A Phase I Study of High-Dose Calcitriol in Combination with Temozolomide for Patients with Metastatic Melanoma

Background: Temozolomide is efficacious as an oral alternative for patients with metastatic melanoma (MM). Calcitriol has anti-proliferative properties and vitamin D receptor (VDR) polymorphisms are associated with alterations in melanoma susceptibility and progression. Methods: Tem 150 mg/m2 was administered on days 2–8 and 16–22 every 28 days. Calcitriol was given on days 1 and 15 every 28 days. VDR gene analysis was completed using PCR-RFLP based assays. Tolerability was the primary objective with secondary objectives of time to progression (TTP) and overall survival (OS). Results: Twenty pts with MM were registered. Cytopenias and thrombosis were the most common grade 3 or 4 toxicities. Median TTP was 1.8 mo. Pts with high-risk VDR genotype tt+/−ff (n = 6) had an OS of 3.8 mo from time of enrollment, compared to 7.4 mo for those with non-tt/ff genotypes (n = 11), although not statistically significant (HR = 1.20, 95% CI 0.41–3.53, p = 0.74). Conclusions: The extended dosing of Tem with calcitriol is a well-tolerated regimen. The trend toward improved OS in non-tt/ff VDR genotypes is consistent with prior studies associating the tt/ff genotype with biologic aggressiveness

Abstract 1922: Ethnic and racial differences in colorectal cancer

Abstract Introduction: The Women's Health Initiative (WHI) provides a robust database to determine whether differences in known colorectal cancer (CRC) risk factors influence ethnic and racial differences in incidence and mortality. Methods: The WHI is a multi-center longitudinal study of postmenopausal women age 50-79 years recruited from 40 centers across the US. Baseline self-administered questionnaires were used to collect self-identified ethnicity or race, other demographics and health status. Cancer screening information was collected annually and cancer diagnoses were centrally adjudicated. Cox proportional hazards regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for invasive CRC by ethnicity/race. Results: The ethnic and racial composition of the sample is 131,481 (84%) White, 14,323 (9%) African American (AA), 6,362 (4%) Hispanic, 694 (&amp;lt;1%) Native American and 4,148 (3%) Asian/Pacific Islander (API). After a mean follow-up of 10.8 years (SD 2.9), CRC incidence was highest among AA (annualized percent 0.14%), followed by Whites and Native Americans (0.12% each), API (0.10%) and Hispanics (0.08%). After adjustment for age and cohort assignment, Hispanics had a lower risk of CRC compared to Whites, HR 0.73 (95% CI: 0.54-0.97) (p=0.03), and AA had a marginally greater risk, HR 1.16 (95% CI: 0.99-1.34), p=0.06. Adjustment for other covariates, eliminated the difference in incidence between AA and Whites (HR 0.99, 95% CI: 0.82-1.20), however the difference in incidence between Hispanics and Whites increased (HR 0.68, 95% CI: 0.48-0.97), p = 0.03. Conclusions: Differences in CRC risk between Hispanics and Whites are not explained by sociodemographic or behavioral factors in the WHI cohort. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1922. doi:10.1158/1538-7445.AM2011-1922</jats:p

Racial Differences in Colorectal Cancer Incidence and Mortality in the Women's Health Initiative

BACKGROUND: Colorectal cancer (CRC) incidence and mortality rates are higher in African–Americans as compared with other racial/ethnic groups. The women’s health initiative (WHI) study sample was used to determine whether differences in CRC risk factors explain racial/ethnic differences in incidence and mortality. METHODS: The WHI is a longitudinal study of postmenopausal women recruited from 40 centers. Baseline questionnaires were used to collect sociodemographic and health status information. All CRC diagnoses were centrally adjudicated. Cox regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for invasive CRC by race/ethnicity. RESULTS: The study sample included 131,481 (83.7%) White, 14,323 (9.1%) African–American, 6,362 (4.1%) Hispanic, 694 (0.4%) Native American and 4,148 (2.6%) Asian/Pacific Islanders. After a mean follow-up of 10.8 years (SD 2.9), CRC incidence was the highest in African–Americans (annualized rate = 0.14%), followed by Whites and Native Americans (0.12% each), Asian/Pacific Islanders (0.10%), and Hispanics (0.08%). After adjustment for age and trial assignment, Hispanics had a lower risk compared with Whites, HR 0.73 (95% CI: 0.54–0.97) (P = 0.03), and African–Americans had a marginally greater risk, HR 1.16 (95% CI: 0.99–1.34), P = 0.06. Multivariable adjustment attenuated the difference in incidence between African–Americans and Whites (HR 0.99, 95% CI: 0.82–1.20), while strengthening the lower HR for Hispanics (HR 0.68, 95% CI: 0.48–0.97). CONCLUSIONS: African–American/White differences in CRC risk are likely due to sociodemographic/cultural factors other than race. IMPACT: A number of modifiable exposures could be a focus for reducing CRC risk in African–Americans