Judith S. Kaur

Annual report to the nation on the status of cancer, 1975–2004, featuring cancer in American Indians and Alaska Natives

The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate annually to provide updated information on cancer occurrence and trends in the U.S. The 2007 report features a comprehensive compilation of cancer information for American Indians and Alaska Natives (AI/AN).

Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years

BACKGROUND Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor-positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence. METHODS We conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years. Our primary end point was disease-free survival. RESULTS We enrolled 1918 women. After a median follow-up of 6.3 years, there were 165 events involving disease recurrence or the occurrence of contralateral breast cancer (67 with letrozole and 98 with placebo) and 200 deaths (100 in each group). The 5-year disease-free survival rate was 95% (95% confidence interval [CI], 93 to 96) with letrozole and 91% (95% CI; 89 to 93) with placebo (hazard ratio for disease recurrence or the occurrence of contralateral breast cancer, 0.66; P=0.01 by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, the interval from the last dose of aromatase-inhibitor therapy, and the duration of treatment with tamoxifen). The rate of 5-year overall survival was 93% (95% CI, 92 to 95) with letrozole and 94% (95% CI, 92 to 95) with placebo (hazard ratio, 0.97; P=0.83). The annual incidence rate of contralateral breast cancer in the letrozole group was 0.21% (95% CI, 0.10 to 0.32), and the rate in the placebo group was 0.49% (95% CI, 0.32 to 0.67) (hazard ratio, 0.42; P=0.007). Bone-related toxic effects occurred more frequently among patients receiving letrozole than among those receiving placebo, including a higher incidence of bone pain, bone fractures, and new-onset osteoporosis. No significant differences between letrozole and placebo were observed in scores on most subscales measuring quality of life. CONCLUSIONS The extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease-free survival and a lower incidence of contralateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov numbers, NCT00003140 and NCT00754845.).

Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer.

PURPOSE Vaginal dryness and dyspareunia are significant estrogen-depletion symptoms that affect many breast cancer survivors. The present trial was developed to evaluate the nonhormonal vaginal lubricating preparation, Replens, for alleviating these symptoms. MATERIALS AND METHODS A double-blind, crossover, randomized clinical trial was developed. Patients received 4 weeks of Replens (Columbia Research Laboratories, Rockville Centre, NY) followed by a 1-week washout period followed by 4 weeks of a placebo lubricating product, or vice versa. Weekly patient-completed diaries were used for measuring efficacies and toxicities of therapy. RESULTS The 45 assessable patients provided well-balanced treatment groups. During the first 4 weeks, average vaginal dryness decreased by 62% and 64% in the placebo and Replens groups, respectively (P = .3). Average dyspareunia scores also improved by 41% and 60%, respectively (P = .05). Crossover analysis indicated that the bulk of the beneficial effects appeared within the first 2 weeks of the first treatment and remained constant thereafter. Both treatments were relatively well tolerated. CONCLUSION Both Replens and the placebo appear to substantially ameliorate vaginal dryness and dyspareunia in breast cancer survivors.

Cancer among American Indians and Alaska Natives in the United States, 1999–2004

Cancer incidence rates vary among American Indian and Alaska Native (AI/AN) populations and often differ from rates among non‐Hispanic whites (NHWs). However, the misclassification of race for AI/AN cancer cases in central cancer registries may have led to underestimates of the AI/AN cancer burden in previous reports.

Combination of paclitaxel and carboplatin as second-line therapy for patients with metastatic melanoma†‡

Patients with metastatic melanoma (MM) have very few therapy options. Based on reports of responses to paclitaxel and carboplatin (PC), 31 patients with MM were treated with PC.

A phase II study of ABT-510 (thrombospondin-1 analog) for the treatment of metastatic melanoma.

