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Clinical Abstracts from Overseas

OBTN, March 2008, Volume 2, Issue 3

Articles in this issue include:United Kingdom: The Pill's Anti-Ovarian Cancer Effect Lasts for Decades The Netherlands.

UNITED KINGDOM

The Pill’s Anti-Ovarian Cancer Effect Lasts for Decades

Do oral contraceptives’ prophylactic benefits outweigh their risks? The controversy continues to rage on, with new evidence revealing that women who stop taking the pill after long-term use continue to experience some preventive effects against ovarian cancer, for perhaps much longer than anticipated.

Researchers from the United Kingdom conducted a meta-analysis of 45 studies from around the world, which comprised more than 23,000 women with ovarian cancer and 87,000 controls. Slightly more than one-third of all of the study participants had been taking oral contraceptives (of varying estrogen—progestin doses and potencies). The mean duration of oral contraceptive use was five years.

The researchers found that if women did not take oral contraception, 1.2% would be expected to develop ovarian cancer. Of those using the pill, the incidence dropped by a third, to 0.8%. They also found that for women who were using oral contraceptives for 15 years and then stopped, their risk of ovarian cancer seemed to be 15% less than those who never used the pill even 30 years later.

Based on these results, it is possible that use of oral contraception may have prevented approximately 200,000 ovarian carcinomas and perhaps 100,000 deaths globally.

Collaborative Group on Epidemiological Studies of Ovarian Cancer: Ovarian cancer and oral contraceptives: Collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls

2008;371:303-314.

. The Lancet

THE NETHERLANDS

Catheter-Related Infection Prevention Improves With Specialized Rinse

Patients with hematologic malignancies who require central venous catheters tend to experience fibrin build-up at the point of insertion. This increases the risk of staphylococcus infection, particularly of the coagulase-negative variety. Physicians from Leiden University, the Netherlands studied whether the use of a urokinase-containing rinse, which breaks up the fibrin, would reduce the risk of infection associated with the in-dwelling catheter.

In this controlled double-blind study, patients were randomly assigned to receive the urokinase or saline rinse three times each week. The dose of urokinase used in the rinse was 5 mL in each 5,000 U/mL.

The investigators found that 42% of the patients given the placebo rinse had a positive staph culture, compared with 26% of those given the urokinase rinse (relative risk, 0.61). The actual infection rates were 14.1% and 1.2%, respectively, meaning that patients using the rinse had a 91% lower relative risk of coagulase-negative staph infection associated with the catheter use compared with those receiving placebo. This translated into a far lower rate of staphylococcal-associated effects, and also thrombosis associated with the catheter (likely because of the thrombolytic activity of the urokinase). They did not note any serious bleeding related to the use of the urokinase rinse.

These results indicate that while not perhaps fully preventing the presence of staphylococcus, this intervention greatly reduces the likelihood of infection and its associated complications in patients with hematologic cancer.

Relative risk of staphylococcal presence in culture and infection

Presence of Staph in Culture

Staph Infection

Relative Risk With Urokinase

Urokinase rinse group

26%

1.2%

61%

Placebo group

42%

  1. 14.1%

9%

Van Rooden C, Schippers ER, Guiot HFL, et al: Prevention of coagulase-negative staphylococcal central venous catheter—related infection using urokinase rinses: A randomized, double-blind controlled trial in patients with hematologic malignancies.

2008;26:428-433.

J Clin Oncol

ITALY

Obesity May Help Survival in Women Who Have Endometrial Cancer

Does obesity interfere with the ability of the surgeon to perform lymphadenectomy for cancer staging purposes, and what is the overall effect of obesity on treatment and survival in women with endometrial cancer? Led by a team from the University of Turin, Italy, a collaborative group of oncologists conducted a retrospective study of the medical records of 766 women to help answer these questions.

Women with a body mass index of at least 30 kg/m2 were classified as obese. All others were labeled nonobese. The progress of the women was followed for a median 38 months.

The study revealed that any difference between the frequencies of staging lymphadectomy in obese and nonobese women was not significant. The research group did find that women with body mass indices below 30 kg/ m2 more often underwent pelvic irradiation compared with obese women. Of most interest, the four-year survival in women classified as obese with endometrial cancer was higher than for nonobese women (40% relative difference based on all-cause death; 10% vs. 6%, respectively).

Martra F, Kunos C, Gibbons H, et al: Adjuvant treatment and survival in obese women with endometrial cancer: An international collaborative study.

2008;198:89. e1—8.

Am J Obstet Gynecol

GERMANY

One-Two Punch for B-cell Lymphoma in the Elderly

Eight cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP-14) is the usual treatment of diffuse CD20-positive B-cell lymphoma in older patients. New study results from Saarland University Medical School, Hamburg, Germany, indicate that two cycles of the cytotoxic treatments can be eliminated if replaced with rituximab, with improved outcomes.

Overall three-year survival in elderly patients with diffuse B-cell lymphoma.

Therapy

3-yr Overall Survival

6 cycles CHOP-14

68%

8 cycles CHOP-14

66%

6 cycles CHOP-14

8 cycles rituximab

78%

8 cycles CHOP-14

8 cycles rituximab

72%

One thousand two hundred patients (age range, 60—80 yr) were randomized to receive either six or eight cycles of CHOP-14 alone (control group), or either six cycles of CHOP-14 plus eight doses of rituximab (R-CHOP-14) or eight cycles of CHOP-14 plus eight cycles of rituximab.

