytosis, thrombocytosis and hypercalcemia.

A case history is reported here in which leukocytosis, thrombocytosis and hypercalcemia associated with rapidly relapsing squamous cell carcinoma (SCC) of the renal pelvis were observed. In a 58-year-old man, SCC of the renal pelvis was documented during nephrolithotomy, and right nephrectomy was performed. Local relapse of the tumor occurred rapidly in 2 months' time and hypercalcemia, leukocytosis and thrombocytosis worsened in accordance with tumor volume. Cranial computerized tomography (CT), thorax CT and bone scintigraphy were negative for metastasis. The serum parathyroid hormone level was 28 pg/ml (normal 9- 55 pg/ml). To disclose leukocytosis and thrombocytosis, peripheral smear and bone marrow aspiration were performed and no pathologic finding regarding any hematologic disorder was found; the samples were also BCR-ABL negative and Philadelphia chromosome negative. Production of several factors by tumor cells may be responsible for this paraneoplastic syndrome. The association of SCC of the renal pelvis with this triple paraneoplastic syndrome is an extremely rare occurrence.

Facial nerve paralysis and paraplegia as presenting symptoms of acute myeloid leukemia.

Granulocytic sarcoma is an extramedullary tumor associated with acute or chronic leukemias or myeloproliferative disorders. Rarely, the tumor may be seen before the diagnosis of leukemia. Symptomatic facial nerve paralysis and spinal cord invasion by granulocytic sarcomas are also relatively uncommon. We present here a 17-year-old-female patient who had facial nerve paralysis and paraplegia due to granulocytic sarcoma as the presenting symptoms of acute myeloid leukemia.

Effects of DMSO on platelet functions and P-selectin expression during storage.

Recent studies suggested that the expression of P-Selectin on stored platelets is related to in vitro activation and loss of viability. We examined the effects of dimethylsulfoxide (DMSO) on in vitro function and P-Selectin expression of platelet concentrates. Fresh random-donor platelet units (n = 60) were divided into four equal groups. A DMSO-free group was chosen as a control. DMSO (0.5%, 1.0%, and 3.0%) was added to the other three groups. The samples were stored on a horizontal shaker at room temperature. Biochemical, morphological and platelet function tests and P-Selectin expression were monitored during storage. In all groups, P-Selectin expression, lactate and LDH levels, mean platelet volumes and PO2 increased but the aggregation response to agonist, the recovery response to hypotonic shock, platelet count, glucose level, pCO2, and HCO3 decreased during storage. In DMSO-containing groups, the P-Selectin expression which is a predictor of in vitro activation, was found significantly less often than in the DMSO-free group.

Hodgkin's Disease: Results of a Single Center in Central Anatolia.

Hodgkin's Disease (HD) accounts for about 1% of newly diagnosed malignant diseases. In this study 119 HD cases followed in Erciyes University Hospital were evaluated. 67.2% of the patients was male, 32.8% female. The patients' age ranged from 15 to 72 years with a median of 41.5 years. Of the patients 10.1% was stage I, 29.4% stage II, 39.5% stage III, and 21.0% stage IV. According to Rye classification frequency of histologic subtypes was as follows; 21.0% lymphocyte predominant, 25.2% nodular sclerosis, 43.7% mixed cellularity, and 10.1% lymphocyte depletion. Combination chemotherapy consisting cyclophosphamide, vincristine, procarbazine and prednisolone (COPP) was used as first line treatment in 59.7% of patients. Complete remission was achieved in 84.9% of patients and partial remission in 5.0% of patients; response could not be obtained in remaining 10.1% of patients. Disease progression or recurrence was observed in 30.2% of patients. Five year survival rate was found as 70.8% of all patients, 90.1% for stage I-II, 55.3% for stage III-IV patients (p= 0.03).

An Extra Benefit of Allogeneic Peripheral Blood Stem Cell Transplantation in a Patient with Lymphoblastic Lymphoma: Cure of Thalassemia Minor.

b thalassemia minor is frequent in mediterranean countries. It is a benign disorder and does not warrant any therapeutical intervention. We transplanted a 25-year-old Turkish male who was diagnosed as lymphoblastic lymphoma and had b thalassemia minor as well. He received peripheral blood stem cells transplantation from his HLA-identical sibling who was not a carrier of b thalassemia. After the allogeneic transplantation we did not only observe remission of the lymphoblastic lymphoma but also the disappearance of b thalassemia minor.

A retrospective comparison of allogeneic peripheral blood stem cell and bone marrow transplantation results from a single center: a focus on the incidence of graft-vs.-host disease and relapse.

To detect the effect of the stem cell source, allogeneic peripheral blood stem cell transplantations (alloPBSCTs) performed between 1995 and 1997 from human leukocyte antigen (HLA)-identical siblings in 40 patients with acute and chronic hematological disorders were compared with a historical group of 40 patients with similar variables who had received allogeneic bone marrow transplants (alloBMTs) between 1993 and 1995. Patients in both groups were identical except that both the recipient and the donor ages were, on average, higher in the alloPBSCT group (26 vs. 36 [p = 0.005] and 27 vs. 32 [p = 0.024], respectively). Patients received similar therapy excluding posttransplant granulocyte colony-stimulating factor administration (97% in alloBMT vs. 12.5% in alloPBSCT). The median time to reach neutrophil counts >0.5 x 10(9)/L and platelet counts >20 x 10(9)/L was 13 and 14 days, respectively, in patients receiving alloPBSCTs compared with 19 and 27 days in patients receiving alloBMTs (p = 0.0014 and p = 0.0002). The alloPBSCT group required similar transfusions of red blood cells or platelets. The incidence of grade II-IV acute graft-vs.-host disease (aGVHD) was similar in both groups. However, chronic GVHD (cGVHD) of all grades developed in 78.1% of patients in the alloPBSCT group after a median follow-up period of 12.5 (range 0.5-34) months. In alloBMT recipients, cGVHD of all grades developed in 21.4% after a median follow-up period of 38 (range 0.5-62) months (p = 0.00001). Day 100 transplant-related mortality was also similar: 20% (8 of 40) in the alloBMT patients and 17.5% (7 of 40) in the alloPBSCT group. Although not statistically significant, a relatively higher relapse rate occurred in the alloBMT group (21.4 vs. 10.7%). The estimated disease-free survival in month 24 was 51.3% for alloBMT and 54.6% for alloPBSCT, and the estimated overall survival in month 24 was 56.1% for alloBMT and 64.6% for alloPBSCT. In conclusion, this retrospective comparison suggests that alloPBSCT from HLA-identical donors is associated with faster engraftment, fewer transfusions, and no greater incidence of aGVHD, but a high incidence of cGVHD.