Radiotherapy RSS : Gourt

Permanent Oncology Job in Long Beach California with Long Beach Memorial Medical Center

Seeking a Board-Certified Breast Medical Oncologist who will provide medical direction, coordination and oversight for a leading, hospital-based Southern California breast center. The incumbent will

Permanent Oncology Job in Southeast Kansas with Rural Health Education & Services

Medical Oncologist to join busy multi-specialty group. The 190-bed admitting hospital provides full service general acute care including CT, ER, home health, hospice, ICU, MRI, nuclear medicine, ultrasound,

Permanent Oncology Job in Yuma Arizona with Yuma Regional Medical Center

Outstanding opportunity for an oncologist seeking quality of medicine and quality of life. Seeking BC/BE Oncologist to join a well established and well respected medical oncology practice in the desert

Permanent Oncology Job in Riverton Wyoming with Riverton Memorial Hospital

Seeking hematologist/oncologist for busy oncology clinic. Associated with hospital on campus. Full package available. Beautiful country. Outdoor activities. No pollution or traffic. No managed care or

Permanent Oncology Job in Not Disclosed Ohio with Locum Medical Group

A small, single specialty group of Hematologists and Oncologists are searching for a third Board Certified or Board Eligible Hem/Onc to join their group. Their practice is located approximately 1 hour

Permanent Oncology Job in Northern California with Medical Search International

I have a great permanent Oncology position in Northern California. We have a client that has indicated that they are going to be recruiting in the next couple of months to replace one of their Medical

Locum to Permanent Oncology Job in Call for More Information Minnesota with Medical Search International

We have a wonderful job just for you. If you are interested in making lots of money and working in a great setting with great people we want to talk with you. This need is starting ASAP and this will

Locum to Permanent Oncology Job in Call for More Information Minnesota with Medical Search International

Oncology Need in Minnesota This is a great opportunity to make great $$$. This client is recruiting perm but until they find the right candidate they are willing to use Locums. This means that you

Permanent Oncology Job in Call for More Information Pennsylvania with Medical Search International

Wonderful opportunity in the greater Harrisburg area for a BC/BE Medical Oncologist. State license is preferred but eligibility is acceptable. Residents and fellows are welcomed!! Excellent support

Permanent Oncology Job in Call for More Information Texas with Medical Search International

A busy Medical Center in the Dallas/Ft. Worth metroplex is seeking a BC/BE Radiation Oncologist. The office equipment includes a Linear Accelerator and a PET CT. State license eligibility is acceptable.

Permanent Oncology Job in Excellent Location New York with Spot On Recruiting

Hem/Onc needed 60 miles from Syracuse, NY: No Visa's. this group is seeking a BC/BE Hem/Onc. Their Hematologist/Oncologist performs consultations in a state of the art central office and serves as a consultant

Permanent Oncology Job in Excellent Location Virginia with Spot On Recruiting

Med/Onc needed in Southwest Virginia minutes from Kingsport, TN: No visa's. Hospital currently has opportunities for BC/BE Medical Oncologist or Hematology/Oncology Physician to join their team of physicians.

Permanent Oncology Job in Excellent Location Mississippi with Spot On Recruiting

Hem/Onc needed in Hattiesburg, MS area: Join a well established, very busy traditional in and out patient practice. A well respected Cancer Center in the community. Facility: - JCAHO accredited

Locum Tenens Oncology Job in North Dakota facility seeks Medical Oncology coverage North Dakota with

Job 9580980-0031 Med Onc locums physician needed to provide coverage for staff summer vacation. Candidate must have active North Dakota license. Experienced and highly professional support staff Call

Locum Tenens Oncology Job in Medical center in South Carolina seeks Medical Oncologist South Carolina with

Job 9503632-0015 Solo practice seeks locums Med Onc to provide coverage for staff summer vacation. Physician must be Board Certified and have active SC license. Flexible dates Inpatient and Outpatient

Locum Tenens Oncology Job in New Hampshire facility seeks Medical Oncologist New Hampshire with

Job 9585415-0005 Hospital based group seeks locums Med Onc physician to provide coverage. Need is for the beginning of July through early fall. Ideal candidate will be available 3 days per week.

