Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience.

Hypo-fractionated radiotherapy and stereotactic body radiotherapy are viable options for treatment of oligometastases. A prodrug of mitomycin-C is under clinical testing as a pegylated liposomal formulation (Promitil) with an improved safety profile over mitomycin-C. Promitil was offered to two patients with oligometastases from colorectal cancer as radiosensitizer. Each derived durable clinical benefit from Promitil administered immediately prior to and following irradiation. Transient toxicity to normal tissues of moderate to severe degree was observed. Promitil appears to have potential clinical value in this setting. HIGHLIGHTS - Delivery of radio-sensitizing drugs with pegylated (long-circulating) liposomes is a pharmacologically rational approach which remains largely clinically untested.- A mitomycin-c prodrug delivered by pegylated liposomes (Promitil) is activated by thiol groups, which are produced in excess by radiation-damaged cells, thus potentiating the radio-sensitizing effect of Promitil.- Two durable clinical responses in patient with colorectal oligometastases to Promitil and radiotherapy suggest that this approach may be of value in cancer chemo-radiotherapy.

Dexrazoxane added to doxorubicin-based adjuvant chemotherapy of breast cancer: a retrospective cohort study with a comparative analysis of toxicity and survival.

Dexrazoxane is indicated as a cardioprotective agent for patients receiving doxorubicin who are at increased risk for cardiotoxicity. Concerns have been raised on the use of dexrazoxane, particularly in adjuvant therapy, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when dexrazoxane is used. Here, we analyzed retrospectively a cohort of our institute database to assess whether the addition of dexrazoxane causes more bone marrow suppression in breast cancer patients receiving doxorubicin-based adjuvant therapy. The secondary objectives were assessment of the incidence of febrile neutropenia, dose-schedule modifications, recorded cardiac events or cardiac test abnormalities, and overall survival. Eight hundred and twenty-two female patients who received adjuvant (or neoadjuvant) doxorubicin and cyclophosphamide for breast cancer between 2001 and 2013 were included. One hundred and four of these patients also received dexrazoxane concurrently with the adjuvant treatment. Hospital records and, when accessible, community clinic records were reviewed. The median follow-up duration was 7 years for patients receiving dexrazoxane and 7.5 years for patients not receiving dexrazoxane. 85.6% of patients were alive at data lock. Compared with the nondexrazoxane group, patients who received dexrazoxane were older (median age at diagnosis 59 vs. 52 years) and more likely to receive dose-dense AC therapy (73 vs. 59%) and adjuvant trastuzumab treatment (29 vs. 15%). Compared with the nondexrazoxane group, dexrazoxane treatment was associated with a higher rate of hematological side effects: leukopenia (48 vs. 39%), neutropenia (45 vs. 31%, P=0.003), anemia (86 vs. 73%, P=0.005), and thrombocytopenia (37 vs. 22%, P=0.001). There were more febrile neutropenia hospitalizations (20 vs. 10%, P=0.001) and dose reductions (22 vs. 8%, P<0.001) in the dexrazoxane group, but no significant difference in the incidence of treatment delays or cancellations. The incidence of cardiac events was the same in both treatment groups with and without dexrazoxane. There was a nonsignificantly lower mortality rate in the dexrazoxane group (9.6%) compared with the nondexrazoxane group (15.0%) at data lock. Adding dexrazoxane to doxorubicin in adjuvant therapy patients leads to higher rates of bone marrow suppression in all blood components, as well as more febrile neutropenia events, and dose reductions. No differences in events defined as cardiac toxicities were detected. Dexrazoxane had no detrimental effect on survival, despite the higher hematological toxicity, the older median age, and the higher prevalence of HER2-positive disease in the dexrazoxane group.

EGFR mutation testing practice in advanced non-small cell lung cancer.

PURPOSE: Testing tumor samples for the presence of a mutation in the epithelial growth factor receptor (EGFR) gene is recommended for advanced non-squamous non-small cell lung cancer (NSCLC) patients. We aimed to collect data about common practice among Medical Oncologists treating lung cancer patients, regarding EGFR mutation testing in advanced NSCLC patients. METHODS: An internet-based survey was conducted among members of the Israeli Society for Clinical Oncology and Radiotherapy involved in the treatment of lung cancer patients. RESULTS: 24 Oncologists participated in the survey. The participants encompass the Oncologists treating most of the lung cancer patients in Israel. 79% of them use EGFR testing routinely for all advanced NSCLC patients. Opinions were split regarding the preferable biopsy site for EGFR testing material. 60% of participants recommend waiting for EGFR test results prior to initiation of first-line therapy. CONCLUSIONS: EGFR testing is requested in Israel routinely by most treating Oncologists for all advanced NSCLC patients, regardless of histology. In most cases, systemic treatment is deferred until the results of this test are received.

Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: retrospective analysis of a single institution experience.

The aim of the present retrospective study was to evaluate the efficacy and safety of diethylstilbestrol (DES) as treatment for patients with castration-resistant prostate cancer (CRPC) and to identify predicting factors of response to DES. Patients treated with DES during the castration-resistant phase following the failure of prior treatment with LH-RH analogs during the castration-sensitive phase were retrieved from a prostate cancer database of our institution. Patients were treated with a daily dose of DES of 1-4 mg (mean, 2.6 mg) and anticoagulants for thromboembolic prophylaxis until disease progression. We analyzed their medical records, biochemical prostate-specific antigen (PSA) response and time to disease progression (TDP). Disease response and progression were identified according to the PCWG2 criteria. Patient data were examined using Kaplan-Meier survival analysis and statistical correlation tests with intra-patient comparison of the LH-RH and DES treatment phases. Forty-three DES-treated CRPC patients were found in our database through July 2011. The median age was 66 years. Sixty-three percent of the patients achieved a ≥50% decline in their serum PSA levels during DES therapy. Median TDP was 20.4 months for LH-RH analog treatment in the castration-sensitive phase, and 7.1 months for DES treatment in the castration-resistant phase. Durable responses (>1 year) were observed in 31% of the patients. Median overall survival was 57 months from the start of the DES therapy. There was no significant correlation between the TDP under LH-RH analogs and under DES therapy among the 38 patients eligible for correlation analysis. However, the magnitudes of serum PSA responses under DES and LH-RH analogs were significantly correlated with each other, and with the TDP under DES therapy. There were no treatment-related deaths. Four patients (9%) developed thromboembolic complications while under treatment, some of which appeared to be related to a discontinuation of thromboprophylaxis. In conclusion, DES confers substantial clinical benefit in the treatment of CRPC, with a relatively good safety profile when administered with thromboprophylaxis. The use of DES may be effective in CRPC, irrespective of the length of the hormone-sensitive period with LH-RH treatment. The magnitude of PSA response to previous treatment with LH-RH analogs, as well as to DES, was predictive of the duration of response to DES.

Cost-effectiveness of baseline low-dose computed tomography screening for lung cancer: the Israeli experience.

OBJECTIVE: Reduced mortality with low-dose computed tomography (LDCT) lung cancer screening was demonstrated in a large randomized controlled study of high-risk individuals. Cost-effectiveness must be assessed before routine LDCT screening is considered. We aimed to evaluate the cost-effectiveness of LDCT lung cancer screening in Israel. METHODS: A decision analytic framework was used to evaluate the decision to screen or not screen from the health system perspective. The screening arm included 842 moderate-to-heavy smokers aged 45 years or older, screened at Hadassah-Hebrew University Medical Center from 1998 to 2004. In the usual-care arm, stage distribution and stage-specific life expectancy were obtained from the Israel National Cancer Registry data for 1994 to 2006. Lifetime stage-specific costs were estimated from medical records of patients diagnosed and treated at Hadassah Medical Center in the period 2003 to 2004. The analysis considered possible biases-lead time, overdiagnosis, and self-selection. Cost per quality-adjusted-life-year (QALY) gained by screening was estimated. RESULTS: Base-case incremental cost per QALY gained was $1464 (2011 prices). Extensive sensitivity analysis affirmed the low cost per QALY gained. The cost per QALY gained is lower than $10,000 with probability 0.937 and is lower than $20,000 with probability 0.978. CONCLUSIONS: Our analysis suggests that baseline LDCT lung cancer screening in Israel presents a good value for the money and should be considered for inclusion in the National List of Health Services financed publicly.

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme.