The primary endpoint, three-year event-free survival, was improved with the addition of rituximab. The researchers found that threeyear event-free survival was 47.2% after six cycles of CHOP-14 alone, 53.0% after eight cycles of CHOP-14 alone, 66.5% following six cycles of R-CHOP-14, and 63.1% after eight cycles of RCHOP- 14. Overall survival after three years is shown in the above Figure.

The authors conclude that based on the results of the four CHOP treatment regimens tested, six cycles of R-CHOP-14 should be preferred for elderly patients.

Pfreundschuh M, Schubert J, Ziepert M, et al: Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20 B-cell lymphomas: A randomised controlled trial (RICOVER-60)

2008; 9:206-116.

. Lancet Oncol

SOUTH KOREA

Predicting Survival by Counting Metastatic Lymph Nodes

In patients with stage III non—small cell lung cancer, the finding of metastatic lymph nodes remaining after neoadjuvant treatment has portended a poorer prognosis than patients in whom metastatic lymph nodes cannot be found. Oncologists from Yonsei University College of Medicine and Medical Center, Seoul, South Korea, attempted to assess exactly what the finding of residual diseased lymph nodes mean.

They studied 42 consecutive patients over a five years who had stage III non—small cell lung cancer who were treated with neoadjuvant chemotherapy (3 cycles of platinum-based chemotherapy with either gemcitabine [21 patients], paclitaxel [15 patients], or docetaxel [6 patients]). Of the study group, one experienced a complete pathological response. Twenty-four patients’ tumors regressed and were downstaged. Nine patients did not have evidence of lymph node metastases (21%), but 33 did (79%).

P

The disease-free survival rate after two years was 46% in those without lymph node metastases compared with 18% in patients in whom residual lymph node metastases remained. This difference was statistically significant ( = .03).

The oncologists assessed other factors that may affect survival in the group with lymph node metastases. They found that lower numbers of affected lymph nodes, younger age, and tumor response resulting in downstaging were significant predictors of disease-free survival. The patients with up to four residual lymph node metastases had a median disease-free survival of 14 months compared with those with at least five affected lymph nodes, who had a median survival of only five months. Multivariate analysis revealed that the number of affected lymph nodes was an independent predictor of disease-free survival in patients with stage III non—small cell lung cancer.

Kim SH, Cho BC, Choi HJ, et al: The number of residual metastatic lymph nodes following neoadjuvant chemotherapy predicts survival in patients with stage III NSCLC.

2007;Dec 21 [E-pub ahead of print].

Lung Cancer

POLAND

Do Chest X-Rays in Young Women Raise the Risk of Breast Cancer?

It is well known that exposure to excessive radiation is a risk factor for carcinogenesis. In women who have the BRCA1 gene, the possibility exists that chest x-rays may increase their risk of developing breast cancer later in life, according to Polish researchers.

Geneticists from the Pomeranian Medical University, Szczecin, Poland, tested their hypothesis in 158 women with breast cancer (without the BRCA1 gene) and 138 women who were found to carry the BRCA1 gene, contacted through a national breast cancer registry. They conducted medical histories on each woman to determine whether they had exposure to chest x-rays before age 30. The patients from the study and control groups were matched by age.

P

P

They found that women who had breast cancer and have the BRCA1 gene were more likely to report chest x-ray use (mean, 1.8 chest x-rays by age 30 vs. 1.0 for non-BRCA1 carriers, odds ratio = 1.8, = .002). This difference was also seen by age 20 (mean, 0.6 vs. 0.3, respectively; = .01).

The researchers conclude that early radiation exposure may in fact be a risk factor for breast cancer in BRCA1 carriers. They acknowledge that a prospective study to support these results is unlikely, but it is possible to conduct a much larger, retrospective study to confirm the findings.

Gronwald J, Pijpe A, Byrski T, et al: Early radiation exposures and BRCA1-associated breast cancer in young women from Poland.

2008;Jan18 (E-pub ahead of print).

Breast Cancer Res Treat

AUSTRALIA

Concurrent or Sequential Anthracycline and Docetaxel?

It is well documented that docetaxel is more effective than doxorubicin for women with advanced breast cancer. However, what about the combination of the two? Australian clinicians attempted to test whether the two drugs, when used in concurrent or sequential combination, positively influenced survival.

All of the women participating in the randomized trial had lymph node—positive metastases. A total of 2,887 women were given one of four treatments, with the first two being control group regimens: (1) doxorubicin 75 mg/m2 given in four cycles followed by three cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), (2) doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 given in four cycles in addition to three cycles of CMF, (3) three cycles of doxorubicin 75 mg/m2 succeeded by docetaxel 100 mg/m2 and then three CMF cycles, or (4) four cycles of doxorubicin 50 mg/m2 given concurrently with docetaxel 75 mg/m2 succeeded by three CMF cycles.

The mean five-year disease-free survival in patients taking either of the control regimens was 73%. Patients receiving sequential docetaxel therapy had slightly better survival (hazard ratio, 0.79), which was marginally better than in the concurrent docetaxel arm (hazard ratio, 0.83). Based on these results, the investigators believe that sequential docetaxel therapy added to an adjuvant doxorubicin and CMF regimen may result in better disease-free survival.

They noted that the overall relapse rates were somewhat lower than anticipated, and this may have skewed the results. The researchers believe additional trials may be necessary to confirm these findings.

Francis P, Crown J, Di Leo A, et al: Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial.

2008;100:121-133.

J Natl Cancer Inst