Locum Tenens Oncology Job in Care center seeks Medical Oncology coverage in Indiana Indiana with Weatherby Locums

Job 9581990-0003 Free standing center seeks Med Onc physician to provide locums vacation coverage. Internal Medicine and Vascular Access Devices. Board Certification required Monday - Friday 9 am -

Permanent Oncology Job in Lake Havasu City Arizona with California Physician Opportunities

LH-1015 Lake Havasu City, "America's Home for the London Bridge", A Mecca of outdoor recreation, ideal climate, captivating scenery, beautiful yet rugged mountains, tranquil desert plus

Locum Tenens Oncology Job in Hospital in Maryland seeks Medical Oncology coverage Maryland with Weatherby Locums

Job 9507006-0026 Facility is currently looking for locums physician to provide Medical Oncology coverage. Physician must be Board Certified and will be responsible for both inpatient and outpatient cases.

Locum Tenens Oncology Job in Washington state facility seeks Medical Oncology coverage Washington with Weatherby Locums

Job 9603259-0001 Clinic seeks Board Certified locums medical oncology physician to provide additional coverage. Physician will see all adult population made up of 14 - 16 patients per day. Ideal candidate

in this issue

The use of sedation to relieve cancer patients' suffering at the end of life: addressing critical issues

What is the role of chemotherapy in estrogen receptor-positive, advanced breast cancer?

Most breast tumors depend on female sex hormones for development and growth, thus being amenable to endocrine therapies. In the management of estrogen receptor (ER)-positive, advanced breast cancer, conventional wisdom dictates the use of endocrine therapy for patients with good prognostic features, whereas chemotherapy is recommended for the treatment of visceral crisis. There is, however, considerable uncertainty regarding the best initial strategy for patients with poor prognostic features other than visceral crisis, such as small-volume visceral involvement and a short disease-free interval after adjuvant therapy. In this article, we examine the role of chemotherapy in ER-positive, advanced breast cancer. Our review of the literature suggests that, in the absence of visceral crisis, endocrine agents should always be considered a major option for the initial treatment of ER-positive, metastatic breast cancer due to their proven efficacy and favorable toxicity profile. Although certain chemotherapy agents can induce higher response rates and more rapid responses, which are desirable effects in particular situations, the up-front use of chemotherapy does not seem to influence the overall outcome of the disease. In the subset of patients with epidermal growth factor type 2-positive disease, on the other hand, current data still do not support the use of endocrine agents alone.

Palliative sedation therapy does not hasten death: results from a prospective multicenter study

Background: Palliative sedation therapy (PST) is indicated for and used to control refractory symptoms in cancer patients undergoing palliative care. We aimed to evaluate whether PST has a detrimental effect on survival in terminally ill patients. Methods: This multicenter, observational, prospective, nonrandomized population-based study evaluated overall survival in two cohorts of hospice patients, one submitted to palliative sedation (A) and the other managed as per routine hospice practice (B). Cohorts were matched for age class, gender, reason for hospice admission, and Karnofsky performance status. Results: Of the 518 patients enrolled, 267 formed cohort A and 251 cohort B. In total, 25.1% of patients admitted to the participating hospices received PST. Mean and median duration of sedation was 4 (standard deviation 6.0) and 2 days (range 0–43), respectively. Median survival of arm A was 12 days [90% confidence interval (CI) 10–14], while that of arm B was 9 days (90% CI 8–10) (log rank = 0.95, P = 0.330) (unadjusted hazard ratio = 0.92, 90% CI 0.80–1.06). Conclusion: PST does not shorten life when used to relieve refractory symptoms and does not need the doctrine of double effect to justify its use from an ethical point of view.

