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Biomedical subjects

Archie Bleyer

Publications and source records attributed to Archie Bleyer.

13 recordsLinked to original sources

Assessing the health care needs of adolescent and young adult cancer patients and survivors.

BACKGROUND: Improvements in cancer outcomes observed for the United States population as a whole are not experienced as such by adolescent and young adult (AYA) patients. The objective of this study was to identify important health and supportive care needs for AYA patients and survivors. METHODS: Forty oncology health professionals and 37 young adults (ages 18 years to 44 years; diagnosed between ages 15 years and 39 years) participated on a modified Delphi panel. Over 3 iterative rounds of mailed surveys, participants identified, rank ordered, and rated the importance of various items. RESULTS: Overall, there was general agreement among health care providers and young adult survivors, with some notable exceptions. Providers and young adult survivors agreed on the relative importance of having adequate health insurance and oncology care that addresses the unique developmental characteristics of this population. Compared with health professionals, young adults ranked the importance of opportunities to meet other young adult survivors at a relatively higher level, and they also ranked those opportunities higher than the importance of support from family and friends. CONCLUSIONS: These findings provide oncology professionals and young adults with insight into the others' values and perspectives. These findings also suggest areas in which to target investments of resources to promote quality health care and appropriate informational and supportive care services and to overcome the deficit in survival improvement that has occurred in young adults and older adolescents with cancer.

Adolescent↗

Adolescents and young adults with cancer: the scope of the problem and criticality of clinical trials.

In the U.S., older adolescents and young adults with cancer have benefited less from therapeutic advances than did either younger or older patients. One factor that may explain this deficit is the relative lack of participation of patients in this age group on clinical trials of therapies that could improve their outcome. Comparisons were made of the participation of cancer patients on clinical trials in the U.S., as a function of patient age, with the change in national cancer mortality rate; and Surveillance, Epidemiology, End Results (SEER) cancer survival rate as a function of age. The participation rate in cancer treatment trials has been strikingly lower in 15-34-year-olds than in younger or older patients. The nadir has been apparent for both males and females in all of the major ethnic and racial groups. The national cancer mortality reduction and SEER survival improvement shows a similar age dependence. In the U.S., the age-dependence of cancer treatment trial participation, and of improvement in survival prolongation and cancer death rates, are correlated. Regardless of whether there is a causal relationship, the impact on the older adolescent and young adult U.S. population is substantial, adversely affecting the national cost of healthcare, the person-years of life lost, the loss of young people entering the job market, and the scientific knowledge and social implications of cancer during adolescence and early adulthood. National initiatives are underway to address these issues, with special emphasis on increasing the availability and access to clinical trials designed for older adolescents and young adults.

Adolescent↗

Proceedings of a workshop: bridging the gap in care and addressing participation in clinical trials.

The purpose of this workshop was to examine possible strategies for increasing participation by adolescent and young adult cancer patients in clinical trials. Three key established issues set the framework for this discussion: 1) In the United States, individuals in the 15-40 age group are less likely than either children or older adults to be referred to a comprehensive cancer center. 2) Enrollment in therapeutic clinical trials is unacceptably low among adolescent and young adult patients everywhere this has been studied, including United States, Canada, and United Kingdom. 3) Cancers that occur in patients in this age group with particular frequency (notably malignant lymphomas and bone tumors) have relatively long intervals from symptom onset to diagnosis (POG 9082). This may reflect both distinct biologic features of these diseases and a real gap in health care.

Adolescent↗

A multi-center phase II study of sequential paclitaxel and bryostatin-1 (NSC 339555) in patients with untreated, advanced gastric or gastroesophageal junction adenocarcinoma.

PURPOSE: Protein Kinase C (PKC), involved in transmembrane signaling of cell surface receptors, promotes carcinogenesis and tumor progression. Bryostatin-1 competes with PKC for phorbol esters (tumor promoters), thus inhibiting tumor progression. Bryostatin-1 also increases cytotoxicity of paclitaxel in a sequential fashion. We studied sequential paclitaxel and bryostatin-1 in patients with untreated, advanced gastric adenocarcinoma. METHODS: Patients with histologic proof of gastric or gastroesophageal junction adenocarcinoma with advanced, measurable cancers were eligible. Patients were required to have near normal organ function and ECOG performance status of 0 or 1. All patients gave an informed consent. Patients received paclitaxel 80 mg/m2 in 2 h intravenously on day 1 and bryostatin-1 40 mcg/m2 in 1 h intravenously on day 2 each week for 3 consecutive weeks out of 4. Primary objective was to assess the objective response rate. RESULTS: In a multi-center setting, 37 patients were enrolled and 35 were assessable for response. A confirmed partial response rate was 29%. The median time-to-progression was 4.25 months and the median survival time was 8 months. Grade 3 cumulative myalgias occurred in 55% of patients. Twelve patients discontinued therapy due to myalgias, including 6 patients who had not progressed after achieving a partial response. Other toxic effects were uncommon. CONCLUSIONS: Sequential paclitaxel plus bryostatin-1 resulted in a superior response rate than would be expected of paclitaxel alone in patients with untreated, advanced gastric or gastroesophageal junction adenocarcinoma. Further development of this combination is warranted once an effective method to ameliorate or prevent myalgias can be established.