Fulvestrant ("Faslodex") is a new oestrogen receptor (ER) antagonist with no agonist effects that is licensed in the USA, Brazil, Europe and elsewhere for the treatment of advanced breast cancer (ABC) in postmenopausal women following progression on other endocrine agents. This report consolidates clinical experience from the "Faslodex" Compassionate Use Programme, including a total of 339 patients treated at eight cancer centres. Patients received fulvestrant as first- (n=22), second- (n=125), third- (n=105), fourth- (n=58), fifth- (n=22) or sixth-line (n=5) hormonal treatment for ABC, with two patients receiving fulvestrant after more than six other endocrine therapies. Objective response was achieved by 40 patients and stable disease lasting 6 months by 92 patients, giving overall clinical benefit (CB) in 132/339 patients (39%). The CB rate decreased as fulvestrant was used later in the sequence of endocrine treatments, from 46% (10/22) with first-line fulvestrant to 27% (6/22) with fifth-line fulvestrant. Increased benefit was found in patients with tumours expressing both ER and progesterone receptor (PgR) compared with other combinations, although good activity was reported in patients expressing either ER or PgR as well as in tumours expressing human epidermal growth factor receptor 2. Fulvestrant was well tolerated; adverse events were noted in 18/339 patients (5%). These findings concur with data from the clinical-trial setting and further support the assertion that greater benefit is derived when fulvestrant is used early in the treatment sequence.

The cancer pain experience of Israeli and American patients 65 years and older.

With the aging of the world's population, cancer pain will become an increasingly important health issue. The purpose of this study was to describe the cancer pain experience of Americans (n = 60) and Israelis (n = 39) 65 years and older. Outpatients in teaching hospitals in the U.S. and in Israel completed study questionnaires. Thirty percent of the total variance of worst pain was explained by age, symptom severity, and cancer stage, and 40% of the total variance of pain interference was explained by whether they were American or Israeli, symptom severity, and sense of coherence. Israeli patients had significantly higher scores on worst pain and pain interference, and significantly lower pain management index (PMI) and knowledge and attitudes toward pain and pain control scores. Studies with larger samples and across different cultures are needed to confirm these findings in order to develop culturally appropriate interventions.

The cancer pain experience of Israeli adults 65 years and older: the influence of pain interference, symptom severity, and knowledge and attitudes on pain and pain control.

GOALS: Little is known about Israeli elders' cancer pain experience. The purpose of this study was to explore the cancer pain experience, including pain intensity, pain management index, pain interference, symptom severity, and knowledge and attitudes toward pain and pain control. PATIENTS AND METHODS: Descriptive cross-sectional methods were used to obtain data with four instruments. The patients were 39 Israelis 65 years and older who were receiving outpatient treatment for cancer in a major hospital center in Israel. RESULTS: Results showed that over half (56.7%) reported severe worst pain and had negative pain management indexes (56.4%). In addition, knowledge and attitudes toward pain and pain control were poor (54.55%). There were no significant relationships between pain intensity and other variables. However, pain interference demonstrated a significant positive relationship with symptom severity. Post hoc analysis revealed that Ashkenazi Jewish and more educated patients reported significantly less pain interference than Sephardic Jewish patients. CONCLUSION: Larger samples representative of the cultural differences in Israel are needed to more definitively identify elements of the cancer pain experience in Israeli elders that can be addressed to improve pain management.

Clinical outcomes of surgical resections for primary liver sarcoma in adults: results from a single centre.

BACKGROUND: Primary hepatic sarcoma is a rare tumour with a poor prognosis. METHODS: From 1997 to 2002 eight patients had liver resection for primary sarcoma of the liver at our institution. The clinical characteristics, imaging findings, surgical procedures, adjuvant therapy and outcome were retrospectively reviewed. There were two patients each with angiosarcoma (AS), leiomyosarcoma (LMS), and undifferentiated embryonal sarcoma (UES), one patient with epithelioid hemangioendothelioma (EHE) and one patient with malignant peripheral nerve sheath sarcoma (PNSS). RESULTS: The most common presenting symptoms were right upper quadrant pain and fever. Typical imaging findings were a heterogenous mass with poorly defined margins, pseudocapsule and aberrant vasculature. Preoperative diagnosis of a primary liver sarcoma was made in 7/8 cases, either by fine needle aspiration (n = 5) or angiography (n = 2). Five right hepatectomies and three trisegmentectomies were performed. An R (0) resection was possible in three cases. Two patients developed complications and there was one death. Adjuvant chemoradiotherapy was administered to 5/7 patients. Systemic chemotherapy led to tumour regression in both patients with UES which enabled a second hepatic resection. CONCLUSIONS: The majority of patients with primary liver sarcoma present with right upper quadrant pain, fever and a liver mass. Differentiating the rare primary liver sarcoma from the much more common hepatocellular carcinoma (HCC) may aid in planning therapy. Patients with resectable tumours should be referred for surgery. Liver resection combined with adjuvant chemotherapy are the mainstays of treatment for UES in the adult.