Comprehensive clinical follow-up of late effects in childhood cancer survivors shows the need for early and well-timed intervention

Background: Due to recent advances in treatment, nearly 80% of childhood cancer patients become long-term survivors. Studies on the late effects of survivors are under way worldwide. However, data on Asian survivors remain limited. Methods: Data on 241 survivors at the Long-term Follow-up Clinic in Severance Hospital, South Korea, were collected and late effects were confirmed by oncologists. Results: The median follow-up from diagnosis was 7.8 years. Late effects were identified in 59.8% of survivors and 23.2% had two or more late effects. Grade 3 or higher late effects were present in 10.8%. The most common late effects involved endocrine system (29.0%). Late effects were present in 95.7% of brain tumor survivors and 36.0% of Wilms' tumor survivors. Chemotherapy, hematopoietic stem-cell transplantation and radiotherapy were significant factors associated with the number and severity of late effects (P < 0.05). Brain tumor survivors had more severe late effects (P < 0.001), whereas Wilms' tumor survivors had fewer and milder late effects (P < 0.05). Conclusion: The observation that over 50% of cancer survivors suffered from late effects during the short follow-up period and that a high frequency of endocrine late effects was present indicates the need for early and well-timed intervention of the survivors.

A risk score to predict disease-free survival in patients not achieving a pathological complete remission after preoperative chemotherapy for breast cancer

Background: We aimed to predict disease-free survival (DFS) in patients who failed to achieve a pathologic complete remission (pCR) after preoperative chemotherapy (PC). Patients and methods: Data from 577 patients treated with PC and operated at the European Institute of Oncology (EIO) were used to develop a nomogram using Cox proportional hazards regression model based on both categorical (pT, positive nodes, human epidermal growth factor receptor 2 (HER2) status, vascular invasion) and continuous histological variables (estrogen receptors and Ki-67 expression) at surgery. The nomogram was tested on a second patient cohort (343 patients) treated in other institutions and subsequently operated at the EIO. Results: The nomogram for DFS based on both categorical and continuous variables had good discrimination in the training and the validation sets (concordance indices 0.73, 0.67). Conclusion: The use of a nomogram based on the degree of selected histopathological variables can predict DFS and might help in the adjuvant therapeutic algorithm design.

Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative large operable breast cancer

Background: Findings from our previously published phase II study showed a high pathologic complete remission (pCR) rate in patients with triple-negative large operable breast cancer after the administration of eight cisplatin–epirubicin–paclitaxel (PET) weekly cycles. The safety and efficacy data of the initial population were updated, with inclusion of additional experience with the same therapy. Methods: Patients with triple-negative large operable breast cancer (T2–T3 N0–1; T > 3 cm) received eight preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2, paclitaxel (Taxol) 120 mg/m2, with granulocyte colony-stimulating factor (5 µg/kg days 3–5) support. Results: Overall 74 consecutive patients (T2/T3 = 35/39; N0/N+ = 26/48) were treated, from May 1999 to May 2008. At pathological assessment, 46 women (62%; 95% confidence interval 50–73) showed pCR in both breast and axilla. At a 41-month median follow-up (range 3–119), 13 events (nine distant metastases) had occurred, 5-year projected disease-free survival (DFS) and distant disease-free survival being 76% and 84%, respectively. Five-year DFS was 90% and 56% in pCRs and non-pCRs, respectively. Severe neutropenia and anemia occurred in 23 (31%) and eight (10.8%) patients, respectively. Severe non-hematological toxicity was recorded in <20% of patients. Peripheral neuropathy was quite frequent but never severe. Conclusions: Eight weekly PET cycles are a highly effective primary treatment in women with triple-negative large operable breast cancer. This approach results in a very promising long-term DFS in this poor prognosis population. This triplet regimen is worthy of evaluation in phase III trials.

A prognostic model based on nodal status and Ki-67 predicts the risk of recurrence and death in breast cancer patients with residual disease after preoperative chemotherapy