Adenocarcinoma↗

Cancer in 15- to 29-year-olds by primary site.

INCIDENCE: Cancer occurring between the ages of 15 and 30 years is 2.7 times more common than cancer occurring during the first 15 years of life, yet is much less common than cancer in older age groups, and accounts for just 2% of all invasive cancer. Cancer in adolescents and young adults is unique in the distribution of the types that occur. Hodgkin lymphoma, melanoma, testis cancer, female genital tract malignancies, thyroid cancer, soft-tissue sarcomas, non-Hodgkin lymphoma, leukemia, brain and spinal cord tumors, breast cancer, bone sarcomas, and nongonadal germ cell tumors account for 95% of the cancers in this age group. The frequency distribution of cancer types changes dramatically from age 15-30, such that the pattern at the youngest age does not resemble the one at the oldest. The incidence of cancer in this age group increased steadily during the past quarter century. This increase is declining and at the older end of the age range appears to be returning to the incidence of the 1970s. Males in the 15- to 29-year age group have been at higher risk of developing cancer, with the risk directly proportional to age. Non-Hispanic whites have had the highest risk of developing cancer during this phase of life, and Asians, American Indians and Native Alaskans the lowest. Males had a worse prognosis than females. African-Americans, American Indian/Alaska Natives had a worse prognosis than white non-Hispanics and Asians. MORTALITY & SURVIVAL: At the beginning of the last quarter century, the diagnosis of cancer in 15- to 29-year-olds carried a more favorable prognosis, on the average, relative to cancer at other ages. Since then, there has been a lack of progress in survival improvement among older adolescents and young adults relative to all other ages. Survival improvement trends portend a worse prognosis for young adults diagnosed with cancer today than 25 years ago. The survival deficit is increasing with longer follow-up of the survivors, and is worse in males. Among 15- to 29-year-olds, non-Hispanic whites had the best survival and African Americans/blacks had the worst survival, with a 20% difference apparent by 5 years. Asians/Pacific Islanders had the second best survival, with Hispanics and American Indians/Alaska Natives next in sequence. RISK FACTORS: In general, there are relatively scant data to support either an environmental causation or an inherited predisposition to cancer in this age group. The majority of cases of cancer occurring before age 30 appear to be spontaneous and unrelated to either carcinogens in the environment or family cancer syndromes. Overall, family cancer syndromes appear to account for less than 5% of the cases of cancer in the age group. Melanoma, cervical carcinoma and Kaposi sarcoma, non-Hodgkin lymphoma, Hodgkin and Burkitt lymphomas accounting for the majority of environmentally induced malignancies (ultraviolet light, human papillomavirus, human immunodeficiency virus, and Epstein-Barr virus, respectively). Ultimately, a larger proportion of cases may be attributable to specific factors or genetic predisposition, but at present, most cancer in this age group appears to be sporadic and random.

Adolescent↗

Are experimental treatments for cancer in children superior to established treatments? Observational study of randomised controlled trials by the Children's Oncology Group.

OBJECTIVES: To assess how often new treatments for childhood cancer assessed in phase III randomised trials are superior or inferior to standard treatments and whether the pattern of successes and failures in new treatments is consistent with uncertainty being the ethical basis for enrolling patients in such trials. DESIGN: Observational study. SETTING: Phase III randomised controlled trials carried out under the aegis of the Children's Oncology Group between 1955 and 1997, regardless of whether they were published. MAIN OUTCOME MEASURES: Overall survival, event free survival, and treatment related mortality. RESULTS: 126 trials were included, involving 152 comparisons and 36,567 patients. The odds ratio for overall survival with experimental treatments was 0.96 (99% confidence interval 0.89 to 1.03), indicating that new treatments are as likely to be inferior as they are to be superior to standard treatments. This result was not affected by publication bias, methodological quality, treatment type, disease, or comparator. CONCLUSIONS: New treatments in childhood cancer tested in randomised controlled trials are, on average, as likely to be inferior as they are to be superior to standard treatments, confirming that the uncertainty principle has been operating.

Child↗

Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma.

