Participation of minorities in cancer research: the influence of structural, cultural, and linguistic factors.

Overall, participation rates in cancer clinical trials are very low, ranging from 3 to 20% of eligible participants. However, participation rates are especially low among the socially disadvantaged and racial/ethnic minority groups that have been historically underrepresented in clinical research. Structural factors such as study duration, treatment or intervention schedule, cost, time, followup visits, and side effects represent more of a barrier to participation among these groups compared with white, non-Hispanics. Attitudes, beliefs, perceptions, and knowledge regarding clinical research, and cultural characteristics of underrepresented minorities pose additional barriers to participation. This article focuses on the structural, cultural, and linguistic factors that affect participation in clinical cancer research for each major U.S. racial/ethnic group. Low socioeconomic status, speaking a primary language other than English, differences in communication styles, mistrust of research and the medical system, fear, embarrassment, and lack of knowledge about the origin of cancer appear to have a negative impact on clinical cancer research participation rates. Much of the information about these factors comes from studies of cancer screening because little data is available on the factors that prevent and facilitate participation of minorities in clinical cancer trials specifically. Such research is needed, and, given the heterogeneity within and between minority populations, should occur in several different geographic settings and with as many different minority subpopulations as possible.

Physician perspectives on increasing minorities in cancer clinical trials: an Eastern Cooperative Oncology Group (ECOG) Initiative.

PURPOSE: This paper describes the ECOG-NMA Minority Accrual Initiative to assure minority participation in cancer clinical trials. METHODS: Focus groups were held to identify physician-reported barriers to the enrollment of minority patients in Cleveland, OH, Indianapolis, IN, Santa Clara County, CA, and Philadelphia, PA. Community physicians affiliated with the National Medical Association (NMA), and Eastern Cooperative Oncology Group (ECOG) investigators participated in the focus groups. A four-step process consisting of focus group workshops were conducted to (i) identify barriers, (ii) develop potential solutions to the barriers, (iii) define solutions to barriers involving specific clinical trials, and (iv) implement the solutions. RESULTS: Focus group participants identified physician lack of information, patient fears and suspicion, the fear of losing patients, and distrust of the health care system as the major barriers to enrollment of African Americans. We found significant differences between community physicians and cancer program physicians in several areas. Community physicians emphasized personal contacts to address the lack of information and to overcome patient fears and suspicions, while the cancer program physicians emphasized printed materials. There was no difference by region in the barriers identified in the focus group workshops; however, the proposed solutions to overcoming the barriers were specific to each site. CONCLUSION: The four-step process developed by the ECOG and the NMA used the focus group methodology to identify and overcome barriers to participation of African Americans in cancer clinical trials. Outreach efforts to educate patients, their families, and community physicians about cancer clinical trials should be directed at overcoming patient suspicions and providing practical information to physicians about specific trials and how to enroll patients.

Combination versus sequential doxorubicin and docetaxel as primary chemotherapy for breast cancer: A randomized pilot trial of the Hoosier Oncology Group.

PURPOSE: To evaluate the efficacy and toxicity of combination and sequential dose-dense chemotherapy with doxorubicin and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) as primary chemotherapy of breast cancer. PATIENTS AND METHODS: Patients with newly diagnosed stage II or noninflammatory stage III breast cancer were randomly assigned to receive the same total doses of doxorubicin and docetaxel over a 12-week period before definitive surgery. Patients in arm A received sequential therapy with doxorubicin 75 mg/m(2) every 2 weeks for three cycles followed by docetaxel 100 mg/m(2) every 2 weeks for three cycles. Patients in arm B received combination therapy with doxorubicin 56 mg/m(2) plus docetaxel 75 mg/m(2) every 3 weeks for four cycles. Granulocyte colony-stimulating factor was administered on days 2 to 12 of each cycle in both groups. RESULTS: Forty patients were entered onto the trial. Pretreatment tumor size averaged 5.7 cm with clinically positive axillary lymph nodes in 23 patients (57%). As expected, myelosuppression was severe in both groups; however, >/= 80% of planned dose-intensity was delivered. Hand-foot syndrome was more common after sequential therapy. Clinical responses were similar in both groups, with an overall response rate of 87%, including 20% clinical complete remissions. Pathologic complete remission or residual in situ disease only was confirmed in five patients (12.8%). Patients who received sequential therapy had fewer positive lymph nodes (mean, 2.17 v 4.81; P <.037) at definitive surgery. CONCLUSION: Primary chemotherapy with doxorubicin and docetaxel is well tolerated and highly active. A sequential treatment schedule increases toxicity but may result in more substantial lymph node clearance than combination therapy.

