Imatinib Treatment for Bleomycin-Induced Pulmonary Toxicity.

The basic treatment for bleomycin-induced pulmonary toxicity is corticosteroids. However, unresponsiveness to corticosteroid treatment can be observed in some cases. We present a case of a 51-year-old man, diagnosed with seminoma, who was receiving a combination treatment of bleomycin, etoposide, and cisplatin when admitted to the hospital with progressive cough and exercise-induced dyspnea. The patient's computed thorax tomography imaging showed bilateral consolidation of lungs, bronchoalveolar lavage (BAL) showed neutrophilia, and transbronchial biopsy showed fibroblastic proliferation. The sputum and BAL cultures were all sterile, and the patient was treated with methylprednisolone for the diagnosis of acute interstitial pneumonia. However, despite the corticosteroid treatment, patient suffered a respiratory failure. On the sixteenth day, imatinib 300 mg/day was added to the corticosteroid treatment. The result of the combination therapy was successful; therefore, corticosteroid and imatinib were stopped at the fifth and ninth month of the combination treatment, respectively. The patient, who is still under follow-up without any therapy until now, demonstrated that in cases of bleomycin-induced pulmonary toxicity that is unresponsive to corticosteroids, addition of imatinib to the treatment can be an alternative option.

Prognostic Significance of Adjuvant Chemotherapy Induced Amenorrhea in Luminal A and B Subtypes.

OBJECTIVE: In this retrospective study, chemotherapy induced amenorrhea in patients with early stage breast cancer and its effects on survival were investigated. MATERIALS AND METHODS: Two hundred fifty-two patients received adjuvant chemotherapy without ovarian suppression treatment (OST) from 600 premenopausal patients were included in the study. Patients were divided into two groups; with amenorrhea and without, and compared with clinicopathologic features and survival. SPSS version 17 was used. RESULTS: Chemotherapy-induced amenorrhea (CIA) was observed in 145 (57.5%) of 252 patients who received no OST during follow-up. The 5-year OS rate of patients with CIA was significantly higher than patients without CIA (p= 0.042, 95.9% vs. 89.7% vs. 158.88 vs. 135.33 months, respectively). In the subgroup analysis, the OS in patients with hormone receptor (+) was significantly higher than in those receptor (-) in patients with CIA (p=0.011, 97.5% vs. 90.9% vs. 162.13 vs. 126.16 months, respectively). The OS was significantly longer in the luminal A molecular subtype than in those with luminal B molecular subtype, in patients with CIA, but the difference was not significant in patients without CIA (p=0.027 vs. p=0.074, respectively). CONCLUSION: As a conclusion; survival advantage of the chemotherapy induced amenorrhea more pronounced with hormone receptor positivity, lymph node involvement, and advanced disease over patients who do not develop amenorrhea. This advantage of amenorrhea development further prolongs survival compared with luminal B in the luminal A molecular subtype.

Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients.

AIM OF THE STUDY: Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. MATERIAL AND METHODS: Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. RESULTS: Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12-61) and 19 months (5-45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. CONCLUSIONS: As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients.

Ductal Adenocarcinoma of the Prostate With a Rare Clinical Presentation; Late Gastric Metastasis.

A 67 year male had robotic prostatectomy whose pathology revealed mixed type prostate cancer composed of 55% ductal and 45% acinar components. The patient was then admitted to hospital with sudden health problems including ascites and serious vomiting attacks in the 46th month after prostatectomy and the PSA test was 4565 ng/mL. Gastroscopic biopsy was reported and proved immunhistochemically undifferentiated ductal prostate cancer metastasis. This is the first report of late gastric metastasis of ductal prostate cancer.

A Rare Case of Sunitinib-Induced Hyperammonemic Encephalopathy and Hypothyroidism in Metastatic Renal Cell Carcinoma.

Sunitinib has become a standard treatment agent for metastatic renal cell carcinoma (RCC) for several years. However, various adverse events have been reported. We present a rare adverse effect of hyperammonemic encephalopathy induced by sunitinib. A 66-year-old woman with metastatic RCC referred to the emergency department with confusion that developed 14 days after the initiation of 50 mg/d of sunitinib. Her serum ammonia and thyroid-stimulating hormone levels were markedly elevated (146 µg/dL and 27.27 µIU/mL, respectively). Sunitinib was discontinued, and an enema with lactulose and L-thyroxine were administered. Her mental status and neurologic symptoms were normalized 7 days after the treatment. Serum ammonia level decreased to 61 µg/dL and thyroid stimulating hormone level decreased 22.34 µIU/mL. The incidence of sunitinib-induced hyperammonemia is rarely reported. The relationship between sunitinib and the development of hyperammonemia is not well understood, and the mechanism is unclear. Sunitinib-induced hyperammonemia is very rare, and to the best of our knowledge, this is fourth case hyperammonemia and first case hyperammonemic encephalopathy with hypothyroidism as an adverse effect. Therefore, it is important for clinicians to be aware of hyperammonemia that can occur in several days after the initiation of sunitinib treatment in metastatic RCC.

Is administration of trastuzumab an independent risk factor for developing osteonecrosis of the jaw among metastatic breast cancer patients under zoledronic acid treatment?

One of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect.Our study included 97 patients (mean age: 54 ±â€Š10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients' ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits.Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13-82) and the mean number of ZA infusions was 38 (range: 15-56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively).The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab.

