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Clinical Abstracts from Overseas: June 2007

OBTN, June 2007, Volume 1, Issue 5

Articles in this issue include: 1) Norway: Hopes for Trastuzamab Use in Endometrial Cancer 2) Switzerland: New Guidelines Highlight Use of Bisphosphonates in Elderly Patients With Bone Metastases 3) Italy: Bringing Out All of the Artillery to Fight Mesothelioma 4) Poland: Radiotherapy in Lung Cancer: Former Soviet Bloc Countries at a Disadvantage 5) United Kingdom: --Are More Transfusions Being Used in Patients With Cancer? --Watchful Waiting Advanced Even for Advanced Prostate Cancer --Exemestane Proven Useful for Breast Cancer After Switching From Tamoxifen

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â–º NORWAY Hopes for Trastuzamab Use in Endometrial Cancer

The link between HER-2/neu receptors and endometrial cancer is growing stronger, and this may point the way to treatment with existing therapies, according to research conducted in Norway.

Samples from 316 patients with endometrial carcinoma were used to determine the presence of these receptors, found in many patients with breast cancer, and overall how epidermal growth factor receptor (EGFR) was expressed in this tissue. The researchers found that in 23% of the patients, the preoperative curettage material had evidence of HER-2/neu expression. The study also revealed that 25% of patients had overexpression of EGFR, but this was not correlated with any prognostic measures. They did find that those tumors with HER-2/neu overexpression were related to aggressive growth and proliferation.

Presenting their findings at the 2007 American Association of Cancer Researchers annual meeting in Los Angeles, the Norwegian researchers stated that these samples also demonstrated lower levels of estrogen and progesterone receptors compared with tissue that did not show HER-2/neu overex¬pression.

Since trastuzamab is used as a first-line therapy in patients with breast cancer associated with HER-2/neu receptors, it is hoped that trastuzamab can also be useful in patients with endometrial tumors expressing this receptor. A large trial is being undertaken in the United States to test its efficacy for endometrial carcinoma.

Engelson IB, Stefansson IM, Beroukhim R, et al: HER-2/neu expression is associated with increased tumor cell proliferation, loss of hormone receptors, and an aggressive phenotype in a population-based setting of endometrial carcinomas. Presented at the 2007 annual meeting of the American Association of Cancer Researchers, Los Angeles, April 18, 2007.

â–º SWITZERLAND New Guidelines Highlight Use of Bisphosphonates in Elderly Patients With Bone Metastases

Used in the United States for many years in younger patients with bone cancer, bisphosphonate agents have been especially valuable in treating hypercalcemia. However, little data exist regarding their use in elderly patients, and physicians have often been warned to be careful in their choice of bisphosphonate because of problems in those with impaired renal function. The International Society of Geriatric Oncology, based in Genolier, Switzerland, had recently completed a literature review on this population and issued its recommendations.

The Society’s task force, headed by Belgian physicians, specified that not only are intravenously administered bisphosphonates preferred for the treatment of hypercalcemia, but these agents (all forms) are desirable for the prevention of brittle bones in patients with bone metastases.

The guidelineauthors also specified that ibandronate, pamidronate, and zoledronic acid are effective at relieving acute pain in patients with bone metastases.

Creatinine clearance should be monitored because of possible renal impairment, and a drug that is less toxic to the kidneys (e.g., ibondronate) may be preferable in certain patients. Another possible side effect of bisphosphonate therapy is osteonecrosis of the jaw; the guidelines suggest that oral and dental examination be conducted before initiating therapy.

The task force noted that although the literature does address the elderly population with osteoporosis taking these products, more research is needed to further define the role of bisphosphonates in geriatric populations with bone metastases.

Body JJ, Coleman R, Clezardin P, et al: International Society of Geriatric Oncology (SIOG) clinical practice recommendations for the use of bisphosphonates in elderly patients

2007 Mar;43(5):852-8. Epub 2007 Jan 26

. Eur J Cancer .