Recruiting minority cancer patients into cancer clinical trials: a pilot project involving the Eastern Cooperative Oncology Group and the National Medical Association.

PURPOSE: Minority accrual onto clinical trials is of significant interest to cooperative oncology study groups. The Eastern Cooperative Oncology Group (ECOG) conducted a study to identify barriers and solutions to African American accrual onto clinical trials. METHODS: We hypothesize that the National Medical Association (NMA) might provide insight into ways to increase minority participation and that ECOG might facilitate that participation. Four sites were selected in which NMA chapters existed and ECOG main institutions with less than half of the corresponding percentage of minorities in their communities entered trials for 1992. Fifteen workshops were conducted using discussions and open-ended, self-administered questionnaires. RESULTS: Seventy percent of NMA physicians cited mistrust of the research centers, fear of losing patients, and a lack of respect from ECOG institutions as the most important barriers to minority cancer patient referrals, compared with 30% for ECOG physicians. Sixty-nine percent of NMA and 43% of ECOG physicians cited a lack of information about specific trials. Nearly half of NMA physicians (47%) cited a lack of minority investigators as a barrier, compared with 4% of ECOG physicians. Solutions by both groups were improved communication (73%) and culturally relevant educational materials (40%). ECOG physicians cited more minority outreach staff as a potential solution (22% v 6%). NMA physicians cited increased involvement of referring physicians (44% v4%). CONCLUSION: NMA physicians who serve a significant sector of the African American population demonstrated a willingness to participate and work with a cooperative group effort to increase participation of minority patients and investigators.

Promoting cancer screening among the first-degree relatives of breast and colorectal cancer patients: the design of two randomized trials.

BACKGROUND: In this paper two large nationwide trials are described, both of which will test a comparable telephone-based counseling intervention to promote cancer screening among the first-degree relatives (FDRs) of breast and colorectal cancer patients. The unit of randomization will be the family unit of eligible FDRs. Access to FDRs will be obtained from their relatives with cancer. Selected intervention and design issues are reviewed, including how both projects will respond to FDRs who exhibit significant levels of cancer-specific anxiety or distress and how potential high-risk cancer families will be accommodated. METHODS: Pursuant to the development of both studies, two feasibility surveys were conducted to determine whether patients would grant access to their FDRs and whether the FDRS identified by these patients would be receptive to the telephone intervention. RESULTS: Approximately 80% (106 of 132) of breast cancer patients agreed to provide access to their eligible FDRs when contacted on-site at participating hospitals and clinics. Of those subsequently selected for telephone follow-up (n = 95 or 90%), 80% (n = 76) were successfully contacted by telephone, and of these 97% (n = 74) provided the names and telephone numbers of their FDRs. Among colorectal cancer patients contacted on-site (n = 46), 96% (n = 44) agreed to provide access to their FDRs, and of those contacted by telephone (n = 33 or 75%), 91% (n = 30) provided the requested information about their FDRs. Once contacted, 95% of breast cancer FDRs (55 of 58) and 91% of colorectal cancer patients (51 of 56) endorsed the intervention strategy. CONCLUSIONS: It is argued that this intervention, if proven effective, could provide an exportable strategy for reaching large numbers of high-risk individuals to promote cancer screening.

A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy.

We performed a phase I trial of recombinant human interleukin-11 (rhIL-11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels of rhIL-11 (10, 25, 50, 75, and 100 micrograms/kg/d). rhIL-11 alone was administered by a daily subcutaneous injection for 14 days during a 28-day prechemotherapy "cycle 0." Patients (pts) subsequently received up to four 28-day cycles of cyclophosphamide (1,500 mg/m2) and doxorubicin (60 mg/m2) chemotherapy followed by rhIL-11 at their assigned dose (days 3 through 14). Sixteen pts (13 stage IV, 3 stage IIIB) were accrued to this study. Median age was 53 years and median Eastern Cooperative Oncology Group Performance Status was 0. A grade 3 neurologic event was seen in 1 pt at 100 micrograms/kg. Because of the degree of grade 2 constitutional symptoms (myalgias/arthralgias and fatigue) at 75 micrograms/kg, dose escalation was stopped and 75 micrograms/kg was the maximally tolerated dose. No other grade 3 or 4 adverse events related to rhIL-11 were seen. The administration of rhIL-11 was not associated with fever. Reversible grade 2 fatigue and myalgias/arthralgias were seen in all pts at 75 micrograms/kg. Weight gain of 3% to 5% associated with edema was seen at doses > 10 micrograms/kg but a capillary leak syndrome was not seen. rhIL-11 alone was associated with a mean 76%, 93%, 108%, and 185% increase in platelet counts at doses of 10, 25, 50, and 75 micrograms/kg, respectively. No significant changes in leukocytes were seen. A mean 19% decrease in hematocrit was observed. Acute-phase proteins increased with treatment at all doses. Compared with patients at the 10 micrograms/kg dose, patients receiving doses > or = 25 micrograms/kg experienced less thrombocytopenia in the first two cycles of chemotherapy. We conclude that rhIL-11 has thrombopoietic activity at all doses studied, is well tolerated at doses of 10, 25, and 50 micrograms/kg, and at doses > or = 25 micrograms/kg has the potential to reduce chemotherapy-induced thrombocytopenia in this model.