BACKGROUND: Oxaliplatin is a platinum derivative with a broad range of anticancer activity. The objective of the current Phase II trial was to investigate the activity of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma (NHL). METHODS: Patients with recurrent and refractory NHL who received a maximum of 3 previous chemotherapy regimens were considered eligible if they had an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Oxaliplatin was administered in an outpatient setting at a dose of 130 mg/m(2) by 2-hour intravenous infusion every 21 days for < or = 6 cycles in the absence of disease progression. RESULTS: Thirty-one patients (23 with aggressive NHL and 8 with indolent NHL) were enrolled, of whom 30 were assessable for toxicity, response, and survival. The median patient age was 62 years, and 20% of the patients previously received platinum-containing therapy. Eighty-three percent of the patients were refractory to their last treatment regimens. Grade 3 and 4 toxic effects (according to the National Cancer Institute's Common Toxicity Criteria [version 2.0]) included sensory neuropathy (10%), neutropenia (17%), and thrombocytopenia (20%). Objective responses occurred in 8 (27%; 95% confidence interval, 13-47%) of the patients. Responses were observed in platinum-naive patients as well as in those previously treated with platinum. The overall median failure-free survival duration was 3.0 months (range, 0.1-18.1 months). CONCLUSIONS: Oxaliplatin had favorable single-agent activity in previously treated patients with refractory lymphoma. The favorable safety profile and the ease of its administration in outpatient settings warrant investigating it in combination with other active drugs for the treatment of recurrent and refractory NHL.

Adult↗

National survival trends of young adults with sarcoma: lack of progress is associated with lack of clinical trial participation.

BACKGROUND: Young adults with cancer in the U.S. have had less improvement in survival than either younger patients or older patients. The authors attempted to determine whether similar deficits have occurred in young adults with sarcomas and, if so, then why. METHODS: In 38,144 young adults with sarcoma who were diagnosed during 1975-1998 and were followed by the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results Program, the average annual percent change in 5-year survival was derived as a function of patient age. National sarcoma treatment trial data were obtained on 3242 patients who were entered onto NCI-sponsored trials during 1997-2002. RESULTS: 1) For patients with bone and soft-tissue sarcomas, except Kaposi sarcoma (KS), the least survival improvement occurred between age 15 years and age 45 years. For patients with KS, the pattern was reversed, with the greatest survival increase occurring among patients ages 30-44 years. 2) The lowest participation rate in NCI-sponsored sarcoma treatment trials occurred in patients ages 20-44 years. For patients with KS, the highest accrual rate occurred in patients ages 35-44 years. 3) The age-dependent survival improvement and clinical-trial accrual patterns were correlated directly (soft-tissue sarcomas, P < 0.005; bone sarcomas, P < 0.05; KS, P = 0.06), regardless of whether the accrual profile demonstrated a decline or a peak (KS) during early adulthood. CONCLUSIONS: The lack of survival prolongation in patients age 15-44 years in the U.S. with non-KS sarcomas may have been a result of their relative lack of participation in clinical trials. If this is true, then reversing the shortfall in survival among young adults with sarcomas, as was accomplished among patients with KS, should benefit from increased clinical trial availability, access, and participation.

Adolescent↗

Older adolescents with cancer in North America deficits in outcome and research.

In the two decades from the mid 1970s to the mid 1990s, the proportion of 5-year survivors among children in North America with cancer has increased nearly 40%. Advances in otherwise fatal leukemias, lymphomas, sarcomas, brain tumors, germ cell neoplasms and cancer of the kidney account for much of the improvement. Unfortunately, older adolescents have not fared as well. Their epidemiological, medical, physical, psychological and social needs remain largely unmet despite their age juxtaposition with younger patients whose outcomes have so much improved. In the United States and Canada, cancer in adolescents 15 to 19 years of age occurs at nearly twice the rate observed in 5 to 14 year-olds. Many of the types of cancer that occur in older adolescents are unique to this age group, and the pattern of distribution occurs at no other age interval. Overall, the cancers in older adolescents are more similar to the spectrum of cancer in children than to the common types of cancer in adults, but they are also distinctly different and require an age-specific approach. There is evidence of a lower degree in reduction in cancer mortality in the United States and Canada in this age range than in younger or older persons. Moreover, the disparity appears to be increasing. The improvement in 5-year survival from diagnosis of cancer from the mid 1970s to the early 1990s was lower than the rate of improvement in the younger age groups. Survival rates of older adolescents with cancer in the general population have not improved as much, especially in comparison with results of the national pediatric cooperative cancer groups. In the United States and Canada, only about 5% of 15 to 25 year-olds with cancer are entered onto clinical trials, in contrast to 60% to 65% of younger patients. Thus, cancer during adolescence and early adulthood has been relatively neglected and merits enhanced national research programs and resources.

Adolescent↗