Background: Preoperative chemotherapy (PCT) allows for in vivo testing of treatment effects on tumor and its microenvironment. Aim of this analysis was to evaluate the effect of PCT on tumor biomarker expression and to evaluate the prognostic role of treatment-induced variation of these biomarkers (molecular response). Methods: Two hundred and twenty-one stage II–III breast cancer patients were included. The following parameters were evaluated at baseline and on surgical specimens after PCT: estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, human epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR2), and apoptosis. Results: A pathological complete response was observed in 8.8% of the patients. PCT induced a significant reduction in the expression of ER, PgR, Ki-67, and apoptosis. As by multivariable model, Ki-67 ≥15% and nodal positivity after preoperative chemotherapy (PCT) were significant predictors of worse disease-free survival [hazard ratio (HR) 3.79, P < 0.0001 and HR 2.31, P = 0.037, respectively]. Ki-67 ≥15% after PCT was also a significant predictor of overall survival (HR 3.75, P = 0.013). On the basis of these two parameters, patients were classified into three groups: (i) low risk (negative nodes and Ki-67 <15%), (ii) intermediate risk (nodal positivity or Ki-67 ≥15%), and (iii) high risk (nodal positivity and Ki-67 ≥15%). As compared with the low-risk group, the HRs for recurrence were 3.1 and 9.3 for the intermediate- and high-risk group, respectively (P = 0.0001); the HRs for death were 2.4 and 6.5 for the intermediate- and high-risk group, respectively (P = 0.042). Conclusions: Ki-67 and nodal status have been used to generate a simple and easily reproducible prognostic model, able to discriminate patients with worse prognosis among the heterogeneous group of women with residual disease after PCT.

Effectiveness of organised versus opportunistic mammography screening

Background: Detailed comparison of effectiveness between organised and opportunistic mammography screening operating in the same country has seldom been carried out. Patients and methods: Prognostic indicators, as defined in the European Guidelines, were used to evaluate screening effectiveness in Switzerland. Matching of screening programmes’ records with population-based cancer registries enabled to compare indicators of effectiveness by screening and detection modality (organised versus opportunistic screening, unscreened, interval cancers). Comparisons of prognostic profile were also drawn with two Swiss regions uncovered by service screening of low and high prevalence of opportunistic screening, respectively. Results: Opportunistic and organised screening yielded overall little difference in prognostic profile. Both screening types led to substantial stage shifting. Breast cancer prognostic indicators were systematically more favourable in Swiss regions covered by a programme. In regions without a screening programme, the higher the prevalence of opportunistic screening, the better was the prognostic profile. Conclusions: Organised screening appeared as effective as opportunistic screening. Mammography screening has strongly influenced the stage distribution of breast cancer in Switzerland, and a favourable impact on mortality is anticipated. Extension of organised mammography screening to the whole of Switzerland can be expected to further improve breast cancer prognosis in a cost-effective way.

Effects of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German, 12-month, prospective, randomised substudy

Background: Adjuvant treatment of hormone receptor-positive breast cancer in postmenopausal women with aromatase inhibitors may be associated with increased bone loss. Patients and methods: Two hundred patients were randomised to receive exemestane or tamoxifen as adjuvant treatment of hormone receptor-positive breast cancer. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry at baseline and after 6 and 12 months treatment. Results: One hundred and sixty-one patients were assessable. Tamoxifen treatment resulted in a 0.5% increase from baseline in BMD at the spine, which was maintained at 12 months. Exemestane-treated patients experienced a 2.6% decrease from baseline in BMD at the spine at 6 months and a further 0.2% decrease at 12 months. There were significant differences in the changes in BMD between tamoxifen and exemestane at 6 and 12 months (P = 0.0026 and P = 0.0008, respectively). The mean changes in BMD from baseline at the total hip were also significantly different between exemestane and tamoxifen at 6 and 12 months (P = 0.0009 and P = 0.04, respectively). There was no difference between tamoxifen and exemestane in mean changes in BMD from baseline at the femoral neck. Conclusions: Exemestane treatment resulted in an increase in bone loss at 6 months; bone loss stabilised after 6- to 12-month treatment.

Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel, and alternating AC and docetaxel as front-line chemotherapy for metastatic breast cancer: Japan Clinical Oncology Group trial (JCOG9802)

Background: This randomized, multicenter, phase III trial compared doxorubicin plus cyclophosphamide (AC), single-agent docetaxel (D), and an alternating regimen of AC and docetaxel (AC–D) as first-line chemotherapy in metastatic breast cancer (MBC). Patients and methods: Patients with MBC resistant to endocrine therapy were entered in a randomized study to receive either six cycles of AC (doxorubicin 40 mg/m2 plus cyclophosphamide 500 mg/m2), D (60 mg/m2), or alternating treatment with AC–D (i.e. three cycles of AC and three cycles of D). Treatment was administered every 3 weeks. Results: A total of 441 patients were entered in a randomized study. Response rates were 30% for AC, 41% for D, and 35% for AC–D. The median times to treatment failure (TTFs) were 6.4, 6.4, and 6.7 months (one-sided log-rank test, P = 0.13 for AC versus D, P = 0.14 for AC versus AC–D) and median overall survival (OS) was 22.6, 25.7, and 25.0 months (P = 0.09 for AC versus D, P = 0.13 for AC versus AC–D) in the AC, D, and AC–D, respectively. Conclusion: There was no difference in the TTF among the three arms. However, there was a trend toward a better response and better OS in the D than in the AC.

MGMT and MLH1 promoter methylation versus APC, KRAS and BRAF gene mutations in colorectal cancer: indications for distinct pathways and sequence of events

Background: To study how caretaker gene silencing relates to gatekeeper mutations in colorectal cancer (CRC), we investigated whether O6-methylguanine DNA methyltransferase (MGMT) and Human Mut-L Homologue 1 (MLH1) promoter hypermethylation are associated with APC, KRAS and BRAF mutations among 734 CRC patients. Methods: We compared MGMT hypermethylation with G:C > A:T mutations in APC and KRAS and with the occurrence of such mutations in CpG or non-CpG dinucleotides in APC. We also compared MLH1 hypermethylation with truncating APC mutations and activating KRAS and BRAF mutations. Results: Only 10% of the tumors showed both MGMT and MLH1 hypermethylation. MGMT hypermethylation occurred more frequently in tumors with G:C > A:T KRAS mutations (55%) compared with those without these mutations (38%, P < 0.001). No such difference was observed for G:C > A:T mutations in APC, regardless of whether mutations occurred in CpG or non-CpG dinucleotides. MLH1 hypermethylation was less common in tumors with APC mutations (P = 0.006) or KRAS mutations (P = 0.001), but was positively associated with BRAF mutations (P < 0.001). Conclusions: MGMT hypermethylation is associated with G:C > A:T mutations in KRAS, but not in APC, suggesting that MGMT hypermethylation may succeed APC mutations but precedes KRAS mutations in colorectal carcinogenesis. MLH1-hypermethylated tumors harbor fewer APC and KRAS mutations and more BRAF mutations, suggesting that they develop distinctly from an MGMT methylator pathway.

Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer

Background: We demonstrated that circulating tumor cell (CTC) number at baseline and follow-up is an independent prognostic factor in metastatic colorectal cancer (mCRC). This analysis was undertaken to explore whether patient and treatment characteristics impact the prognostic value of CTCs. Patients and methods: CTCs were enumerated with immunomagnetic separation from the blood of 430 patients with mCRC at baseline and on therapy. Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of ≥3 or <3 CTCs/7.5 ml, respectively. Subgroups were analyzed by line of treatment, liver involvement, receipt of oxaliplatin, irinotecan, or bevacizumab, age, and Eastern Cooperative Oncology Group performance status (ECOG PS). Results: Seventy-one percent of deaths have occurred. Median follow-up for living patients is 25.8 months. For all patients, progression-free survival (PFS) and overall survival (OS) for unfavorable compared with favorable baseline CTCs is shorter (4.4 versus 7.8 m, P = 0.004 for PFS; 9.4 versus 20.6 m, P < 0.0001 for OS). In all patient subgroups, unfavorable baseline CTC was associated with inferior OS (P < 0.001). In patients receiving first- or second-line therapy (P = 0.003), irinotecan (P = 0.0001), having liver involvement (P = 0.002), ≥65 years (P = 0.0007), and ECOG PS of zero (P = 0.04), unfavorable baseline CTC was associated with inferior PFS. Conclusion: Baseline CTC count is an important prognostic factor within specific subgroups defined by treatment or patient characteristics.