Eastern Cooperative Oncology Group studies of paclitaxel and doxorubicin in advanced breast cancer.

Based on their single-agent activity in metastatic breast cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and doxorubicin have been alternated and combined in Eastern Cooperative Oncology Group studies to identify a tolerable dose and schedule. A pilot trial in patients who had received no more than one prior chemotherapy regimen alternated paclitaxel 200 mg/m2 and doxorubicin 75 mg/m2 every 3 weeks. Seven of 12 patients had objective (complete plus partial) responses. A second (phase I) trial combined doxorubicin as an intravenous push and paclitaxel as a 24-hour continuous infusion. To evaluate the effect of the schedule on toxicity, the drug administration sequence (doxorubicin-->paclitaxel or paclitaxel-->doxorubicin) was alternated both between and within patients. initial doses were paclitaxel 150 mg/m2 and doxorubicin 50 mg/m2 in six patients, with a subsequent six patients receiving 175 and 60 mg/m2, respectively. Dose-limiting mucositis was seen at the second dose level when paclitaxel preceded doxorubicin, suggesting an important role for the administration sequence in determining toxicity (and possibly efficacy) in this regimen. These results support the sequence of doxorubicin 50 mg/m2 followed by paclitaxel 150 mg/m2 as the maximum tolerated dose. This combination has been incorporated as a treatment arm in an ongoing randomized prospective phase III Intergroup trial. By comparing the combination with both drugs as single agents (with crossover to the opposite agent at disease progression), investigators will attempt to assess response, toxicity, and time to progression as well as the degree of cross-resistance between the two agents. Given the poor prognosis of patients with advanced breast cancer, the three arms also will be evaluated in terms of patients' quality of life.

Paclitaxel (Taxol)/doxorubicin combinations in advanced breast cancer: the Eastern Cooperative Oncology Group experience.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the first taxane to enter routine clinical practice, has aroused considerable interest due to its novel mechanism of action and its significant activity in metastatic breast cancer. Given this activity, it seemed logical to attempt to combine paclitaxel with doxorubicin, the other most active single agent in metastatic breast cancer. The Eastern Cooperative Oncology Group performed two trials investigating paclitaxel/doxorubicin combinations in patients with advanced breast cancer in an attempt to identify a tolerable dose and schedule of the combination. In the first trial, paclitaxel and doxorubicin were alternated every 3 weeks in doses of 200 mg/m2 and 75 mg/m2, respectively, for patients who had received no more than one prior chemotherapeutic regimen. Therapy was well tolerated in this setting. At these doses, paclitaxel induced more granulocytopenia and less thrombocytopenia than did doxorubicin. Objective responses (complete and partial responses) were seen in seven of 12 patients; two other patients had improved disease (relief of pain in bony metastases). A second limited-institution Eastern Cooperative Oncology Group trial evaluated paclitaxel and doxorubicin given in combination. In this phase I trial, doxorubicin was given as an intravenous push and paclitaxel as a 24-hour continuous infusion. The sequence of drug administration (D-->P or P-->D) was alternated both between and within patients, so that we might evaluate the effect of administration schedule on toxicity. Therapy was begun at an initial paclitaxel dose of 150 mg/m2 and an initial doxorubicin dose of 50 mg/m2 in six patients, with a subsequent six patients receiving 175 and 60 mg/m2, respectively, of paclitaxel and doxorubicin. In addition, patients received granulocyte colony-stimulating factor 5 micrograms/kg/d. While therapy at the initial dose level was well tolerated, dose-limiting mucositis was seen at the second dose level, although only when paclitaxel preceded doxorubicin. This suggests that sequence of drug administration in paclitaxel-based regimens may play an important role as a determinant of toxicity and (perhaps) efficacy, a finding similar to that seen when paclitaxel and cisplatin were combined in patients with ovarian cancer. Based on this study, we identified the sequence of doxorubicin (50 mg/m2) followed by paclitaxel (150 mg/m2) to be the maximum tolerated dose. This combination is currently being compared with paclitaxel alone and doxorubicin alone in patients with advanced breast cancer in an intergroup trial led by the Eastern Cooperative Oncology Group.