Relationship between phase I study duration and symptom burden.

PURPOSE: Phase I clinical trials are critical to development of cancer therapeutics. Adverse events (AEs) and symptom burden contribute to early treatment withdrawal, and it is often difficult to ascertain whether these events are disease- or treatment-related. Regardless, early withdrawal may delay determination of the effectiveness of potential new therapies. We sought to characterize the reasons for early treatment termination to identify potential modifiable events. METHODS: A retrospective chart review was conducted on solid tumor patients enrolled in institutional phase I clinical trials from 2003 to 2013 through the Case Comprehensive Cancer Center. RESULTS: Two hundred fifty-five patients were included in the analysis. The mean duration on study was 78.4 days (SD 63.4 days), and 23% of the patients were on study ≤ 30 days. Patients experienced an average of 25.1 AEs, of which 46.9% were non-laboratory. Constitutional symptoms (29.3%), gastrointestinal symptoms (24%), and pain (12.8%) were the most common non-laboratory AEs. Disease progression (57.6%) was the most common reason for study discontinuation, followed by adverse events (16.5%). Approximately 13% of the patients discontinued treatment for other reasons, of which 41.7% were identified as related to symptom burden on further review. Increased rates of AEs negatively correlated with duration on study (r = - 0.331; p < 0.01). CONCLUSIONS: AEs may lead to early termination of trial participation and confound clinical assessment of investigational treatments. Designing interventions to reduce AE burden may extend duration on trial, affect the recommended phase II dose, and benefit the quality of life of participants on phase I trials.

A randomized controlled trial of structured palliative care versus standard supportive care for patients enrolled in phase 1 clinical trials.

PURPOSE: Patients enrolled in Phase 1 clinical trials have typically exhausted standard therapies and often are choosing between a clinical trial and hospice care. Significant symptom burden can result in early trial discontinuation and confound trial outcomes. This study aimed to examine differences in study duration, symptom burden, adverse events (AE), and quality of life (QOL) between those receiving structured palliative care versus usual supportive care. PATIENTS AND METHODS: Sixty-eight patients enrolled in phase 1 clinical trials and 39 of their CGs were randomly assigned to receive structured palliative care or usual supportive care. Patient QOL was measured monthly using the Functional Assessment of Cancer Therapy and Memorial Symptom Assessment Scale. The Quality of Life in Life-Threatening Illness-Family Care Version and Caregiver Reaction Assessment were used for CGs. AEs and use of palliative care resources were compared between arms. RESULTS: Mean duration of the phase 1 study was 142 days in the palliative care arm versus 116 days in the usual care arm (p = 0.55). Although not statistically significant, patients in the palliative care arm experienced fewer AEs and better QOL, as did their CGs, compared to those receiving usual care. CONCLUSIONS: Phase 1 patients and their CGs have physical and psychosocial needs warranting palliative care services. Results suggest that structured palliative care is associated with the increased duration of the study and improved patient and CG QOL.

A pilot study of a low glycemic load diet in patients with stage I-III colorectal cancer.

BACKGROUND: Consumption of a diet with high glycemic indices has been associated with inferior cancer-specific outcomes in patients with early-stage colorectal cancer, but there is limited prospective evidence that alterations in dietary habits improves cancer outcomes. This study aimed to determine the feasibility and acceptability of following a low glycemic load (GL) diet in patients with stage I-III colorectal cancer. METHODS: Patients with stage I-III colorectal cancer, who completed definitive therapy, and consumed an average daily GL >150 participated in a 12-week tailored face-to-face dietary intervention with a target GL. This study followed a 2-stage design, with 4 planned cohorts, each with an assigned GL target and dietary intervention intensity. The primary endpoint of feasibility was determined by participant compliance, defined as an individual following the assigned GL ≥75% of the time. Compliance was determined using 24-hour telephone recalls. A cohort was deemed feasible if at least 67% of participants were compliant. Secondary endpoints included acceptability of the diet, nutritional support resources necessary to follow the diet, and evaluation of the effect of the diet on physical measures and correlative laboratories. RESULTS: Only cohort 1 was required as the primary endpoint of feasibility was met (stringent GL target, low intensity dietary support). The majority of participants experienced a decrease in body mass index (BMI) and waist circumference, 29% experiencing meaningful weight loss (≥5%). The dietitian spent an average of 6.97 hours (SD 2.18) face-to-face time and 1.58 hours (SD 0.68) by phone with each participant. Significant decreases were seen in total cholesterol, very-low-density lipoprotein (VLDL) and triglycerides (all P<0.05). All participants liked the foods and were satisfied with the diet. All participants felt the in-person meetings were helpful, and 62% did not feel a virtual meeting (e.g., Skype, etc.) could replace in-person meetings. CONCLUSIONS: Patients with stage I-III colorectal cancer can follow a low GL diet with a 12-week in-person dietary intervention. Significant changes in physical and laboratory measures suggest relevant biologic effects of the dietary intervention. This study establishes feasibility, and warrants a larger scale prospective intervention trial to evaluate the impact of a low GL diet on cancer outcomes.

Pembrolizumab-Induced Immune-Mediated Colitis in a Patient with Concurrent Clostridium Difficile Infection.

Pembrolizumab is a programmed death receptor-1 (PD-1) inhibitor that has been approved for treatment of a wide variety of malignancies. Immune-mediated colitis is a known but uncommon adverse effect of pembrolizumab. Symptoms of immune-mediated colitis can be similar to those of many other gastrointestinal illnesses, including Clostridium difficile infection (CDI). If not recognized and treated in a timely fashion, immune-mediated colitis can lead to significant morbidity in cancer patients. We report the case of a 56-year-old woman on pembrolizumab for metastatic non-small cell lung cancer (NSCLC) who presented with severe colitis symptoms and initially tested positive for CDI. Her colitis symptoms worsened despite appropriate treatment for CDI but later improved rapidly after systemic corticosteroid was started for suspected immune-mediated colitis. To our knowledge, this is the first reported case of concurrent pembrolizumab-induced colitis and CDI. Immune-mediated colitis should be considered in the differential diagnoses in patients on pembrolizumab or other immune checkpoint inhibitors who present with colitis symptoms, even when a concurrent infectious etiology is suspected.

Vancomycin-resistant enterococci infection: not just for the transplanted.

Vancomycin-resistant enterococcal (VRE) blood stream infections (BSIs) pose significant hazards to patients with hematologic malignancy. We compared and examined VRE BSI rates, patient characteristics and clinical outcomes for two cohorts of patients: those who did and did not undergo hematopoietic cell transplant (HCT). In this single institution study, we retrospectively analyzed records of consecutive patients from 1998 through 2011. Over this 14-year period, VRE was identified in 14% of all BSIs in patients with HCT with a cumulative rate of 1.9% (48/2581 BSIs/patients). VRE was identified in 10% of all BSIs in non-HCT patients with a cumulative rate of 1.1% (35/3154 BSIs/patients). Transplant patients who developed VRE BSI tended to be younger, hospitalized more frequently, were exposed to vancomycin therapy frequently, and were more likely to have had a central venous catheter removed. VRE remains a significant cause of morbidity and mortality, as 22 deaths were directly or indirectly attributed to this infection. Both HCT and non-HCT patients are susceptible to VRE infection and are equally at risk for adverse outcomes related to VRE BSI.