Predictive and prognostic significance of p27, Akt, PTEN and PI3K expression in HER2-positive metastatic breast cancer.

BACKGROUND: The phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway is a key regulator for HER2- overexpressing breast cancer, but data about whether activation of PI3K/Akt is associated with poor prognosis and resistance to trastuzumab therapy is controversial. In this study we investigated predictive and prognostic significance of expression of p27, Akt, PTEN and PI3K, which are components of the PI3K/Akt signaling pathway, in HER2-positive metastatic breast cancer (MBC), retrospectively. MATERIALS AND METHODS: Fifty-four HER2- positive MBC patients who had received first-line trastuzumab-based therapy were recruited for the study group. All of the patient's breast tissue samples were examined for p27 and Akt expression. In addition, twenty-five patients with sufficient amount of tumor tissue were also examined for PTEN and PI3K expression. p27, Akt, PTEN and PI3K were evaluated by immunohistochemistry and their relationship with patient demographic features, tumor characteristics, response to trastuzumab-based treatment and survival outcomes were analyzed. RESULTS: p27, Akt, PTEN and PI3K were positive in 25.9%, 70.4%, 24% and 96% of the cases, respectively. Nomne were significantly associated with response to trastuzumab and time to progression (TTP). A trend toward statistical significance for longer overall survival (OS) was found for PTEN-positive patients (p=0.058); there was no significant relationship between the other immunohistochemical variables and OS. When we analyzed groups regarding co-expression, the PTEN-negative/Akt-negative group had a significantly lower objective response rate (ORR) (20% vs 80%, p=0.023) and the PTEN-negative/p27-negative and PTEN-negative/Akt-negative groups had significantly lower median OS compared to other patients (26.4 months vs 76.1 months, p=0.005 and 25.6 months vs 52.0 months, p=0.007, respectively). CONCLUSIONS: p27, Akt, PTEN and PI3K expression is not statistically significantly associated with ORR, TTP and OS, individually. However, the combined evaluation of p27, Akt and PTEN could be helpful to predict the response to trastuzumab-based therapy and prognosis in HER2-positive MBC.

Vitamin D levels in patients with breast cancer: importance of dressing style.

BACKGROUND: Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer (BC) prevention. It may also be related to prognosis after diagnosis and treatment. The aim of our study was to determine the prevalence of vitamin D deficiency as measured by serum 25-hydroxy vitamin D (25-OHD) levels in patients with BC and to evaluate its correlations with life-style and treatments. MATERIALS AND METHODS: This study included 186 patients with stage 0-III BC treated in our breast center between 2010-2013. The correlation between serum baseline 25-OHD levels and supplement usage, age, menopausal status, diabetes mellitus, usage of bisphosphonates, body-mass index (BMI), season, dressing style, administration of systemic treatments and radiotherapy were investigated. The distribution of serum 25-OHD levels was categorized as deficient (<10ng/ ml), insufficient (10-24 ng/ml), and sufficient (25-80 ng/ml). RESULTS: The median age of the patients was 51 years (range: 27-79 years) and 70% of them had deficient/insufficient 25-OHD levels. On univariate analysis, vitamin D deficiency/insufficiency was more common in patients with none or low dose vitamin D supplementation at the baseline, high BMI (≥25), no bisphosphonate usage, and a conservative dressing style. On multivariate analysis, none or low dose vitamin D supplementation, and decreased sun-exposure due to a conservative dressing style were found as independent factors increasing risk of vitamin D deficiency/insufficiency 28.7 (p=0.002) and 13.4 (p=0.003) fold, respectively. CONCLUSIONS: The prevalence of serum 25-OHD deficiency/insufficiency is high in our BC survivors. Vitamin D status should be routinely evaluated for all women, especially those with a conservative dressing style, as part of regular preventive care, and they should take supplemental vitamin D.

Can megestrol acetate induce thrombosis in advanced oncology patients receiving chemotherapy?

BACKGROUND: Megestrol acetate (MA) is a steroid origin medicine often used for control of cachexia in oncologic palliative care. Thrombosis is a common problem in oncology patients. One question is whether MA can cause thrombosis. This retrospective, registry-based analysis was therefore conducted to assess thrombotic processes in oncology patients using MA concurrent with chemotherapy. MATERIALS AND METHODS: Data on oncology patients at the metastatic stage using MA were obtained from the archives of our center. Outcomes of patients were evaluated for thromboembolic events (VTEs) during treatment. RESULTS: Ninety-seven oncology patients with a median age of 62 (33-84) years were included. During the median follow-up of 17 months, 58 (59.8%) died leaving 39 (31.2%) still alive. Median overall survival (OS) was 19 months (6-180). Mean time of MA use was 8.69 months(±3.53), with a median dose of 160mg (range 160-480mg). Eleven VTEs were detected after MA use, 4 of these in pancreatic cancer cases. The patients with thrombosis non-significantly had worse OS, than those without thrombosis (p=0.106). CONCLUSIONS: This trial revealed that the 11.3% of all patients developed thrombosis,who had been treated with MA and chemotherapy concomittantly. There was no statistically significant difference regarding to occurrence of thrombotic process, among the patients receiving different chemotherapy regimens with MA concomittantly. Pancreatic cancer seemed to be related to thrombosis rather than MA use.