â–º ITALY Bringing Out All of the Artillery to Fight Mesothelioma

The treatment of pleural mesothelioma has hinged on catching the disease early, attempting surgical resection, and hoping (with little success) that metastases did not occur. In advanced-stage disease, management strategy in general consisted of palliative care only. Italian researchers have tried a new approach to the disorder— a complex, staged approach using four modalities—have reported some success in a nonrandomized, noncontrolled study.

In this phase II trial, 49 patients (41 men; median age, 61 yr) with stage II to III disease were studied over a six-year period. First, they were given interleukin-2 (18 X 106 IU/ day for three days) administered through the pleura. The patients then underwent pleurectomy and decortication. Postoperatively, they were given epidoxorubicin (25 mg/m2 for three days) administered intrapleurally, with another cycle of interleukin-2 therapy, adjuvant radiotherapy (30 Gy), up to six cycles of systemic chemotherapy with cisplatin and gemcitabine. Finally, their long-term therapy comprised interleukin-2 (3 X 106 IU/day) given subcutaneously.

Median patient survival is 26 months, with patients with stage II disease living for a median 31 months. Survival at two years was 60%, but survival at five years was 23%. The researchers reported that only four patients experienced significant postoperative morbidity. Although this trial was not scientifically rigorous, the authors believe that this therapeutic regimen shows some promise for a carcinoma in which even promise offers hope.

2007 Mar;2(3):237-42.

Lucchi M, Chella A, Melfi F, et al: Four-modality therapy in malignant pleural mesothelioma: A phase II study. J Thorac Oncol

â–º POLAND Radiotherapy in Lung Cancer: Former Soviet Block Countries at a Disadvantage

For many former Soviet Union members and Eastern European countries, health care indicators as well as health care access has lagged behind those of other Western nations. Researchers from the Curie Memorial Cancer Centre and Institute of Oncololgy in Warsaw, Poland, surveyed 28 countries to better understand the health care gap in terms of radiotherapy for lung cancer.

The researchers sent questionnaires to radiation oncologists in each country, classified as former Soviet states and other Eastern/Central European countries. Representatives from 24 states responded to the survey.

The results revealed a noticeable gap in access to modern treatment facilities (including 3D planning systems and in the number of available linear accelerators), patients receiving radiotherapy, use of radiotherapy for pallation, and use of radiotherapy as an adjunct to surgery.

According to the survey, 57% of patients with non—small-cell lung cancer received sequential chemotherapy and radiotherapy, 30% received only radiotherapy, and 10% received concomitant chemotherapy and radiotherapy. The treatment patterns from accepted clinical guidelines varied the most in former Soviet states. The authors pointed out that equipment was particularly lacking in these areas compared with other Central and Eastern European countries.

Kepka L, Danilova V, Saghatelyan T, et al: Resources and management strategies for the use of radiotherapy in the treatment of lung cancer in Central and Eastern European countries: Results of an International Atomic Energy Agency survey

2007 May;56(2):235-245, Epub 2007 Jan 30.

. Lung Cancer

â–º UNITED KINGDOM Are More Transfusions Being Used in Patients With Cancer?

The controversy over whether erythropoietin is appropriate for patients with cancer continues to heat up. Although recent evidence showed that the use of these products can be associated with higher death rates, researchers from the Norfolk and Norwich University Hospital National Health Service Trust, Norwich, United Kingdom, believe that erythropoietin might have a place in light of rising transfusion rates in oncological practice.

The researchers retrospectively reviewed a total of 1,611 transfusions given in a hospital setting to a total of 881 patients, from an overall total of 25,264 treatment sessions in 6,137 patients over a three-year period.