Objectives:Thrombospondins are natural inhibitors of angiogenesis, tumor metastases, and tumor growth (melanoma). ABT-510 is a synthetic analog of thrombospondin-1, well tolerated in phase I studies. We conducted a phase II trial evaluating the clinical efficacy of ABT-510 and its effects on biomarkers of angiogenesis and immunity in patients with metastatic melanoma (MM). Patients and Methods:A 2-stage phase II clinical trial was conducted to assess the clinical efficacy, safety, and pharmacodynamic effects (angiogenesis and immunity) of ABT-510 in patients with stage IV melanoma. The primary endpoint was 18-week treatment failure rate. Patients self-administered 100 mg of ABT-510 subcutaneously twice daily. Blood samples were collected at baseline and every 3 weeks while on therapy. Eligible patients demonstrated measurable disease, good performance status and no evidence of intracranial metastases. Correlative laboratory studies evaluated biomarkers of angiogenesis and immunity. Results:Twenty-one patients were enrolled. Most patients were stage M1c (71%) and all had prior therapy for MM. Only 3 of the first 20 patients enrolled were progression free and on treatment at 18 weeks resulting in early termination of the study. Decreases in peripheral blood VEGF-A levels and VEGF-C levels, and CD146 and CD34/133 counts relative to pretreatment were detected. Limited changes in antitumor T cell immunity were observed. Conclusions:ABT-510 therapy administered at 100 mg twice/day in patients with MM did not demonstrate definite clinical efficacy. Further dose escalation or combination with cytotoxic therapy may be more effective therapeutically.

Disparities in Cancer Mortality and Incidence Among American Indians and Alaska Natives in the United States

OBJECTIVES We used improved data on American Indian and Alaska Native (AI/AN) ancestry to provide an updated and comprehensive description of cancer mortality and incidence among AI/AN populations from 1990 to 2009. METHODS We linked the National Death Index and central cancer registry records independently to the Indian Health Service (IHS) patient registration database to improve identification of AI/AN persons in cancer mortality and incidence data, respectively. Analyses were restricted to non-Hispanic persons residing in Contract Health Service Delivery Area counties in 6 geographic regions of the United States. We compared age-adjusted mortality and incidence rates for AI/AN populations with White populations using rate ratios and mortality-to-incidence ratios. Trends were described using joinpoint analysis. RESULTS Cancer mortality and incidence rates for AI/AN persons compared with Whites varied by region and type of cancer. Trends in death rates showed that greater progress in cancer control was achieved for White populations compared with AI/AN populations over the last 2 decades. CONCLUSIONS Spatial variations in mortality and incidence by type of cancer demonstrated both persistent and emerging challenges for cancer control in AI/AN populations.

The impact of multi-modal therapy on survival for uterine carcinosarcomas

OBJECTIVES To investigate treatment outcomes of patients with carcinosarcoma of the uterus and to identify parameters predictive of survival. Secondary objectives included (a) the assessment of treatment failures as a function of histologic subtypes and (b) the impact of the new FIGO staging classification system. METHODS This is a retrospective outcomes analysis of 121 patients diagnosed with primary carcinosarcoma of the uterus. Clinical, surgical and pathological data were reviewed and patients were classified according to the new 2009 FIGO staging system for endometrial carcinoma. Survivorship curves were evaluated with the log-rank test and associations between events and variables with Cox proportional hazards model. RESULTS In the multivariate analyses for disease-specific survival (DSS) and disease-free survival (DFS), the only independent factors were FIGO stage, adjuvant chemotherapy after surgery and the presence of clear cell histology in the tumor. The 5-year DSS for stages I-II, III and IV was 59%, 22% and 9%, respectively. The administration of platin-based chemotherapy provided a significant benefit with regard to both DFS (OR=0.28; p=0.001) and DSS (OR=0.35; p=0.01). While radiotherapy (RT) appeared to control vaginal failures in all stages, pelvic RT did not impact DSS. Of importance, the epithelial component was the predominant histology in both the primary extrauterine metastases (94%) and the distant failure sites (82%). CONCLUSIONS This highly aggressive uterine malignancy warrants comprehensive surgical staging to assess tumor dissemination followed by systemic therapy in patients with both early and advanced stage disease.

A randomized phase 2 study of temozolomide and bevacizumab or nab-paclitaxel, carboplatin, and bevacizumab in patients with unresectable stage IV melanoma : a North Central Cancer Treatment Group study, N0775.

Increasing evidence shows chemotherapy in combination with vascular endothelial growth factor (VEGF) inhibition is a clinically active therapy for patients with metastatic melanoma (MM).

Breast cancer incidence among American Indian and Alaska Native women: US, 1999-2004

Breast cancer is a leading cause of cancer morbidity and mortality among American Indian and Alaska Native (AI/AN) women. Although published studies have suggested that breast cancer rates among AI/AN women are lower than those among other racial and ethnic populations, accurate determinations of the breast cancer burden have been hampered by misclassification of AI/AN race.