PLA2 (group IIA phospholipase A2) as a prognostic determinant in stage II colorectal carcinoma

Background: Approximately 30% of all colorectal cancer (CRC) patients are diagnosed with stage II disease. Adjuvant therapy is not widely recommended. However, it is well established that a subgroup of patients with stage II are at high risk for recurrence within their lifetime and should be considered for adjuvant chemotherapy. The present work was designed to assess the value of group IIA phospholipase A2 (PLA2) as a predictor of disease outcome in stage II CRC patients with long-term follow-up. Patients and methods: The present study comprises a series of 116 patients who underwent bowel resection for stage II CRC during 1981–1990 at Turku University Hospital. Archival paraffin-embedded CRC tissue samples were used to prepare tissue microarray blocks for immunohistochemical staining with PLA2. Results: Fifty-five percent of all tumors were positive for PLA2. There was no significant correlation between PLA2 expression and age, sex, depth of invasion and lymph node status. In Kaplan–Meier survival analysis, there was a significant (P = 0.010) difference in disease-free survival (DFS) between patients with negative tumors (longer DFS) and those with positive tumors. The same was true with disease-specific survival (DSS), patients with PLA2-negative tumors living significantly longer (P = 0.025). In multivariate (Cox) survival analysis, however, PLA2 was not an independent predictor of DFS or DSS. In subgroup analysis, the right-sided tumors with negative PLA2 staining had remarkably better prognosis (P = 0.010) than PLA2-positive left-sided tumors. Conclusions: Quantification of PLA2 expression seems to provide valuable prognostic information in stage II CRC, particularly in selecting the patients at high risk for recurrent disease who might benefit from adjuvant therapy.

Phase I trial of adjuvant hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone plus systemic oxaliplatin, 5-fluorouracil and leucovorin in patients with resected liver metastases from colorectal cancer

Background: The purpose of the study was to determine the maximum tolerated dose of systemic oxaliplatin (oxal), 5-fluorouracil (5-FU) and leucovorin (LV) that could be administered with hepatic arterial infusion (HAI) of floxuridine (FUDR) and dexamethasone (Dex) in the adjuvant setting after hepatic resection. Methods: Thirty-five patients with resected liver metastases were entered into a phase I trial using HAI FUDR/Dex with escalating doses of oxal and 5-FU. Results: The initial dose of HAI FUDR was fixed at 0.12 mg/kg x pump volume divided by pump flow rate plus Dex infused over the first 2 weeks of a 5-week cycle. Systemic chemotherapy was delivered on days 15 and 29 with the doses of oxal escalated from 85 to 100 mg/m2 and the 5-FU 48-h continuous infusion doses from 1000 to 2000 mg/m2. The LV dose was fixed at 400 mg/m2. Dose-limiting toxic effects were diarrhea, 8.5%, and elevated bilirubin, 8.5%. With a median follow-up of 43 months, the 4-year survival and progression-free survival were 88% and 50%, respectively. Conclusions: Adjuvant therapy after liver resection with HAI FUDR/Dex plus systemic oxal at 85 mg/m2 and 5-FU by continuous infusion at 2000 g/m2 with LV at 400 mg/m2 is feasible and appears effective. Randomized studies comparing this regimen to systemic FOLFOX are suggested.

Phase II trial of docetaxel-irinotecan combination in advanced esophageal cancer

Background: Preclinical evidence suggests synergy between docetaxel and irinotecan, two drugs active in esophagogastric cancer. We previously demonstrated the safety of docetaxel 35 mg/m2 and irinotecan 50 mg/m2 given on days 1 and 8 of a 21-day schedule. Materials and methods: Patients who had unresectable/metastatic squamous cell carcinoma or adenocarcinoma of the esophagus, measurable disease, Eastern Cooperative Oncology Group performance status of zero to two, and normal bilirubin were eligible. Tumor assessment was carried out every three cycles. Results: We enrolled 29 chemotherapy-naive (CN) and 15 chemotherapy-exposed (CE) eligible patients. Principal toxic effects were diarrhea, neutropenia, and hyperglycemia. There were no toxic deaths. There was one early death, from myocardial infarction. Among 26 CN and assessable patients, there were seven (26.9%) with a partial response (PR) and one (3.8%) with a complete response (CR). There were two PRs and one CR among the patients with CE disease. Median time to progression for CN patients was 4.0 months and for CE patients 3.5 months. Median survival for CN eligible patients was 9.0 months and for CE patients 11.4 months. Conclusions: Docetaxel–irinotecan combination given on a weekly x 2 of 3 schedule is promising in the treatment of advanced esophageal cancer.

Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and i.v. vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer

Background: The study compared the efficacy of a first-line treatment with day 1 i.v. vinorelbine (NVBiv) and day 8 oral vinorelbine (NVBo) versus docetaxel (DCT) in a cisplatin-based combination in advanced non-small-cell lung cancer, in terms of time to treatment failure (TTF), overall response, progression-free survival (PFS), overall survival (OS), tolerance and quality of life (QoL). Methods: Patients were randomly assigned to receive cisplatin 80 mg/m2 with NVBiv 30 mg/m2 on day 1 and NVBo 80 mg/m2 on day 8 every 3 weeks, after a first cycle of NVBiv 25 mg/m2 on day 1 and NVBo 60 mg/m2 on day 8 (arm A) or cisplatin 75 mg/m2 and DCT 75 mg/m2 on day 1 every 3 weeks (arm B), for a maximum of six cycles in both arms. Results: From 2 February 2004 to 1 January 2006, 390 patients were entered in a randomised study and 381 were treated. The patient characteristics are as follows (arms A/B): metastatic (%) 80.5/84.8; patients with three or more organs involved (%) 45.3/40.8; median age 59.4/62.1 years; male 139/146; squamous (%) 34.2/33.5; adenocarcinoma (%) 41.6/39.3; median TTF (arms A/B in months) [95% confidence interval (CI)]: 3.2 (3.0–4.2), 4.1 (3.4–4.5) (P = 0.19); overall response (arms A/B) (95% CI): 27.4% (21.2% to 34.2%), 27.2% (21.0% to 34.2%); median PFS (arms A/B in months) (95% CI): 4.9 (4.4–5.9), 5.1 (4.3–6.1) (P = 0.99) and median OS (arms A/B in months) (95% CI): 9.9 (8.4–11.6), 9.8 (8.8–11.5) (P = 0.58). The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B, respectively. Main haematological toxicity was grade 3–4 neutropenia: 24.4% (arm A) and 28.8% (arm B). QoL as measured by the Lung Cancer Symptom Scale was similar in both arms. Conclusions: Both arms provided similar efficacy in terms of response, time-related parameters and QoL, with an acceptable tolerance profile. In the current Global Lung Oncology Branch trial 3, NVBo was shown to be effective as a substitute for the i.v. formulation. This can relieve the burden of the i.v. injection on day 8 and can optimise the hospital's resources and improve patient convenience.

The NER proteins are differentially expressed in ever smokers and in never smokers with lung adenocarcinoma

Background: The expression levels of excision repair cross-complementation group 1 (ERCC1), replication protein A (RPA) and xeroderma pigmentosum group F (XPF) nucleotide excision repair proteins may be important in the response to platin-based therapy in lung cancer patients. It is not known whether ERCC1, RPA and XPF expression levels differ between ever smokers (ES) and never smokers (NS). Patients and methods: ERCC1, RPA and XPF expression levels were immunohistochemically evaluated in 125 patients with resected lung adenocarcinoma (AC) and carefully reviewed smoking status. Results: ERCC1 was correlated with XPF (P = 0.001), but not with RPA (P = 0.11). In the univariate analysis, ERCC1 and XPF levels were higher in NS compared with ES (P = 0.004 and P = 0.003, respectively). In the multivariate analysis, the smoking status was predictive of the ERCC1 level [odds ratio (OR) 2.5, 95% confidence interval (CI) 1.03–6.2] after adjustment for variables linked to the smoking status, including age and the presence of bronchioloalveolar (BAC) features. The smoking status was also predictive of both RPA (OR 6.7, 95% CI 1.5–33.3) and XPF levels (OR 12.5, 95% CI 2.9–50) after adjusting for age, sex and BAC features. Conclusion: In patients with resected lung AC, ERCC1, RPA and XPF expression levels are higher in NS compared with ES.

Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer

Background: This randomized, phase II study assessed the activity of oblimersen sodium, a Bcl-2 antisense oligonucleotide, administered before docetaxel (Taxotere) to patients with castration-resistant prostate cancer. Patients and methods: Chemotherapy-naive patients with prostate-specific antigen (PSA) progression and testosterone ≤0.5 ng/ml received docetaxel 75 mg/m2 on day 1 or oblimersen 7 mg/kg/day continuous i.v. infusion on days 1–7 with docetaxel 75 mg/m2 on day 5 every 3 weeks for ≤12 cycles. Primary end points were confirmed PSA response (Bubley criteria) and major toxic events. Results: Confirmed PSA response was observed in 46% and 37% of 57 and 54 patients treated with docetaxel and docetaxel–oblimersen, respectively. Partial response (RECIST) was achieved in 18% and 24%, respectively. Oblimersen added to docetaxel was associated with an increase in the incidence of grade ≥3 fatigue, mucositis, and thrombocytopenia. Major toxic events were reported in 22.8% and 40.7% of patients with docetaxel and docetaxel–oblimersen, respectively. Conclusions: The primary end points of the study were not met: a rate of confirmed PSA response >30% and a major toxic event rate <45% were not observed with docetaxel–oblimersen.

FDG-PET for assessment of early treatment response after four cycles of chemotherapy in patients with advanced-stage Hodgkin's lymphoma has a high negative predictive value

Background: As positron emission tomography (PET) seems to be a powerful prognostic marker in the treatment of Hodgkin's lymphoma (HL), we analysed the prognostic value of PET after four cycles of combination therapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) in patients with advanced-stage HL. Patients and methods: From January 2004 to March 2007, 50 patients with newly diagnosed HL in clinical stages IIB with large mediastinal mass or extranodal disease, III and IV were treated according to the HD15 protocol of the German Hodgkin Study Group. All patients received a PET scan after four cycles of BEACOPP (PET-4). Results: Of the overall group, 14 of 50 patients had a positive PET-4 while 36 had a negative PET-4. At a median observation time of 25 months, 2 of the 14 patients with a positive PET-4 had progressed or relapsed, while there was no progression or relapse in PET-4-negative patients. Conclusion: Our results indicate a very good negative predictive value of PET-4 in advanced-stage HL patients treated with BEACOPP.

Phase II study of 3-AP Triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma

Background: Treatment options for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are limited with response rates to cytotoxic chemotherapy of ~30% and median survival of 6 months. Patients and methods: In a multicentre phase II study, 32 patients with recurrent or metastatic HNSCC received 3-AP Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), an inhibitor of ribonucleotide reductase, 96 mg/m2, daily for 4 days every 14 days (one cycle). Eligibility criteria required Eastern Cooperative Oncology Group performance status (ECOG PS) of zero to two with a life expectancy of >3 months; one prior chemotherapy regimen was allowed. Results: Thirty patients were assessable for response and toxicity. Median age was 57 years (range 36–79) and median ECOG PS was one (range 0–2). Thirteen patients had previously been treated with chemotherapy. A total of 130 cycles were administered with a median number of cycles of 3.5 (range 1–8). Mild anaemia (40%), nausea (22%) and fatigue (22%) were commonly reported with G3 and G4 neutropenia documented in 22% and 22%, respectively. Overall response rate was 5.9% (95% confidence interval 0.2% to 28.7%). One patient achieved a partial response, eight had stable disease and 21 progressive disease. Median time to disease progression was 3.9 months. Conclusions: 3-AP Triapine as a single agent, at this dose and schedule, is well tolerated but has only minor activity in the treatment of advanced HNSCC.

Travel warning with capecitabine

Tamoxifen contraindicated in women with hereditary angioedema?

Immune thrombocytopenic purpura (ITP) and breast cancer. Does adjuvant therapy for breast cancer improve platelet counts in ITP?

Successful treatment of ifosfamide-induced hyponatremia with AVP receptor antagonist without interruption of hydration for prevention of hemorrhagic cystitis

BRCA2 splice site mutations in an Italian breast/ovarian cancer family

Reply to BRCA2 splice site mutations in an Italian breast/ovarian cancer family