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The analysis demonstrated that the transfusion rate in patients with cancer jumped 25% over the course of the study, ending in August 2004. They pointed out that the transfusion rate rose at the same time the trigger point for transfusions increased as well. At the beginning of the study, the mean hemoglobin level at the time of transfusion was 8.53 g/dL, but by study’s end, the mean hemoglobin level at the transfusion was 8.86 g/ dL ( < .001). This was accompanied by increased numbers of treatment sessions and of patients who were receiving chemotherapy alone or in combination with radiotherapy.

The researchers found that patients with cancer of the lung, ovaries, or pancreas were more likely to receive transfusions, compared with other oncologic sites.

They speculate that in order to alleviate the need for transfusions, especially in patients at high risk for anemia, other alternatives, such as erythropoietin, should be considered.

Dernedde U, Dernedde R, Shepstone L, et al: Three-year single institution audit on transfusion requirements in oncology patients

2007 May;19(4):223-7. Epub 2006 Dec 11.

. Clin Oncol (R Coll Radiol)

â–º UNITED KINGDOM

Watchful Waiting Advanced Even for Advanced Prostate Cancer

A prospective observational trial of 430 patients conducted in England demonstrated that in those even with locally advanced or metastatic prostate cancer, only slightly more than half of the deaths over a five-year period were attributable to carcinoma.

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Over the mean five-year follow-up of these patients, all of whom required hormone therapy (mean age, 73 yr; age range, 53—93 yr), 48 of the 109 total deaths (mortality, 25% overall) were from causes other than cancer. However, the researchers pointed out that the prostate-specific antigen level in patients who died of cancer (mean, 118 ng/mL) was significantly higher than patients whose deaths were related to other causes (mean, 23 ng/mL) ( < .001). Only 9% of those with prostate-specific antigen levels of below 50 ng/mL died from cancer-related causes over the five-year follow-up.

At the European Association of Urology annual meeting in Berlin, the researchers pointed out that cancer-related deaths decreased as a percentage of population with advancing age (Figure). As a result, they believe that, particularly in older patients with advanced prostate cancer, watchful waiting may be further justified, particularly if prostate-specific antigen levels are relatively low.

Wadwa V, Weston R, Parr N: A large proportion of patients with advanced prostate cancer continue to die of non-cancer causes after five years of follow-up. Presented at the annual meeting of the European Association of Urology, Berlin, March 21, 2007.

â–º UNITED KINGDOM

Exemestane Proven Useful for Breast Cancer After Switching From Tamoxifen

Aromatase inhibitors, such as letrazole, have been found to be more effective than tamoxifen in improving survival in patients with breast cancer. These agents have also safety profiles that were similar to that for tamoxifen. They are now also being found to offer benefits when used as continuing therapy, after patients had received at least years of tamoxifen therapy.

A study group from the United Kingdom tested the use of another aromatase inhibitor, exemestane. All of the 4,700 postmenopausal patients had received tamoxifen for two to three years before being randomized to continue therapy or receive exemestane until a total of five years of endocrine therapy was achieved.

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The study group found a clinical advantage associated with this nonsteroidal aromatase inhibitor over tamoxifen (survival hazard ratio, 0.75; < .0001). Two hundred twenty-two deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group.

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As with the other nonsteroidal aromatase inhibitors, exemestane was also associated with lower bone mineral density by six months of therapy (2.7% decrease at the lumbar spine) but this moderated to a 1.0% decrease by year 2 of exemestane therapy < .0001) compared with patients continuing on tamoxifen therapy. The risk of fractures was increased in the exemestane group but none of the patients had treatment-related osteoporosis during the follow-up period.

Coombes RC, Kilburn LS, Snowden CF, et al: Survival and Safety of exemestane versus tamoxifen after 2-3 years’ tamoxifen treatment (Intergroup Exemestane Study): A randomized controlled trial

2007 Feb 17;369(9561):559-70.

Coleman RE, Banks LM, Girgis SI, et al: Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): A randomised controlled study

2007 Feb;8(2):119-27.

. Lancet . Lancet Oncol