First-In-Human Phase 1 Clinical Trials - A Single-Center Experience In The Era Of Modern Oncotherapeutics.

In the era of precision medicine the treatment options for cancer patients and subsequent outcomes are expected to improve. We present a review of patients enrolled in first-in-human Phase1 trials at University of Alabama at Birmingham. Between 1/2015-6/2017, 162 cancer patients (whole cohort, WC) were enrolled on phase1 studies receiving either targeted therapy (TT) or immuno-therapy (IOT). We assessed 90 day mortality (90DM) and time to treatment failure (TTF) to determine the predictors. Of the WC (122 (TT), 40 (IOT)), 90 (56%) received ≥ 2 prior therapies and 38 (24%) ⩾ 5 prior therapies. Overall, Grade 3 or 4 events were observed in 33% (WC) vs 31% (TT) vs 38% (IOT). The 90DM was 9.3% (WC) vs 7.4% (TT) vs 15% (IOT). The median TTF was 4.2 months vs 4.5 m vs 3.6 m. The number of lines of prior therapy and performance status were identified as outcome predictors. Our data reflects the new trend in precision oncology where majority received non-cytotoxic therapeutic interventions. The observation that number of lines of prior therapy and performance status predictive of PFS and 90DM emphasizes the need to consider phase1 trials earlier, preferably upon progression following definitive therapy.

Changes in complementary and alternative medicine use across cancer treatment and relationship to stress, mood, and quality of life.

OBJECTIVES: Complementary and alternative medicine (CAM) use is prevalent, but specific use of CAM across cancer treatment is underinvestigated. The objectives of this study were to assess changes in CAM use across cancer treatment; specific reasons for and satisfaction with specific types of CAM used; and associations of CAM use with stress, mood, and quality of life (QOL) in women with newly diagnosed breast cancer. DESIGN AND SETTING: Seventy-seven women with early-stage breast cancer who underwent active cancer treatment participated in the study. Data were collected three times: shortly after cancer diagnosis and 2 months and 6 months after the start of adjuvant cancer therapy. OUTCOME MEASURES: CAM Questionnaire, Impact of Event Scale (stress), Profile of Mood State (mood), and Functional Assessment of Cancer Therapy-Breast Cancer (QOL). RESULTS: Mean age was 52.4 years, and 94%-97% of women used on average five to six CAMs across three time points. Women largely started CAM use before cancer diagnosis and continued across cancer treatment. The five most common CAMs were prayer (88.3%), multivitamin use, massage, and vitamins E and C, followed by music, meditation, green tea, chiropractic care, and vitamin A, with little changes in types of CAM use across cancer treatment. Satisfaction was high, and satisfaction with prayer was the highest. Prayer, meditation, and music were used specifically for a feeling of control, whereas vitamins were used to improve the immune system, showing clear patterns. Stress, mood disturbance, and QOL declined significantly over time, p<0.001-0.04, but the number of CAMs used was unrelated to these variables. CONCLUSIONS: CAM use was highly prevalent with multiple CAMs and continued throughout cancer treatment. Prayer was the most common CAM; it had the highest satisfaction rating and the perception of being most helpful. The effect of long-term CAM use requires further investigation on psychological and biobehavioral outcomes with consideration of demographic and clinical characteristics.

Cancer-specific stress and mood disturbance: implications for symptom perception, quality of life, and immune response in women shortly after diagnosis of breast cancer.

Purpose. To determine the levels of cancer-specific stress and mood disturbance in women shortly after diagnosis of breast cancer and to assess their associations with symptom perception, quality of life, and immune response. Design. Descriptive and correlational. Sample and Setting. One hundred women with newly diagnosed breast cancer were recruited from interdisciplinary breast clinics. Methods. Baseline data were collected using standardized questionnaires and established bioassay prior to the initiation of cancer adjuvant therapy. Blood samples were collected about the same time of day. Results. High cancer-specific stress was significantly correlated with high mood disturbance, which, in turn, was correlated with high symptom perception, poor quality of life, and an immune profile indicating high neutrophils and low lymphocytes. Conclusions. High cancer-specific stress and related mood disturbance show extensive negative relationships with multiple behavioral, clinical, and biological factors. Implications for Nursing. Routine screening for cancer-related stress and mood disturbance should be incorporated into nursing practice for all patients diagnosed with cancer. Given broad negative associations with other biobehavioral factors, early identification of patients at risk and provision and evaluation of stress and mood management programs may have a beneficial effect on subsequent health outcomes over time.

