Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer.

PURPOSE: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. PATIENTS AND METHODS: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m(2), with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m(2), for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2). Tamoxifen was given to 94% of patients with hormone receptor-positive tumors. RESULTS: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m(2), respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald chi(2) P =.0023; unadjusted Wilcoxon P =.0011) and 18% for death (adjusted P =.0064; unadjusted P =.0098). At 5 years, the disease-free survival (+/- SE) was 65% (+/- 1) and 70% (+/- 1), and overall survival was 77% (+/- 1) and 80% (+/- 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. CONCLUSION: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.

Increasing participation of minorities in cancer clinical trials: summary of the "Moving Beyond the Barriers" Conference in North Carolina.

A day-long seminar was held at Wake Forest University School of Medicine to address barriers among ethnic minorities in cancer clinical trials and explore ways that individuals who design and conduct clinical trials could increase minority representation. Speakers addressed implications of under-representation of minorities and identified barriers to minority participation. State-wide focus group results were presented and revealed suspicion of medical research among minorities and the need for bridging to minority communities to improve participation in cancer clinical trials. Working groups assembled and identified barriers specific to trial design, providers, and participants. Attendees were encouraged to devise strategies within their institutions to overcome barriers to minority participation.

Improving colorectal cancer screening by using community volunteers: results of the Carolinas cancer education and screening (CARES) project.

BACKGROUND: The goal of the Carolinas Cancer Education and Screening (CARES) Project was to improve colorectal cancer (CRC) screening among low-income women in subsidized housing communities in 11 cities in North and South Carolina who were traditionally underserved by cancer control efforts. METHODS: Cross-sectional samples were randomly selected from housing authority lists at 5 timepoints in this nonrandomized community-based intervention study. Face-to-face interviews focused on CRC knowledge, beliefs, barriers to screening, and screening behaviors. The intervention components were based on a previous evidence-based program. RESULTS: A total of 2098 surveys were completed. Seventy-eight percent of the respondents were African American, 62% were 65+ years, and 4% were married. At baseline, the rate of CRC screening within guidelines was 49.3% and physician recommendation was the strongest predictor (odds ratio [OR] = 21.9) of being within guidelines. There was an increase in positive beliefs about CRC screening (P = .010) and in the intention to complete CRC screening in the next 12 months (P = .053) after the intervention. The odds of being within CRC screening guidelines for women living in a city that had received the intervention were not significantly different from women living in a city that had not received the intervention (P = .496). CONCLUSIONS: Although CRC screening rates were not significantly better after the intervention, there was a positive change in beliefs about screening and intention to be screened. The results suggest that the dissemination of an evidence-based behavioral intervention may require a longer duration to engage hard-to-reach populations and change behaviors.

Medicine at the medical center then and now: one hundred years of progress.

The health and life expectancy of persons residing in the United States has improved dramatically during the 20th century. The average life span in the US has increased by more than 30 years since 1900. This significant gain is attributable to improvements in both public health and medical care. Tempering this notable achievement is the observation that the mortality rate per 1,000 population, although showing a significant decline in the era from 1920 to 1940, has now plateaued, and may be showing a slight increase. Our scientists and physicians have appropriately exploited the scientific discoveries of the 20th century and are poised as a medical tour de force for the 21st century. The decline in deaths from coronary artery disease and stroke has resulted from risk-factor modification and the innovations of surgeons and physicians who have dedicated themselves to early detection and better treatment of these cases. During the 1960s, patients admitted to our medical center with advanced Hodgkin's disease, hairy cell leukemia, and the acute leukemias had a life expectancy of < 1 year. Today, even advanced Hodgkin's disease and hairy cell leukemia are curable, and many patients with other acute leukemias respond to therapy and have very durable remissions. The rate of maternal mortality has shown a dramatic decline, and many childhood diseases have been eradicated or reduced to infrequent occurrences. Our public health scientists and physicians are joining forces to further diminish the morbidity and mortality rates for many of our common diseases. The achievements of our past afford us the vision for what we can become.

Long-term follow-up of a phase II trial studying a weekly doxorubicin-based multiple drug adjuvant therapy for stage II node-positive carcinoma of the breast.

BACKGROUND: Combination chemotherapy improves outcomes in women with breast cancer (BC) that involves axillary nodes. This single-arm study aimed to evaluate the effectiveness of an intensive doxorubicin-based multidrug regimen as adjuvant therapy in women with stage II, node positive breast cancer. PATIENTS AND METHODS: Between 7/80 and 8/85, 654 women, aged 25-73, who had a mastectomy for stage IIB BC were accrued. Patients with prior RT, chemotherapy, or surgical or radiation castration within 1 year of diagnosis were excluded. Treatment consisted of: 6 weekly courses of IV cyclophosphamide (C) 400 mg/m2, doxorubicin (A) 10 mg/m2, vincristine (V) I mg/m2, fluorouracil (F) 400 mg/m2, and a tapering course of prednisone followed by 12 courses of C 400 mg/m2, A 20mg/m2, V 1 mg/m2, F 400 mg/m2 given every 2 weeks. Patients with estrogen receptor positive tumors received Tamoxifen 10 mg bid between weeks 8 and 30. Treatment did not exceed 8 months. Median follow-up is 13.1 years. RESULTS: Six hundred thirty six patients are eligible. Fewer positive (+) nodes, premenopausal status, and positive progesterone receptor status are significantly (p < 0.05) associated with longer survival. At 10 years, 61% were relapse-free in the 1-3 +node group compared to 37 and 21% in the 4-9 and > or = 10 +node groups, respectively (p = 0.0001). Relapse-free survival at 10 years is 50% for premenopausal and 45% for postmenopausal patients. Severe or life-threatening hematological toxicity was seen in 6/630 (< 1%) patients. Four patients had severe (grade 3) neurotoxicity which resolved. No cardiac toxicity was observed. CONCLUSION: This adjuvant regimen compares favorably to other published adjuvant treatments with similar length of follow-up.

Clinical trial enrollment of rural patients with cancer.

PURPOSE: The goal of this study was to examine the effect of a rural community clinical oncology program-based cancer-care intervention program that was launched to increase the number of rural patients with cancer enrolled in clinical trials. DESCRIPTION OF STUDY: Five rural counties in eastern North Carolina served as intervention communities, and five rural counties in South Carolina served as the comparison region. The intervention counties used a rapid tumor-reporting system, a nurse facilitator who identified and prompted oncologists to enter patients into clinical trials, a quarterly newsletter to primary-care physicians about cancer treatment and clinical trials, and a health educator who focused on community-wide education regarding cancer prevention, treatment, and clinical trial information. Outcomes included changes in knowledge and attitudes about clinical trials among the primary-care providers who were surveyed and enrollment in clinical treatment trials for breast and colorectal cancer, as analyzed by comparing practice pattern data from before and after the intervention. RESULTS: The results indicate that the intervention was not effective. The proportion of primary-care physicians who were aware of clinical trials for their patients with cancer rose slightly in comparison counties (26% to 34%) but remained constant (41% to 43%) in intervention counties. Perceived patient and actual physician barriers toward clinical trial participation were reported by the physicians. A minority of potentially eligible patients with breast or colon cancer in both North Carolina and South Carolina were enrolled in clinical trials. CLINICAL IMPLICATIONS: These data suggest that different types of interventions may be needed to improve accrual to cancer treatment trials in rural communities. In addition, the role that primary-care providers play in encouraging patients with cancer to participate in clinical treatment trials needs further exploration.