Dose effects of relaxation practice on immune responses in women newly diagnosed with breast cancer: an exploratory study.

PURPOSE/OBJECTIVES: To determine the dose effects of relaxation practice on immune responses and describe the types of relaxation techniques preferred and the extent of relaxation practice over 10 months. DESIGN: Descriptive, prospective, repeated measures. SETTING: An interdisciplinary breast clinic at a university-affiliated comprehensive cancer center in the United States. SAMPLE: 49 women with newly diagnosed breast cancer and undergoing adjuvant therapy who participated in a stress management intervention. METHODS: Relaxation practice was assessed twice a month for 10 months with immune measurements (e.g., natural killer cell activity; lymphocyte proliferation; interferon [IFN]-γ; interleukin [IL]-2, -4, -6, and -10) at the beginning and end of 10-month practice. MAIN RESEARCH VARIABLES: Relaxation practice (representing the concepts of stress and adherence), relaxation technique, and immune response. FINDINGS: After adjusting for covariates, the extent of relaxation practice significantly contributed to the variance of natural killer cell activity, lymphocyte proliferation, IL-4, and IL-10 responses in a positive direction; the higher the relaxation practice, the higher the immune responses. In comparison, IFN-γ, IL-2, and IL-6 responses were not affected. The deep-breathing method was most preferred by participants, followed by progressive relaxation and imagination or visualization. The mean weekly frequency of relaxation practice was 5.29 (SD = 3.35), and the mean duration of relaxation practice was 19.16 (SD = 10.81) minutes per session. CONCLUSIONS: Persistent relaxation practice may have positive effects on multiple immune responses in a dose-dependent manner. IMPLICATIONS FOR NURSING: Allowing the choice of preferred techniques and emphasizing the importance of long-term adherence, a relaxation program may need to be routinely offered to women under high stress.

Significant impairment in immune recovery after cancer treatment.

BACKGROUND: Although immunosuppression from cancer adjuvant therapy has been documented, how these suppressed immune responses recover to baseline values after completion of cancer adjuvant therapy has not been studied systematically. OBJECTIVES: The objective of this study was to examine the probability of immune recovery after cancer adjuvant therapy and the potential impact of cancer adjuvant therapy type and cancer stage on immune recovery in patients with newly diagnosed breast cancer. METHODS: In a repeated-measures design, immune responses were measured four times in 80 patients with early-stage breast cancer: before and at 2, 6, and 12 months from the beginning of cancer adjuvant therapy. Natural killer cell activity, lymphokine-activated killer cell activity, lymphocyte proliferation, CD subsets (CD4, CD8, and CD56), and cytokines (interferon-gamma, interleukin [IL]-2, IL-4, IL-6, and IL-1alpha) were selected for their relevance to breast cancer. Immune recovery was defined by the level of immune response reaching to and above baseline levels. Data were analyzed using a multivariate generalized linear mixed-model approach. RESULTS: Delayed immune recovery to pretreatment baseline levels continued to the 12-month time point in all parameters. The percentages of immune recovery ranged from 6% to 76% of the patients, varying among immune parameters. Overall, immune recovery was poorer for interferon-gamma, IL-2, IL-4, lymphocyte proliferation, and natural killer cell activity than was for CD subsets and IL-6. The type of cancer adjuvant therapy, not cancer stage, showed selective influence on immune recovery. Chemotherapy or chemotherapy and radiotherapy combination significantly delayed IL-2 recovery, whereas radiotherapy significantly delayed IL-4 recovery. DISCUSSION: Immune recovery after breast cancer adjuvant therapy is delayed significantly for an extended time period in numerous immune parameters. The type of cancer adjuvant therapy has selective influence on immune recovery. Future investigations are warranted to elucidate the time course of immune recovery, clinical significance of poor immune recovery, and factors influencing immune recovery to develop potential interventions.